The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed... more
The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shap...
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Biomolecules can be oxidized by free radicals. This oxidative damage has an important etiological role in aging and the development of diseases like cancer, atherosclerosis, and other inflammatory disorders. Synthetic antioxidants, such... more
Biomolecules can be oxidized by free radicals. This oxidative damage has an important etiological role in aging and the development of diseases like cancer, atherosclerosis, and other inflammatory disorders. Synthetic antioxidants, such as butylated hydroxyl anisole, are good free radical scavengers; however, they can be carcinogenic. Therefore, there is an increasing interest in searching for antioxidants of natural origin. Acacia nilotica has a versatile medicinal value as folk medicine. The present study aims at screening the methanol and aqueous extracts of the pods of Acacia nilotica for antioxidant activity. The effect of these extracts on inhibition of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide radicals and of lipid peroxidation was studied. The results indicated that both the extracts exhibited a significant reduction in the DPPH and NO radical production along with a significant reduction in lipid peroxidation. The results indicate the pods of Acacia nilotica to be...
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Polyethylene glycol-ylation (PEGylation) is a phenomenon of modification of a protein, peptide, or non-peptide molecule by linking of one or more polyethylene glycol chains. These synthetic polymers have received FDA approval for internal... more
Polyethylene glycol-ylation (PEGylation) is a phenomenon of modification of a protein, peptide, or non-peptide molecule by linking of one or more polyethylene glycol chains. These synthetic polymers have received FDA approval for internal use. It is an effective method of delivering therapeutic proteins as it modifies their pharmacokinetic properties. The PEG-drug conjugates have several advantages - prolonged residence in body, decreased degradation by metabolic enzymes and reduction or elimination of protein immunogenicity. The delivery of several classes of protein drugs (including protein scaffolds, enzymes, cytokines and antibodies) is significantly improved by PEG-drug conjugate and they are useful in treating chronic diseases such as hepatitis C, leukemia, acromegaly, severe combined immunodeficiency disease (SCID), chronic gout, rheumatoid arthritis, and Crohn’s disease. This review envisages an overview of PEGylation and its applications in cancer therapeutics. PEGylation t...
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The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring... more
The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecule...
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Polyherbal formulations have proved to be efficacious for the therapeutic treatment of various diseases, However, the development of validated robust analytical methods for quantification is a major challenge. The aim of this project was... more
Polyherbal formulations have proved to be efficacious for the therapeutic treatment of various diseases, However, the development of validated robust analytical methods for quantification is a major challenge. The aim of this project was to develop a simple analytical method for the quantification of 6-gingerol (6-GIN), E-guggulsterone (E-GGS) and Z-guggulsterone (Z-GGS) in nanoemulsion based gel using reverse phase high performance liquid chromatography (RP-HPLC). 6-GIN, E-GGS and Z-GGS were quantified using acetonitrile: water: methanol (70:20:10 V/V/V) as the mobile phase at 1.0 mL min-1 flow rate with photodiode array detection. The developed method was validated for linearity, accuracy, precision, specificity and robustness as per ICH Q2 (R1) guidelines. The drug content of the three actives in the developed nanoemulgel was found to be between 90% to 110% w/w. The developed analytical method is simple and can be used for quantification of 6-GIN, E-GGS and Z-GGS in fixed dose pr...
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Alzheimer’s disease is a complex, progressive, neurodegenerative disorder with a multifactorial etiology. More than one mechanism appears to be involved in its pathogenesis. Current treatment targeting only a single mechanism provides... more
Alzheimer’s disease is a complex, progressive, neurodegenerative disorder with a multifactorial etiology. More than one mechanism appears to be involved in its pathogenesis. Current treatment targeting only a single mechanism provides only symptomatic relief and is unable to stop the progression of the disease. There is a substantial unmet medical need to develop more efficacious drugs that can address all the causative factors that lead to the development and progression of Alzheimer’s disease. One of the strategies which has emerged is the development of chimeric conjugate compounds, in which multiple bioactive components are combined to form novel molecular entities, that can simultaneously regulate multiple mechanisms effectively. This chapter presents an overview of the various factors contributing to the pathophysiology of Alzheimer’s disease. Chimeric strategies that are being developed to supplement the single-mechanism targeting acetylcholinesterase drugs, which are current...
