Department of Pharmacy
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Item Nanocarriers for topical delivery in psoriasis(Elsevier, 2020) Singhvi, GautamPsoriasis is a chronic autoimmune skin disorder that affects millions of people across the planet. It causes many serious complications to afflicted patients and is indicated by uncontrolled growth and differentiation of keratinocytes. Conventional dosage forms have been used for the topical delivery of antipsoriatic drugs but they possess their own limitations. These include poor patient compliance, inadequate penetration and targeting to diseased skin, and local toxicity. In recent decades nanocarriers like liposomes, micelles, and solid lipid nanoparticles have shown potential in delivering antipsoriatic active compounds to the targeted areas of skin. Such novel formulations improve therapeutic efficacy, increase localization of drug in the skin, and decrease side effects. This chapter sheds light on the current advancements in the field of nanocarriers in treating the psoriatic skin condition.Item Nanocarriers as Potential Targeted Drug Delivery for Cancer Therapy(Springer, 2020-01) Singhvi, GautamCancer is a disease characterized by the uncontrolled growth of cells and is the leading cause of death worldwide with an incidence of 11 million new cases each year. Nanotechnology-based drug delivery systems have received much attention for cancer treatment. Nanocarriers are the delivery systems which are prepared by alteration of the size (1–1000 nm) and shape of a material to the nano-range level. Nanocarriers are prepared by utilizing natural, polymeric, inorganic magnetic silica-based materials. Various nanocarriers including liposomes, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, magnetic nanoparticles, and other inorganic nanoparticles have been investigated for diagnostic, therapeutic, and drug targeting in cancer therapy. Nanocarriers act as a cancer-specific drug delivery or diagnostic agent by inherent passive targeting mechanism or adopted active targeting strategies by altering the surface properties with specific ligands. Targeted nanoparticulate systems increase the accumulation of the chemotherapeutic agent in the tumor tissue and reduce the toxicity to healthy cells. Nanocarriers extend the drug release for a longer duration and protect the drug from degradation. Nanocarriers are also proven effective for improving the pharmacokinetics of poorly soluble hydrophobic drugs by solubilizing or permeating them through lipophilic biological barriers.Item Nanoparticulate Drug Delivery Systems for Brain Targeting(Taylor & Francis, 2021-03) Singhvi, GautamThis new volume, Nanocarriers for Brain Targeting: Principles and Applications, covers recent research on brain physiology and the development of drug delivery systems. It explores a diverse variety of strategies that can be employed to achieve drug targeting to the brain. The nanocarriers that are discussed include nanoparticles, vesicular carriers, carriers having carbon as a core constituent, dispersed systems, and more. The inherent anatomy and physiology of the brain renders it different from other organs. The past few decades have witnessed significant research on brain ailments in response to a majority of hospitalizations that occur due to age-related central nervous system disorders. The prevalence of diverse diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-dementia, etc., affect about 1.5 billion people globally, which is further anticipated to reach 1.9 billion by the year 2020. Nanocarriers for drug delivery to the brain are seen as one of the answers to this growing problem.Item Application of QbD Principles in Nanocarrier-Based Drug Delivery Systems(Elsevier, 2019) Singhvi, GautamDevelopment of nanomedicines has become an attractive strategy in the delivery of therapeutics to overcome the problems associated with conventional therapy especially for cancer, skin infections, tuberculosis, and other long-term disorders. Preparation of nanocarriers includes multiple constituents and multiple steps which need to be understood in-depth. It is expected that the application of quality by design (QbD) approach can overcome the existing issues related to nanoformulation development and can provide wider acceptability for regulatory agencies to form constructive guidelines for their approval. The objective of QbD in nanocarrier drug delivery is to derive meaningful product specifications based on safety, efficacy, and clinical performance. It helps in investigation of variable factors with respect to materials and process involved and ultimately enhances the process capability with minimum product variability. This book chapter has compiled various QbD components which can be easily implemented for preparation and optimization of robust nanoformulations.Item Nanocarriers For Drug Delivery: Mini Review(Bentham Science, 2018) Singhvi, GautamNanocarriers have been a part of drug delivery for some decades now. Due to the enormous advantages offered by them, they are replacing the conventionally available systems.Item Nanocarriers for ocular drug delivery: current status and translational opportunity(RSC, 2020) Singhvi, GautamOcular diseases have a significant effect on vision and quality of life. Drug delivery to ocular tissues is a challenge to formulation scientists. The major barriers to delivering drugs to the anterior and posterior segments include physiological barriers (nasolacrimal drainage, blinking), anatomical barriers (static and dynamic), efflux pumps and metabolic barriers. The static barriers comprise the different layers of the cornea, sclera, and blood–aqueous barriers whereas dynamic barriers involve conjunctival blood flow, lymphatic clearance and tear drainage. The tight junctions of the blood–retinal barrier (BRB) restrict systemically administered drugs from entering the retina. Nanocarriers have been found to be effective at overcoming the issues associated with conventional ophthalmic dosage forms. Various nanocarriers, including nanodispersion systems, nanomicelles, lipidic nanocarriers, polymeric nanoparticles, liposomes, niosomes, and dendrimers, have been investigated for improved permeation and effective targeted drug delivery to various ophthalmic sites. In this review, various nanomedicines and their application for ophthalmic delivery of therapeutics are discussed. Additionally, scale-up and clinical status are also