The outbreak of SARS-CoV-2 infection has presented the world with an urgent demand for advanced diagnostics and therapeutics to prevent, treat and control the spread of infection. Nanotechnology seems to be highly relevant in this... more
The outbreak of SARS-CoV-2 infection has presented the world with an urgent demand for advanced diagnostics and therapeutics to prevent, treat and control the spread of infection. Nanotechnology seems to be highly relevant in this emergency due to the unique physicochemical properties of nanomaterials which offer versatile chemical functionalization to create advanced biomedical tools. Here, nano-intervention is discussed for designing effective strategies in developing advanced personal protective equipment kits, disinfectants, rapid and cost-effective diagnostics and therapeutics against the infection. We have also highlighted the nanoparticle-based vaccination approaches and how nanoparticles can regulate the host immune system against infection. Overall, this review discusses various nanoformulations that have shown clinical relevance or can be explored in the fight against COVID-19.
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Pancreatic cancer is considered as one of the most lethal type of cancer with a poor 5-year survival rate. Cancer metastasis represents one of the primary cause which limits therapy against this disease. Current chemotherapeutic... more
Pancreatic cancer is considered as one of the most lethal type of cancer with a poor 5-year survival rate. Cancer metastasis represents one of the primary cause which limits therapy against this disease. Current chemotherapeutic approaches are largely ineffective, thus calling for the development of alternative strategies to combat this disease. In this regard, numerous studies have reported the anticancer effect of curcumin in different types of cancer including pancreatic cancer. However, low aqueous solubility, poor stability and decreased bioavailability associated with native curcumin holds back its use in clinical settings. In order to enhance its therapeutic value, polymeric nanoparticles (NPs) represent an ideal delivery system. Further, surface modification of NPs with various macromolecules, such as chitosan and polyethylene glycol (PEG) holds tremendous potential for improving the bioavailability and circulation time of native drug in the blood. In the present study, we h...
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Tumors are heterogeneous and contain a small population of cells that has a crucial role in tumor progression, metastasis, drug resistance, and relapse as a result of their self-renewal, proliferation, and differentiation properties.... more
Tumors are heterogeneous and contain a small population of cells that has a crucial role in tumor progression, metastasis, drug resistance, and relapse as a result of their self-renewal, proliferation, and differentiation properties. These cells are known as cancer stem cells (CSCs) and accumulating evidence suggests that they show significant resistance to conventional chemotherapy. Thus, various antitumor strategies have been developed to eliminate therapeutic-resistant CSCs by targeting the molecular differences between CSCs and bulk cancer cells. Here, we highlight the use of nanomedicine-mediated dual drug delivery to target CSCs and bulk cancer cells simultaneously. We also summarize current prospects and challenges associated with this therapy.
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Research Interests: Biomaterials, Cell Cycle, Cytotoxicity, Apoptosis, Pancreatic Cancer, and 15 moreMultidisciplinary, Western blotting, Cell line, Humans, Mice, Female, Animals, Animal Model, Bioavailability, Food and Drug Administration, Clinical Application, Chemical Modification, Low molecular weight, Dna Synthesis, and Pancreatic neoplasms
Brain diseases are the most serious health problems; represent a significant and worldwide public health problem. Small interfering RNAs (siRNAs) can initiate specific silencing of genes and are potential therapeutic agents for many... more
Brain diseases are the most serious health problems; represent a significant and worldwide public health problem. Small interfering RNAs (siRNAs) can initiate specific silencing of genes and are potential therapeutic agents for many genetically influenced diseases including brain disease. However, on systemic administration the blood-brain barrier (BBB) poses most significant obstacle for the therapeutic siRNAs delivery to the brain. Therefore, the development of successful approaches to enhance siRNA delivery to the brain is of immense interest in clinical and pharmaceutical research. At present, intranasal delivery approach serves as an effective mode of direct delivery of siRNAs to brain by bypassing BBB. In this review, we describe the principles of RNA interference (RNAi) machinery; challenges associated with siRNAs in therapeutics brain targeting and summarize the recent progress made in the use of vector based siRNA technology. Further, it is anticipated that intranasal delivery approach will have a very important role to play in the future for the translation of siRNAs therapeutics from bench to bedside for different brain diseases.
