The outbreak of SARS-CoV-2 infection has presented the world with an urgent demand for advanced d... 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.
Pancreatic cancer is considered as one of the most lethal type of cancer with a poor 5-year survi... 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...
Tumors are heterogeneous and contain a small population of cells that has a crucial role in tumor... 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.
Brain diseases are the most serious health problems; represent a significant and worldwide public... 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.
Mesenchymal stem cells (MSCs) have gained much interest to be used as targeting vehicle in cancer... 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.
European Journal of Pharmaceutics and Biopharmaceutics, 2015
Combination therapy in cancer is now opted as a potential therapeutic strategy for cancer treatme... 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.
Nowadays, emerging aspects of cancer therapy involve both diagnostic and therapeutic modules in a... 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.
The intricate problems associated with the delivery and various unnecessary in vivo transitions o... 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...
The outbreak of SARS-CoV-2 infection has presented the world with an urgent demand for advanced d... 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.
Pancreatic cancer is considered as one of the most lethal type of cancer with a poor 5-year survi... 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...
Tumors are heterogeneous and contain a small population of cells that has a crucial role in tumor... 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.
Brain diseases are the most serious health problems; represent a significant and worldwide public... 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.
Mesenchymal stem cells (MSCs) have gained much interest to be used as targeting vehicle in cancer... 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.
European Journal of Pharmaceutics and Biopharmaceutics, 2015
Combination therapy in cancer is now opted as a potential therapeutic strategy for cancer treatme... 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.
Nowadays, emerging aspects of cancer therapy involve both diagnostic and therapeutic modules in a... 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.
The intricate problems associated with the delivery and various unnecessary in vivo transitions o... 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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