Abstract The clinical therapeutic regimen for disease treatment of the anterior portion of an eye involves the use of eye drops with mediocre success due to rapid eye drainage and poor bioavailability. These conventional delivery... more
Abstract The clinical therapeutic regimen for disease treatment of the anterior portion of an eye involves the use of eye drops with mediocre success due to rapid eye drainage and poor bioavailability. These conventional delivery mechanisms do not penetrate the posterior portion of the eye and are ineffective in treating posterior segment diseases like, retinitis pigmentosa, age related macular degeneration, diabetic retinopathies, and glaucoma. This has led to augmented research in development of drug delivery alternatives for subconjunctival and periocular administration, drug that targets bloodstream to the retinal pigment epithelium or choroidal vasculature, and prodrugs. Ocular pharmacokinetics is a highly studied area to develop strategies that circumvent the associated barriers in ocular drug delivery and achieve better clinical outcomes. The viable strategies for enhancing ocular bioavailability involves physical methods like formulating drugs as solutions, suspensions, gels and chemical methods like development of prodrugs and soft drugs. The application of prodrug design offers the advantages of higher ocular tissue permeability, superior bioavailability, transporter targeting, site specificity and enhanced aqueous solubility with minimal disruption of the barriers to ocular diffusion. This review focuses mainly on recent progress in prodrug strategies like lipid-based prodrugs, transporter targeted prodrugs, hydrophilic and polymeric prodrugs developed to improve delivery to the otherwise resilient eye. The success of conventional and emerging prodrug design strategies depends on many factors like chemical structure of the drug, ease of prodrug synthesis, capacity of targeted transporters and in vivo metabolic activation attributes. Inspite of the associated challenges, prodrugs have witnessed reasonable market success and the new prodrug design strategies are envisaged to enable delivery of conventional drugs, antibodies, oligonucleotides, genes, and growth factors to the eye offering patient compliant, safer and superior treatment of posterior segment diseases.
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ABSTRACT The Indian Banyan is a large tree, bearing many aerial roots. An aqueous decoction of the fresh aerial roots of this tree has been used by traditional Ayurvedic medical practitioners to boost the immune system in various... more
ABSTRACT The Indian Banyan is a large tree, bearing many aerial roots. An aqueous decoction of the fresh aerial roots of this tree has been used by traditional Ayurvedic medical practitioners to boost the immune system in various diseases. In AIDS, death occurs eventually due to the failing immune system hence new therapies directed towards augmenting the functional capacity of the immune system are the need of the hour. Studies carried out in our laboratory have indicated the immunostimulant activity of the methanol and aqueous extracts of the aerial roots. The aqueous extract was found to enhance the cell mediated and antibody mediated immune responses in rats. The aqueous extract was subjected to fractionation using solvents of varying polarity. This process generated four fractions namely chloroform fraction, ethyl acetate fraction, n-butanol fraction and the aqueous fraction. These fractions were screened for immunomodulatory activity using the in vitro lymphocyte proliferation assay in an effort to identify the most bioactive fraction. The results of this assay indicated that the aqueous fraction exhibited maximum immunostimulatory activity (80% stimulation of lymphocytes at 1 µg/ml) while the other three fractions did not exhibit stimulation of lymphocytes at the concentrations tested (0.001- 10 µg/ml). Hence the aqueous fraction was taken up for evaluation of in vivo immunomodulatory activity. The aqueous fraction was evaluated at doses ranging from 25 mg/kg to 200 mg/kg body weight in rats using the hypersensitivity reaction assay and the hemagglutination reaction assay. The maximum response was observed at 50 mg/kg. The aqueous fraction of the aqueous extract exhibited significant stimulation of cell mediated and antibody mediated immunity and could prove beneficial in diseases involving suppression of the immune system like AIDS.
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In today's world of modern medicine and novel therapies, cancer still remains to be one of the prime contributor to the death of people worldwide. The modern therapies improve condition of cancer patients and are effective in early... more
In today's world of modern medicine and novel therapies, cancer still remains to be one of the prime contributor to the death of people worldwide. The modern therapies improve condition of cancer patients and are effective in early stages of cancer but the advanced metastasized stage of cancer remains untreatable. Also most of the cancer therapies are expensive and are associated with adverse side effects. Thus, considering the current status of cancer treatment there is scope to search for efficient therapies which are cost-effective and are associated with lesser and milder side effects. Phytochemicals have been utilized for many decades to prevent and cure various ailments and current evidences indicate use of phytochemicals as an effective treatment for cancer. Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling cascades is a common phenomenon in most types of cancers. Thus, natural substances targeting PI3K pathway can be of great therapeutic potential in the trea...