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Mesenchymal stem cells (MSCs) have gained much interest to be used as targeting vehicle in cancer therapy due to the intrinsic tumor-homing behavior associated with them. In this scenario, superparamagnetic nanoparticles are emerging as... more
Mesenchymal stem cells (MSCs) have gained much interest to be used as targeting vehicle in cancer therapy due to the intrinsic tumor-homing behavior associated with them. In this scenario, superparamagnetic nanoparticles are emerging as an ideal probe for noninvasive cell tracking for different stem cell applications. In the study, it is demonstrated that the formulated aqueous dispersible glyceryl monooleate coated magnetic nanoparticles (MNPs) can act as a better labeling and efficient tracking agent without affecting the inherent properties of MSCs. The MNPs-MSCs facilitate the stem cell tracking by magnetic resonance imaging at a very low cell number having high T2 relaxivity and potentiates the use of MNPs-MSCs as a prospective diagnostic tool. Most importantly, the homing of MNPs-MSCs toward inflammation site, subcutaneous prostate tumor (small as well as large tumor), and in orthotopic prostate tumor suggests the clinical relevance of the system. In addition, intraperitoneal delivery of MNPs-MSCs shows enhanced tumor accumulation and less sequestration in liver as revealed by in vivo imaging and histological studies. The results here demonstrate that MNPs-MSCs may prove as a better targeted delivery agent for early diagnosis of tumors even of smaller size.
Combination therapy in cancer is now opted as a potential therapeutic strategy for cancer treatment. However, effective delivery of drugs in combination at the tumor site is marred by low bioavailability and systemic toxicity of... more
Combination therapy in cancer is now opted as a potential therapeutic strategy for cancer treatment. However, effective delivery of drugs in combination at the tumor site is marred by low bioavailability and systemic toxicity of individual drugs. Polymer therapeutics is indeed an upcoming approach for the combinational drug delivery in favor of better cancer management. Hence, the objective of our investigation was to develop a dual drug PEGylated system that carries two chemotherapeutic drugs simultaneously for effective treatment of cancer. In this regard, we have synthesized Pem-PEG-Gem, wherein pemetrexed (Pem) and gemcitabine (Gem) are conjugated to a heterobifunctional polyethylene glycol (PEG) polymer for the effective treatment of Non-Small Cell Lung Cancer (NSCLC). Our results demonstrate enhanced bioavailability of the individual drugs in Pem-PEG-Gem in comparison with the drugs in their native form. The developed Pem-PEG-Gem showed enhanced cell death with respect to their native counterparts when treated singly or in combination against NSCLC cells. This might be attributed to better cellular internalization through the process of macropinocytosis and synergistic cytotoxic action of Pem-PEG-Gem in NSCLC cells. Hence, we propose the above dual drug based polymer therapeutic approach suitable for better clinical application in the treatment of NSCLC.
Research Interests: Cytotoxicity, Pharmaceutical Chemistry, Humans, Animals, Cell Death, and 11 moreBioavailability, High Pressure Liquid Chromatography, Fourier transform infrared spectroscopy, Pharmaceutical Formulation Technology, Drug Carriers, Biological Availability, Polyethylene Glycols, proton magnetic resonance spectroscopy, Drug synergism, Pharmacology and pharmaceutical sciences, and lung neoplasms
Nowadays, emerging aspects of cancer therapy involve both diagnostic and therapeutic modules in a single setting. Targeted theranostic nanoplatforms have emerged globally as frontier research for the improvement of cancer therapy.... more
Nowadays, emerging aspects of cancer therapy involve both diagnostic and therapeutic modules in a single setting. Targeted theranostic nanoplatforms have emerged globally as frontier research for the improvement of cancer therapy. Trastuzumab (Tmab), a humanized monoclonal antibody is now being used to target human epidermal growth factor receptor-2 (HER 2) positive cancer cells. In the present study, we have analysed the imaging and theragnosis potentiality of Tmab functionalized lipid based nanoparticles (NPs) loaded with anticancer drug rapamycin and imaging agent (quantum dots) for targeted cancer therapy and imaging. The therapeutic evaluation of drug loaded NPs were evaluated through various in vitro cellular studies. The results showed enhanced therapeutic efficacy of targeted drug loaded NPs over native drug and unconjugated NPs in HER 2 positive SKBR 3 breast cancer cell line. Moreover, exploration of the therapeutic benefits of rapamycin loaded Tmab conjugated NPs (Tmab-rapa-NPs) at molecular level, revealed augmented down regulation of mTOR signalling pathway thereby, inducing more cell death. Above all, our targeted multifunctional NPs have shown an excellent bio-imaging modality both in 2D monolayer and 3D tumor spheroid model. Thus, we can anticipate that such a multimodal nanotheranostic approach may be a useful tool for better cancer management in future.
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The intricate problems associated with the delivery and various unnecessary in vivo transitions of proteins and drugs needs to be tackled soon to be able to exploit the myriad of putative therapeutics created by the biotechnology boom.... more
The intricate problems associated with the delivery and various unnecessary in vivo transitions of proteins and drugs needs to be tackled soon to be able to exploit the myriad of putative therapeutics created by the biotechnology boom. Nanomedicine is one of the most promising applications of nanotechnology in the field of medicine. It has been defined as the monitoring, repair, construction and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. These nanostructured medicines will eventually turn the world of drug delivery upside down. PEGylation (i.e. the attachment of polyethylene glycol to proteins and drugs) is an upcoming methodology for drug development and it has the potential to revolutionise medicine by drastically improving the pharmacokinetic and pharmacodynamic properties of the administered drug. This article provides a total strategy for improving the therapeutic efficacy of various biotechnological products in d...