addressed to understand the current scenario for ophthalmic drug delivery.Item Targeted drug-delivery systems in the treatment of rheumatoid arthritis: recent advancement and clinical status(Future Science Group, 2020-05) Singhvi, GautamRheumatoid arthritis (RA) is a chronic systemic autoimmune disease that is characterized by synovial inflammation, cellular infiltration in joints which leads to progressive joint destruction and bone erosion. RA is associated with many comorbidities including pulmonary disease, rheumatoid nodules and can have a pessimistic impact on quality of life. The current therapies of RA treatment comprise conventional, small molecule and biological antirheumatic drugs. Their utility as therapeutic agents is limited because of poor absorption, rapid metabolism and adverse effects (dose-escalation, systemic toxicity, lack of selectivity and safety). To overcome these limitations, the novel drug delivery systems are being investigated. This review has compiled currently approved therapies along with emerging advanced drug-delivery systems for RA treatment. Further, active targeting of therapeutic agents to inflamed joints via folate receptor, CD44, angiogenesis, integrins and other provided an improved therapeutic efficacy in the treatment of RA.Item Curcumin loaded nanostructured lipid carriers for enhanced skin retained topical delivery: optimization, scale-up, in-vitro characterization and assessment of ex-vivo skin deposition(Elsevier, 2020-09) Singhvi, Gautam; Roy, AniruddhaNanostructured lipid carriers (NLC) have become a promising drug delivery system for topical delivery of drugs. Delivery of lipophilic drugs with improved stability and entrapment efficiency is one of the foremost benefits of NLC based formulations. The objective of the present study was to improve the permeation of poorly soluble curcumin into topical skin layers for the treatment of chronic inflammatory disorder psoriasis and microbial mediated acne vulgaris. Hot emulsification followed by probe sonication method was employed for the preparation of the curcumin loaded NLC. Further, in-vitro and ex-vivo characterization was performed for designed NLC. The designed NLC showed a mean particle size 96.2 ± 0.9 nm, entrapment efficiency of 70.5 ± 1.65% and zeta potential of -15.2 ± 0.566 mV. Curcumin-NLC showed extended in-vitro release upto 48 hours, whereas free curcumin showed 100% drug release within 4 hours. Ex-vivo skin permeation studies revealed 3.24 fold improved permeation and skin retention in the case of curcumin loaded NLC gel compared to free curcumin gel. The cell viability studies demonstrated the formulation components showed no toxicity towards keratinocyte cells. In keratinocyte cells, improved cell uptake was observed for curcumin-NLC compared to free curcumin dispersion. The results suggested that the NLC based formulation had potential to improve the efficacy of curcumin.Item Emerging Trends in Topical Delivery of Curcumin Through Lipid Nanocarriers: Effectiveness in Skin Disorders(Springer, 2020) Singhvi, GautamCurcumin is a unique molecule naturally obtained from rhizomes of Curcuma longa. Curcumin has been reported to act on diverse molecular targets like receptors, enzymes, and co-factors; regulate different cellular signaling pathways; and modulate gene expression. It suppresses expression of main inflammatory mediators like interleukins, tumor necrosis factor, and nuclear factor κB which are involved in the regulation of genes causing inflammation in most skin disorders. The topical delivery of curcumin seems to be more advantageous in providing a localized effect in skin diseases. However, its low aqueous solubility, poor skin permeation, and degradation hinder its application for commercial use despite its enormous potential. Lipid-based nanocarrier systems including liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lyotropic liquid crystal nanoparticles, lipospheres, and lipid nanocapsules have found potential as carriers to overcome the issues associated with conventional topical dosage forms. Nano-size, lipophilic nature, viscoelastic properties, and occlusive effect of lipid nanocarriers provide high drug loading, hydration of skin, stability, enhanced permeation through the stratum corneum, and slow release of curcumin in the targeted skin layers. This review particularly focuses on the application of lipid nanocarriers for the topical delivery of curcumin in the treatment of various skin diseases. Furthermore, preclinical studies and patents have also indicated the emerging commercialization potential of curcumin-loaded lipid nanocarriers for effective drug delivery in skin disorders.Item Role of stealth lipids in nanomedicine-based drug carriers(Elsevier, 2021-03) Singhvi, GautamThe domain of nanomedicine owns a wide-ranging variety of lipid-based drug carriers, and novel nanostructured drug carriersthat are further added to this range every year. The primary goal behind the exploration of any new lipid-based nanoformulation is the improvement of the therapeutic index of the concerned drug molecule along with minimization in the associated side-effects. However, for maintaining a sustained delivery of these intravenously injected lipoidal nanomedicines to the targeted tissues and organ systems in the body, longer circulation in the bloodstream, as well as their stability, are important. After administration, upon recognition as foreign entities in the body, these systems are rapidly cleared by the cells associated with the mononuclear phagocyte system. In order to provide these lipid-based systems with long circulation characteristics, techniques such as coating of the lipoidal surface with an inert polymeric material like polyethylene glycol (PEG) assists in imparting ‘stealth properties’ to these nanoformulations for avoiding recognition by the macrophages of the immune system. In this review, detailed importance is given to the hydrophilic PEG polymer and the role played by PEG-linked lipid polymers in the field of nanomedicine-based drug carriers. The typical structure and classification of stealth lipids, clinical utility, assemblage techniques, physicochemical characterization, and factors governing the in-vivo performance of the PEG-linked lipids containing formulations will be discussed. Eventually, the novel concept of accelerated blood clearance (ABC) phenomenon associated with the use of PEGylated therapeutics will be deliberated.