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Natural resources continue to be an invaluable source of new, novel chemical entities of therapeutic utility due to the vast structural diversity observed in them. The quest for new and better drugs has witnessed an upsurge in exploring... more
Natural resources continue to be an invaluable source of new, novel chemical entities of therapeutic utility due to the vast structural diversity observed in them. The quest for new and better drugs has witnessed an upsurge in exploring and harnessing nature especially for discovery of antimicrobial, antidiabetic, and anticancer agents. Nature has historically provide us with potent anticancer agents which include vinca alkaloids [vincristine (VCR), vinblastine, vindesine, vinorelbine], taxanes [paclitaxel (PTX), docetaxel], podophyllotoxin and its derivatives [etoposide (ETP), teniposide], camptothecin (CPT) and its derivatives (topotecan, irinotecan), anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin), and others. In fact, half of all the anti-cancer drugs approved internationally are either natural products or their derivatives and were developed on the basis of knowledge gained from small molecules or macromolecules that exist in nature. Three new anti-cancer dru...
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A biofilm is a community of stable microorganisms encapsulated in an extracellular matrix produced by themselves. Many types of microorganisms that are found on living hosts or in the environment can form biofilms. These include... more
A biofilm is a community of stable microorganisms encapsulated in an extracellular matrix produced by themselves. Many types of microorganisms that are found on living hosts or in the environment can form biofilms. These include pathogenic bacteria that can serve as a reservoir for persistent infections, and are culpable for leading to a broad spectrum of chronic illnesses and emergence of antibiotic resistance making them difficult to be treated. The absence of biofilm-targeting antibiotics in the drug discovery pipeline indicates an unmet opportunity for designing new biofilm inhibitors as antimicrobial agents using various strategies and targeting distinct stages of biofilm formation. The strategies available to control biofilm formation include targeting the enzymes and proteins specific to the microorganism and those involved in the adhesion pathways leading to formation of resistant biofilms. This review primarily focuses on the recent strategies and advances responsible for i...
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Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of... more
Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutic...
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Objective: The present study aims to standardize four marketed brands of Balarishta, an Ayurvedic formulation viz. Baidyanath-Balarishta (BB), Dabur-Balarishta (DB), Zandu-Balarishta (ZB) and Nagarjuna-Balarishta (NB) with respect to... more
Objective: The present study aims to standardize four marketed brands of Balarishta, an Ayurvedic formulation viz. Baidyanath-Balarishta (BB), Dabur-Balarishta (DB), Zandu-Balarishta (ZB) and Nagarjuna-Balarishta (NB) with respect to their physicochemical (organoleptic properties, pH, specific gravity, total solid content, ethanol content, reducing and non-reducing sugar content), phytochemical and microbial parameters (total bacterial count, total fungal count and test for specific pathogens viz. P. aeruginosa, E. coli and S. aureus). It also aims to develop and validate a new highperformance thin layer chromatography (HPTLC) method for simultaneous determination of three major phytoconstituents present in Balarishta viz. withaferin A, gallic acid and ephedrine. Methods: ‘Protocol for testing Ayurveda, Siddha and Unani medicines’ was used as a reference for conducting standardization experiments. HPTLC method was developed on Camag Linomat-5 using silica gel 60 GF 254 Results: The ...
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Gemcitabine hydrochloride niosomes were developed in our laboratory in an effort to improve the efficacy of the drug via development of nanotechnology based delivery system. As a part of this exercise, an analytical method was developed... more
Gemcitabine hydrochloride niosomes were developed in our laboratory in an effort to improve the efficacy of the drug via development of nanotechnology based delivery system. As a part of this exercise, an analytical method was developed and validated to evaluate the developed formulation for assay and release profile studies. A simple, precise, specific and rapid high performance liquid chromatographic method was developed for determination of gemcitabine hydrochloride in niosomes. The developed method exhibited good resolution, short run time and low cost of analysis. The chromatographic analysis was carried on a Waters® (C18, 250 mm x4.6 mm, 5µ) column using water: acetonitrile (95:5 v/v) as the mobile phase, flow rate of 1.2 ml/min and detection at 268 nm. The robustness of the method was evaluated using design of experiments. The validation studies of the developed method were conducted as per ICH guidelines Q2 (R1). The results indicated that the developed method as specific, a...
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Background: A novel series of 2-(Morpholin-4-yl)-N-phenylquinazolin-4- amine derivatives were synthesized and confirmed with spectral and elemental techniques. Methods: The compounds were tested for analgesic and anti-inflammatory... more
Background: A novel series of 2-(Morpholin-4-yl)-N-phenylquinazolin-4- amine derivatives were synthesized and confirmed with spectral and elemental techniques. Methods: The compounds were tested for analgesic and anti-inflammatory activity by various pain models in rodents whereas the selectivity towards COX-2 receptor is determined by in vitro assay. Results: Screening results of compounds exhibited comparable biological activity with that of standard compound Indomethacin used for study. Compound 5d was found to be significantly potent with respect to its anti-inflammatory and analgesic activity with substantial COX-II selectivity. Conclusion: In silico analysis by molecular docking and 3D-QSAR studies justifies activity profile of compound 5d, suggesting that it may have potential for further evaluation and development as lead molecule for therapy in pain management.