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Nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactide) (PLA) are being extensively investigated for different therapeutic applications such as for sustained drug, vaccine, and gene delivery. For many of... more
Nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactide) (PLA) are being extensively investigated for different therapeutic applications such as for sustained drug, vaccine, and gene delivery. For many of these applications, it is necessary to study the intracellular distribution as well as the tissue uptake of nanoparticles to optimize the efficacy of the encapsulated therapeutic agent. Fluorescence and electron microscopic techniques are usually used for the above purposes. Colloidal gold particles and fluorescent polystyrene, which are generally used as model particles for electron and fluorescence microscopy, respectively, may not be suitable alternatives to PLGA/PLA nanoparticles for these studies mainly because of the differences in their physical properties and also because they do not contain any therapeutic agent. The aim of the present study was to develop and characterize PLGA nanoparticle formulations that would be suitable for confocal/fluorescence and transmission electron microscopic (TEM) studies. Towards this objective, PLGA nanoparticles containing 6-coumarin as a fluorescent marker and osmium tetroxide as an electron microscopic marker with bovine serum albumin (BSA) as a model protein were formulated. Different physical properties of marker-loaded nanoparticles such as particle size, zeta potential, residual PVA content and protein-loading were compared with those of unloaded nanoparticles and were found to be not significantly different. Furthermore, marker-loaded nanoparticle formulations were non-toxic to the cells as unloaded nanoparticles. Nanoparticles loaded with 6-coumarin were found to be useful for studying intracellular nanoparticle uptake and distribution using confocal microscopy while osmium tetroxide-loaded nanoparticles were found to be useful for studying nanoparticle uptake and distribution in cells and tissue using TEM. It was concluded that 6-coumarin and osmium tetroxide could serve as useful fluorescence and electron microscopy probes, respectively, for incorporation into nanoparticles to study their cellular and tissue distribution.
Research Interests: Electron Microscopy, Fluorescence Microscopy, Transmission Electron Microscopy, Nanotechnology, Confocal Microscopy, and 13 morePolymers, Pharmaceutics, Humans, Biodegradable Polymers, Coumarins, Particle Size, Time Factors, Bovine Serum Albumin, Polyesters, Drug Carriers, Lactic Acid, fluorescent dyes, and Pharmacology and pharmaceutical sciences
Over expression of drug efflux transporters such as P-glycoprotein (P-gp) cumulatively leading to multidrug resistance (MDR) embodies a major hindrance for successful cancer therapy. A paradigm nanomedicinal approach involving an... more
Over expression of drug efflux transporters such as P-glycoprotein (P-gp) cumulatively leading to multidrug resistance (MDR) embodies a major hindrance for successful cancer therapy. A paradigm nanomedicinal approach involving an anticancer drug and modulators of drug resistance within one multifunctional nanocarrier-based delivery system represent an ideal modality for the treatment of MDR. In this regards, we have developed a cationic polymeric nanoparticulate system loaded with MDR1-siRNA and doxorubicin. Results indicated augmented synergistic effect of combinational nanoformulation in overcoming MDR in MCF-7/ADR cells. Therefore, the above regime could be a promising co-delivery system for effective therapy of drug resistant breast cancer.
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The rapid clearance of circulating nanoparticles from the blood stream coupled with their high uptake by liver and spleen has thus far been overcome by reducing the particle size, and by making the particle surface hydrophilic with... more
The rapid clearance of circulating nanoparticles from the blood stream coupled with their high uptake by liver and spleen has thus far been overcome by reducing the particle size, and by making the particle surface hydrophilic with poloxamers and poloxamines. We have prepared hydrogel nanoparticles of polyvinylpyrrolidone of a size less than 100 nm diameter with precise size distribution. Since the inner cores of these particles are also hydrophilic, these particles are capable of encapsulating water-soluble compounds. Biodistribution of these particles shows practically negligible (<1%) uptake by the macrophages in liver and spleen, and approximately 5-10% of these particles remain in circulation even 8 h after i.v. injection. Increasing the surface hydrophobicity as well as particle size can increase the RES uptake of these particles. Because of longer residence in blood, the hydrogel nanoparticles have potential therapeutic applications particularly in cancer: the water-soluble cytotoxic agents encapsulated in these particles can be targeted to tumors while minimizing the likelihood of toxicity to reticuloendothelial system (RES).
Research Interests: Hydrogels, Adsorption, Pharmaceutics, Dosage Form, In Vitro, and 14 moreKidney, Mice, Animals, Male, Anticoagulants, Encapsulation, In Vivo, Hydrophobicity, Particle Size, Drug Targeting, Reticuloendothelial System, Mononuclear Phagocyte System, fluorescent dyes, and Pharmacology and pharmaceutical sciences
The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific... more
The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific target site is crucial for providing efficient delivery of therapeutics and imaging agents. In this regard, the present study investigates the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles, functionalized with a targeting ligand (EpCAM aptamer) and an imaging agent (quantum dots) for cancer therapy and bioimaging. A wide spectrum of in vitro analysis (cellular uptake study, cytotoxicity assay, cell cycle and apoptosis analysis, apoptosis associated proteins study) revealed superior therapeutic potentiality of targeted drug loaded NPs over other formulations in EpCAM expressing cells. Moreover, our nanotheranostic system served as a superlative bio-imaging modality both in 2D monolayer culture and tumor spheroid...
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High expression of the inducible isoform of heme oxygenase (HO-1) is now well known in solid tumors in humans and experimental animal models. We reported previously that HO-1 may be involved in tumor growth (Tanaka et al., Br. J. Cancer,... more
High expression of the inducible isoform of heme oxygenase (HO-1) is now well known in solid tumors in humans and experimental animal models. We reported previously that HO-1 may be involved in tumor growth (Tanaka et al., Br. J. Cancer, 88: 902-909, 2003), in that inhibition of HO activity in tumors by using zinc protoporphyrin (ZnPP) significantly reduced tumor growth in a rat model. We demonstrate here that poly(ethylene glycol)-conjugated ZnPP (PEG-ZnPP), a water-soluble derivative of ZnPP, exhibited potent HO inhibitory activity and had an antitumor effect in vivo. In vitro studies with cultured SW480 cells, which express HO-1, showed that PEG-ZnPP induced oxidative stress, and consequently apoptotic death, of these cells. Pharmacokinetic analysis revealed that PEG-ZnPP-administered i.v. had a circulation time in blood that was 40 times longer than that for nonpegylated ZnPP. More important, PEG-ZnPP preferentially accumulated in solid tumor tissue in a murine model. In vivo tr...
Research Interests: Cancer, Membrane Proteins, Enzyme Inhibitors, Apoptosis, Humans, and 15 moreMice, Animals, Male, Animal Model, Heme Oxygenase, Poly Ethylene Glycol, Side Effect, Rat Model, In Vitro Studies, Antitumor Activity, Murine Model, Tumor Growth, Antineoplastic Agents, Polyethylene Glycols, and Colonic Neoplasms
Doxycycline is a tetracycline antibiotic with a potent antibacterial activity against a wide variety of bacteria. However, poor cellular penetration limits its use for the treatment of infectious disease caused by intracellular pathogens.... more
Doxycycline is a tetracycline antibiotic with a potent antibacterial activity against a wide variety of bacteria. However, poor cellular penetration limits its use for the treatment of infectious disease caused by intracellular pathogens. One potential strategy to overcome this problem is the use of nanotechnology that can help to easily target the intracellular sites of infection. The antibacterial activity of these antibiotics is enhanced by encapsulating it in polymeric nanoparticles. In this study, we describe the improvement of the entrapment efficiency of doxycycline hydrochloride (doxycycline)-loaded PLGA:PCL nanoparticles up to 70% with variation of different formulation parameters such as polymer ratio, amount of drug loading (w/w), solvent selection, electrolyte addition, and pH alteration in the formulation. We have evaluated the efficacy of these nanoparticles over native doxycycline against a strain of Escherichia coli (DH5α) through growth inhibition and colony counting. The results indicate that doxycycline-loaded nanoparticles have superior effectiveness compared to native doxycycline against the above bacterial strain, resulting from the sustained release of doxycycline from nanoparticles. These results are encouraging for the use of these doxycycline-loaded nanoparticles for the treatment of infections caused by doxycycline-sensitive bacteria.
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Drug delivery is an interdisciplinary and independent field of research and is gaining the attention of pharmaceutical researchers, medical doctors and industry. A safe and targeted drug delivery could improve the performance of some... more
Drug delivery is an interdisciplinary and independent field of research and is gaining the attention of pharmaceutical researchers, medical doctors and industry. A safe and targeted drug delivery could improve the performance of some classic medicines already on the market, and moreover, will have implications for the development and success of new therapeutic strategies such as anticancer drug delivery, peptide and protein delivery and gene therapy. In the last decade, several drug-delivery technologies have emerged and a fascinating part of this field is the development of nanoscale drug delivery devices. Nanoparticles (NPs) have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently, nucleotides. NPs and other colloidal drug-delivery systems modify the kinetics, body distribution and drug release of an associated drug. This review article focuses on the potential of nanotechnology in medicine and discusses different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging. This comprehensive review focuses on different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging.