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Candidiasis is a fungal infection caused by yeasts that belong to the genus Candida. There are over twenty species of Candida yeasts that can cause infection in humans, the most common of which is Candida albicans. Candida yeasts normally... more
Candidiasis is a fungal infection caused by yeasts that belong to the genus Candida. There are over twenty species of Candida yeasts that can cause infection in humans, the most common of which is Candida albicans. Candida yeasts normally reside in the intestinal tract and can be found on mucous membranes and skin without causing infection; however, overgrowth of these organisms can cause symptoms to develop. Presence of other diseases that compromises the patient's immunity makes it more difficult to treat. Candidiasis is majorly divided into superficial infections (oral or vaginal) and systemic infections, also known as invasive candidiasis. The conventional therapeutic modalities used to treat candidiasis are associated with several side effects that limits the dose and dosing frequency. Development of novel drug delivery systems for reduction in dose and alleviation of side effects is an important strategy to improve the clinical efficacy and patient acceptability. This revi...
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Tumor is a heterogeneous mass of malignant cells co-existing with non-malignant cells. This co-existence evolves from the initial developmental stages of the tumor and is one of the hallmarks of cancer providing a protumorigenic niche... more
Tumor is a heterogeneous mass of malignant cells co-existing with non-malignant cells. This co-existence evolves from the initial developmental stages of the tumor and is one of the hallmarks of cancer providing a protumorigenic niche known as tumor microenvironment (TME). Proliferation, invasiveness, metastatic potential and maintenance of stemness through cross-talk between tumors and its stroma forms the basis of TME. Areas covered: The article highlights the developmental phases of a tumor from dysplasia to the formation of clinically detectable tumors. The authors discuss the mechanistic stages involved in the formation of TME and its contribution in tumor outgrowth and chemoresistance. The authors have reviewed various approaches for targeting TME and its hallmarks along with their advantages and pitfalls. The authors also highlight cancer stem cells (CSCs) that are resistant to chemotherapeutics and thus a primary reason for tumor recurrence thereby, posing a challenge for th...
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ABSTRACT A comparative study was undertaken on dissolution studies of marketed formulations which contain Tamsulosin HCl (TAM) and Tolterodine Tartrate (TOL) in a combination of 0.4 mg and 4.0 mg respectively in an extended release form.... more
ABSTRACT A comparative study was undertaken on dissolution studies of marketed formulations which contain Tamsulosin HCl (TAM) and Tolterodine Tartrate (TOL) in a combination of 0.4 mg and 4.0 mg respectively in an extended release form. The dissolution method developed was then used to study three marketed formulations, quantification being done using a validated HPLC method. Comparison of dissolution data was done using the Moor and Flanner model independent method which included determination of Similarity factor and Difference factor. The kinetics of the dissolution process were determined by analyzing the dissolution data using four kinetic equations; namely zero order, first order, higuchi square root and hixson Cube root equation. The results obtained were within the acceptance criteria. The kinetic study indicated that the dissolution data followed first order kinetics and hixson Crowell cube root equation as straight line were obtained with a slope of approximately one and small value of intercept.
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A comparative study was undertaken on dissolution studies of marketed formulations which contain Tamsulosin HCl (TAM) and Tolterodine Tartrate (TOL) in a combination of 0.4 mg and 4.0 mg respectively in an extended release form. The... more
A comparative study was undertaken on dissolution studies of marketed formulations which contain Tamsulosin HCl (TAM) and Tolterodine Tartrate (TOL) in a combination of 0.4 mg and 4.0 mg respectively in an extended release form. The dissolution method developed was then used to study three marketed formulations, quantification being done using a validated HPLC method. Comparison of dissolution data was done using the Moor and Flanner model independent method which included determination of Similarity factor and Difference factor. The kinetics of the dissolution process were determined by analyzing the dissolution data using four kinetic equations; namely zero order, first order, higuchi square root and hixson Cube root equation. The results obtained were within the acceptance criteria. The kinetic study indicated that the dissolution data followed first order kinetics and hixson Crowell cube root equation as straight line were obtained with a slope of approximately one and small val...