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Aim: To develop a suitable formulation of curcumin-encapsulated methoxy poly(ethylene glycol) (MePEG)/poly-ε-caprolactone (PCL) diblock copolymeric micelle by varying the copolymer ratio, for achieving small sized micelles with high... more
Aim: To develop a suitable formulation of curcumin-encapsulated methoxy poly(ethylene glycol) (MePEG)/poly-ε-caprolactone (PCL) diblock copolymeric micelle by varying the copolymer ratio, for achieving small sized micelles with high encapsulation of curcumin. To evaluate the micelle’s aqueous solubility and stability, efficiency of cellular uptake, cell cytotoxicity and ability to induce apoptosis on pancreatic cell lines. Method: Amphiphilic diblock copolymers (composed of MePEG and PCL) were used in various ratios for the preparation of curcumin-encapsulated micelles using a modified dialysis method. Physicochemical characterization of the formulation included size and surface charge measurement, transmission electron microscopy characterization, spectroscopic analysis, stability and in vitro release kinetics studies. The anticancer efficacy of the curcumin-encapsulated micelle formulation was compared with unmodified curcumin in terms of cellular uptake, cell cytotoxicity and apo...
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In the development of controlled-release protein therapeutics, the high encapsulation of proteins into biodegradable nanoparticles with uniform size in an anhydrous process along with an excellent redispersion is of practical interest.... more
In the development of controlled-release protein therapeutics, the high encapsulation of proteins into biodegradable nanoparticles with uniform size in an anhydrous process along with an excellent redispersion is of practical interest. The objective of this work was to study the physicochemical and in vitro release properties of chitosan nanoparticles with different molecular weights (low, medium and high) using bovine serum albumin (BSA) as a model protein for developing nanoparticle formulations that were stable and reproducible after lyophilization. The BSA-loaded chitosan nanoparticles were prepared by an ionic gelation method using pentasodium tripolyphosphate as the polyanions. The physicochemical properties and in vitro release kinetics of the nanoparticles were evaluated along with Fourier transform infrared spectroscopy studies. Furthermore, the nanoparticles were freeze-dried for long-term stability in the formulation. To optimize the size of the freeze-dried nanoparticles after redispersion, various types of lyoprotectants (natural and synthetic) were tested in varying concentration in the process of lyophilization. The dynamic light scattering measurements revealed the increase in size of chitosan nanoparticles with the increase in molecular weight of chitosan with no significant change, irrespective of the concentration of BSA entrapped. In addition, the entrapment efficiency of the nanoparticles increased with the increasing molecular weight of chitosan and BSA concentration. By contrast, the redispersity of the freeze-dried samples resulted in further increase of the mean diameter of the nanoparticles. Among the various types of lyoprotectants (natural and synthetic) examined, sucrose proved to be very effective in reducing the size of freeze-dried nanoparticles on redispersion without significant change in surface charge of nanoparticles. Finally, the in vitro release kinetics of BSA from nanoparticles of different molecular weights of chitosan, with and without sucrose, was evaluated and found to depend upon the molecular weight of chitosan.
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Aim: To increase the entrapment efficiency of doxycycline (DXY)-loaded poly(D,L-lactide-co-glycolide) (PLGA):poly(ε-caprolactone) (PCL) nanoparticles by up to 70% by varying the different formulation parameters such as polymer ratio,... more
Aim: To increase the entrapment efficiency of doxycycline (DXY)-loaded poly(D,L-lactide-co-glycolide) (PLGA):poly(ε-caprolactone) (PCL) nanoparticles by up to 70% by varying the different formulation parameters such as polymer ratio, amount of drug loading (w/w), solvent selection, electrolyte addition and pH in the formulation. Method: Biodegradable polymers PLGA and PCL are used in various ratios for nanoparticle preparation using the water-in-oil-in-water double emulsion technique for water-soluble DXY. The physicochemical characterization of nanoparticles included size and surface charge measurement, study of surface morphology using scanning-electron microscopy, Fourier transform infrared spectroscopy study, differential scanning calorimetry analysis and in vitro release kinetics study. Results: The mean particle size ranged from 230 to 360 nm, as measured by dynamic laser light scattering, and scanning-electron microscopy confirmed the spherical nature and smooth surface of th...
Research Interests: Scanning Electron Microscopy, Nanomedicine, Nanoparticles, Nanotechnology, Differential scanning calorimetry, and 10 moreEscherichia coli, Medical Biotechnology, High Pressure Liquid Chromatography, Antibacterial activity, Anti-Bacterial Agents, Particle Size, Fourier transform infrared spectroscopy, Doxycycline, Microbial Sensitivity Tests, and Polyesters
Aim: The objective of the present study is to prepare and characterize nutlin-3a loaded polymeric poly(lactide-co-glycolide) nanoparticles (NPs) surface functionalized with transferrin ligand, to deliver the encapsulated drug in a... more
Aim: The objective of the present study is to prepare and characterize nutlin-3a loaded polymeric poly(lactide-co-glycolide) nanoparticles (NPs) surface functionalized with transferrin ligand, to deliver the encapsulated drug in a targeted manner to its site of action and to evaluate the efficacy of the nanoformulation in terms of its cellular uptake, cell cytotoxicity, cell cycle arrest, apoptosis and activation of p53 pathway at molecular level in MCF-7 breast cancer cell line. Method: Nutlin-3a loaded poly(lactide-co-glycolide) NPs were prepared following the single oil-in-water emulsion method. Physicochemical characterization of the formulation included size and surface charge measurement, transmission electron microscopy characterization, study of surface morphology using scanning electron microscopy, Fourier-transform infrared spectral analysis and in vitro release kinetics studies. Furthermore, targeting ability of the conjugated system was assessed by cellular uptake and ce...
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Research Interests: Scanning Transmission Electron Microscopy, Nanotechnology, Humans, Magnetic nanoparticles, Female, and 15 moreMale, Iron Oxide, Drug Delivery Systems, Doxorubicin, Magnetics, Fourier transform infrared spectroscopy, Sustained Drug Release, Magnetic Nanoparticles, Microspheres, Drug Carriers, Ferric Compounds, Molecular Pharmaceutics, Breast Neoplasms, Prostatic neoplasms, and Pharmacology and pharmaceutical sciences
We studied the molecular mechanism of greater efficacy of paclitaxel-loaded nanoparticles (Tx-NPs) following conjugation to transferrin (Tf) ligand in breast cancer cell line. NPs were formulated using biodegradable polymer,... more
We studied the molecular mechanism of greater efficacy of paclitaxel-loaded nanoparticles (Tx-NPs) following conjugation to transferrin (Tf) ligand in breast cancer cell line. NPs were formulated using biodegradable polymer, poly(lactic-co-glycolide) (PLGA), with encapsulated Tx and conjugated to Tf ligand via an epoxy linker. Tf-conjugated NPs demonstrated greater and sustained antiproliferative activity of the drug in dose- and time-dependent studies compared to that with drug in solution or unconjugated NPs in MCF-7 and MCF-7/Adr cells. The mechanism of greater antiproliferative activity of the drug with conjugated NPs was determined to be due to their greater cellular uptake and reduced exocytosis compared to that of unconjugated NPs, thus leading to higher and sustained intracellular drug levels. The increase in antiproliferative activity of the drug with incubation time in MCF-7/Adr cells with Tf-conjugated NPs suggests that the drug resistance can be overcome by sustaining intracellular drug retention. The intracellular disposition characteristics of Tf-conjugated NPs following their cellular uptake via Tf receptors could have been different from that of unconjugated NPs via nonspecific endocytic pathway, thus influencing the NP uptake, their intracellular retention, and hence the therapeutic efficacy of the encapsulated drug.
Research Interests: Transmission Electron Microscopy, Magnetic Resonance Spectroscopy, Molecular Mechanics, Humans, Cancer Therapy, and 12 moreDrug Resistance, Nanostructures, Transferrin, Temperature, Biodegradable Polymer, Time Dependent, Cell Proliferation, Intracellular Space, Molecular Structure, Breast Cancer Cells, Molecular Pharmaceutics, and Pharmacology and pharmaceutical sciences
Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic used to treat a variety of cancers including leukemia. Chronic myeloid leukemia (CML) blasts like K562 cells are resistant to apoptosis induced by DOX due to several reasons,... more
Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic used to treat a variety of cancers including leukemia. Chronic myeloid leukemia (CML) blasts like K562 cells are resistant to apoptosis induced by DOX due to several reasons, the primary being the sequestration of drug into cytoplasmic vesicles and induction of multidrug resistance (MDR) gene expression with DOX treatment resulting in intracellular resistance to this drug. Moreover, expression of antiapoptotic protein BCL-2 and the hybrid gene bcr/abl in K562 cells contributes resistance to DOX. Studies have shown that curcumin (CUR) has a pleiotropic therapeutic effect in cancer treatment, as it is an inhibitor of nuclear factor kappa B (NFκB) as well as a potent downregulator of MDR transporters. In this study, we investigated the potential benefit of using DOX and CUR in a single nanoparticle (NP) formulation to inhibit the development of drug resistance for the enhancement of antiproliferative activity of DOX in K562 cells. Results illustrate that the dual (DOX+CUR) drug loaded NPs were effectively delivered into K562 cells. CUR not only facilitates the retention of DOX in nucleus for a longer period of time but also inhibits the gradual expression of MDR1 and BCL-2 at the mRNA level in K562 cells. Moreover, Western blot results confirm that in combination both of the drugs were capable of inducing apoptosis even if in a lower concentration compared to either single drug in both solution or in formulation. Combinational therapy by using DOX and CUR, especially when administered in the NP formulation, has enhanced the cytotoxicity in K562 cells by promoting the apoptotic response. Overall, this combinational strategy has significant promise in the clinical management of intractable diseases, especially leukemia.
Research Interests: Flow Cytometry, Cell Cycle, Nanoparticles, Transmission Electron Microscopy, Atomic Force Microscopy, and 11 moreWestern blotting, Humans, P-glycoprotein, Doxorubicin, Fourier transform infrared spectroscopy, Lactic Acid, Cell Survival, Antineoplastic Agents, Molecular Pharmaceutics, reverse transcriptase polymerase chain reaction, and Pharmacology and pharmaceutical sciences
Wound healing is an intricate multistage process that includes inflammation, cell proliferation, matrix deposition and remodeling phases. It is often associated with oxidative stress and consequent prolonged inflammation, resulting in... more
Wound healing is an intricate multistage process that includes inflammation, cell proliferation, matrix deposition and remodeling phases. It is often associated with oxidative stress and consequent prolonged inflammation, resulting in impaired wound healing. Curcumin has been reported to improve wound healing in different animal models. In order to increase the efficacy of curcumin in the healing arena a curcumin loaded oleic acid based polymeric (COP) bandage was formulated. The in vivo wound healing potency was compared with void bandage and control (cotton gauze treatment) in a rat model. Biochemical parameters and histological analysis revealed increased wound reduction and enhanced cell proliferation in COP bandage treated groups due to its efficient free radical scavenging properties. Comparative acceleration in wound healing was due to early implementation of fibroblasts and its differentiation (increased level of α-smooth muscle actin). Western blotting and semiquantitative PCR analysis clearly indicate that COP bandage can efficiently quench free radicals leading to reduced antioxidative enzyme activity. Further evidence at mRNA and protein level indicates that our system is potent enough to reduce the inflammatory response mediated by the NFκB pathway during wound healing. With this background, we anticipate that such a versatile approach may seed new arena for topical wound healing in the near future.
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Cancer is an ever-increasing menace that needs to be curbed soon. Though chemotherapy is successful to some extent, the main drawbacks of chemotherapy is the limited accessibility of drugs to the tumor tissues requiring high doses, their... more
Cancer is an ever-increasing menace that needs to be curbed soon. Though chemotherapy is successful to some extent, the main drawbacks of chemotherapy is the limited accessibility of drugs to the tumor tissues requiring high doses, their intolerable toxicity, development of multiple drug resistance and their non-specific targeting. Nanoparticles (NPs), an evolution of nanotechnology, have the potential to successfully address these problems related to drug delivery and retention and are considered potential candidates to carry drugs to the desired site of therapeutic action. In this review, we give an overview of the use of clinically applicable NPs mainly for cancer therapy. We also focus on the different types of nanoscale polymer carriers used for the delivery of chemotherapeutic agents and the mechanisms that facilitate their targeted delivery to tumor cells.
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Polyvinyl alcohol (PVA) is the most commonly used emulsifier in the formulation of poly lactide and poly (D,L-lactide-co-glycolide) (PLGA) polymeric nanoparticles. A fraction of PVA remains associated with the nanoparticles despite... more
Polyvinyl alcohol (PVA) is the most commonly used emulsifier in the formulation of poly lactide and poly (D,L-lactide-co-glycolide) (PLGA) polymeric nanoparticles. A fraction of PVA remains associated with the nanoparticles despite repeated washing because PVA forms an interconnected network with the polymer at the interface. The objective of this study was to determine the parameters that influence the amount of residual PVA associated with PLGA nanoparticles and its effect on the physical properties and cellular uptake of nanoparticles. Nanoparticles were formulated by a multiple emulsion-solvent evaporation technique using bovine serum albumin (BSA) as a model protein. The parameters that affected the amount of residual PVA include the concentration of PVA and the type of organic solvent used in the emulsion. The residual PVA, in turn, influenced different pharmaceutical properties of nanoparticles such as particle size, zeta potential, polydispersity index, surface hydrophobicity, protein loading and also slightly influenced the in vitro release of the encapsulated protein. Importantly, nanoparticles with higher amount of residual PVA had relatively lower cellular uptake despite their smaller particle size. It is proposed that the lower intracellular uptake of nanoparticles with higher amount of residual PVA could be related to the higher hydrophilicity of the nanoparticle surface. In conclusion, the residual PVA associated with nanoparticles is an important formulation parameter that can be used to modulate the pharmaceutical properties of PLGA nanoparticles.
Research Interests: Biomedical Engineering, Nanotechnology, Polymers, Humans, Controlled release, and 15 moreHydrophobicity, Phagocytosis, Polyvinyl alcohol, Particle Size, Sustained Drug Release, Surface Properties, Indexation, Bovine Serum Albumin, Zeta Potential, Biocompatible Materials, Drug Carriers, Lactic Acid, Excipients, Physical Properties, and Pharmacology and pharmaceutical sciences
The objective of the study was to investigate the effect of particle size of nano- and microparticles formulated from poly(D,L-lactide-co-glycolide) (50:50 PLGA) on polymer degradation and protein release. Since the surface area to volume... more
The objective of the study was to investigate the effect of particle size of nano- and microparticles formulated from poly(D,L-lactide-co-glycolide) (50:50 PLGA) on polymer degradation and protein release. Since the surface area to volume ratio is inversely proportional to the particle size, it is hypothesized that the particle size would influence the polymer degradation as well as the release of the encapsulated protein. PLGA nano- and microparticles of approximate mean diameters of 0.1, 1 and 10 microm, containing bovine serum albumin as a model protein, were formulated using a multiple water-in-oil-in-water emulsion solvent evaporation technique. These particles were incubated at 37 degrees C in phosphate-buffered saline (pH 7.4, 154 mM) and the particles were characterized at various time points for molecular weight of polymer, surface-associated polyvinyl alcohol content (PVA), and the particle surface topology using scanning electron microscopy. The supernatants from the above study were analyzed for the released protein and PVA content. Polymer degradation was found to be biphasic in both nano- and microparticles, with an initial rapid degradation for 20-30 days followed by a slower degradation phase. The 0.1 microm diameter nanoparticles demonstrated relatively higher polymer degradation rate (P<0.05) during the initial phase as compared to the larger size microparticles (first order degradation rate constants of 0.028 day(-1), 0.011 day(-1) and 0.018 day(-1) for 0.1, 1 and 10 microm particles, respectively), however the degradation rates were almost similar (0.008 to 0.009 day(-1)) for all size particles during the later phase. All size particles maintained their structural integrity during the initial degradation phase; however, this was followed by pore formation, deformation and fusion of particles during the slow degradation phase. Protein release from 0.1 and 1 microm particles was greater than that from 10 microm size particles. In conclusion, the polymer degradation rates in vitro were not substantially different for different size particles despite a 10- and 100-fold greater surface area to volume ratio for 0.1 microm size nanoparticles as compared to 1 and 10 microm size microparticles, respectively. Relatively higher amounts of the surface-associated PVA found in the smaller-size nanoparticles (0.1 microm) as compared to the larger-size microparticles could explain some of the observed degradation results with different size particles.
Research Interests: Biomedical Engineering, Nanoparticle, Drug delivery, Nanotechnology, Dosage Form, and 15 moreBiodegradation, In Vitro, Controlled release, Animals, Biodegradable Polymers, Cattle, Encapsulation, Biodegradable Polymer, Particle Size, First Order Logic, Molecular weight, Microspheres, Bovine Serum Albumin, Active Ingredient, and Lactic Acid
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Chemotherapy remains the preferred choice of treatment for prostate cancer but modest drug response and significant toxicity by conventional methods of administration limit their efficacy. In our study, we determined the efficacy of... more
Chemotherapy remains the preferred choice of treatment for prostate cancer but modest drug response and significant toxicity by conventional methods of administration limit their efficacy. In our study, we determined the efficacy of paclitaxel (Tx)-loaded biodegradable nanoparticles (NPs) on tumor inhibition. We hypothesized that NPs following conjugation to transferrin (Tf) ligand (NPs-Tf) would enhance the therapeutic efficacy of the encapsulated drug. The antiproliferative activity of NPs was determined in human prostate cancer cell line (PC3) and their effect on tumor inhibition in a murine model of prostate cancer. NPs (approximately 220 nm in diameter, 5.4% w/w drug loading) under in vitro conditions exhibited sustained release of the encapsulated drug (60% release in 60 days). The IC50 (concentration of drug for 50% inhibition of cell growth) of the drug with Tf-conjugated NPs (Tx-NPs-Tf) was about 5-fold lower than that with unconjugated NPs (Tx-NPs) or drug in solution. Animals that received a single-dose intratumoral injection of Tx-NPs-Tf (Tx dose= 4 mg/kg) demonstrated complete tumor regression and greater survival rate than those that received either Tx-NPs or Tx-Cremophor EL formulation. In conclusion, sustained release NPs demonstrated greater antitumor activity following their conjugation to Tf ligand.