Rahul Maheshwari

Augmented delivery of gemcitabine in lung cancer cells exploring mannose anchored solid lipid nanoparticles

Gemcitabine (GmcH) is an effective anti-cancer agent used in the chemotherapy of lung cancer. However, the clinical applications of GmcH has been impeded primarily due to its low blood residence time, unfavorable pharmacokinetic and pharmacodynamic (PK/PD) profile, and poor penetration in the complex environment of lung cancer cells. Thus, the present study aims to formulate GmcH loaded mannosylated solid lipid nanoparticles (GmcH-SLNs) for improving its drug uptake into the lung cancer cells. GmcH-SLNs were prepared by emulsification and solvent evaporation process, and surface modification was done with mannose using ring opening technique. The cellular toxicity and cell uptake studies were performed in A549 lung adenocarcinoma cell line. The developed nanoformulation appears to be proficient in targeted delivery of GmcH with improved therapeutic effectiveness and enhanced safety.

Nanocarriers Assisted siRNA Gene Therapy for the Management of Cardiovascular Disorders.

Cardiovascular diseases (CVDs), primarily myocardial infarction (MI), atherosclerosis, hypertension and congestive heart failure symbolize the foremost cause of death in almost all parts of the world. Besides the traditional therapeutic approaches for the management of CVDs, newer innovative strategies are also emerging on the horizon. Recently, gene silencing via small interfering RNA (siRNA) is one of the hot topics amongst various strategies involved in the management of CVDs. The siRNA mechanism involves natural catalytic processes to silence pathological genes that are overexpressed in a particular disease. Also the versatility of gene expression by siRNA deciphers a prospective tactic to down-regulate diseases associated gene, protein or receptor existing on a specific disease target. This article reviews the application of siRNA against CVDs with special emphasis on gene targets in combination with delivery systems such as cationic hydrogels, polyplexes, peptides, liposomes and dendrimers.

Nanomaterial Based Approaches for the Diagnosis and Therapy of Cardiovascular Diseases.

The increasing prevalence and complexity of cardiovascular diseases demand innovative strategies for diagnostic and therapeutic applications to improve patient care/prognoses. Additionally, various factors constrain present cardiovascular therapies, including low aqueous drug solubility, early metabolism, short half-life and drug delivery limitations. The efficient treatment of cardiovascular diseases requires improvement of traditional drug delivery systems. This can be accomplished by using novel nanomaterial that can incorporate diverse bio-actives along with diagnostic agents in a single carrier, referred to as theranostics. This review discusses the state of the art in the applications to diagnosis and therapy of innovative, nanomaterial- based strategies such as lipid based carriers, nanocapsules, magnetic nanoparticles, gold nanoparticles, protein conjugated nanoparticles, dendrimers and carbon-based nanoformulations with a special emphasis on how they can contribute to improving the management of cardiovascular disease.

Recent advances in exosome-based nanovehicles as RNA interference therapeutic carriers

RNA interference (RNAi) therapeutics (siRNA, miRNA, etc.) represent an emerging medicinal remedy for a variety of ailments. However, their low serum stability and low cellular uptake significantly restrict their clinical applications. Exosomes are biologically derived nanodimensional vesicle ranging from a few nanometers to a hundred. In the last few years, several reports have been published demonstrating the emerging applications of these exogenous membrane vesicles, particularly in carrying different RNAi therapeutics to adjacent or distant targeted cells. In this report, we explored the numerous aspects of exosomes from structure to clinical implications with special emphasis on their application in delivering RNAi-based therapeutics. siRNA and miRNA have attracted great interest in recent years due to their specific application in treating many complex diseases including cancer. We highlight strategies to obviate the challenges of their low bioavailability for gene therapy.

Novel nanosystems for the treatment of ocular inflammation: Current paradigms and future research directions

&NA; Ocular discomforts involve anterior/posterior‐segment diseases, symptomatic distress and associated inflammations and severe retinal disorders. Conventionally, the formulations such as eye drops, eye solutions, eye ointments and lotions, etc. were used as modalities to attain relief from such ocular discomforts. However, eye allows limited access to these traditional formulations due to its unique anatomical structure and dynamic ocular environment and therefore calls for improvement in disease intervention. To address these challenges, development of nanotechnology based nanomedicines and novel nanosystems (liposomes, cubosomes, polymeric and lipidic nanoparticles, nanoemulsions, spanlastics and nano micelles) are currently in progress (some of them are already marketed such as Eye‐logic liposomal eye spray@Naturalife, Ireland). Today, it is one of the central concept in designing more accessible formulations for deeper segments of the eyes. These nanosystems has largely enabled the availability of medicaments at required site in a required concentration without inversely affecting the eye tissues; and therefore, attaining the excessive considerations from the formulation scientists and pharmacologists worldwide. The entrapment of drugs, genes, and proteins inside these novel systems is the basis that works at the bio‐molecular level bestows greater potential to eradicate disease causatives. In this review, we highlighted the recent attempts of nanotechnology‐based systems for treating and managing various ocular ailments. The progress described herein may pave the way to new, highly effective and vital ocular nanosystems. Graphical abstract Figure. No caption available.

Recent Advances in Oncological Submissions of Dendrimer

BACKGROUND Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients. METHODS Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body. RESULTS Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation. CONCLUSION Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.

Solid Lipid Nanoparticles for Targeting and Delivery of Drugs and Genes

Most of the biologically active compounds are struggle with low solubility and therefore low bioavailability, biological degradation and inadvertent intrinsic side effects. To overcome such difficulties, the emergence of potential and novel drug carrier system is of supreme importance in terms of their efficient applicability through different routes of administration like skin, oral, topical, parenteral and pulmonary. Considering this, Solid lipid nanoparticles have attracted huge attention for the successful delivery of drugs and genes and also employed as an effective strategy for targeting therapeutics. The potential advantages of solid lipid nanoparticles over other nanoparticles are because of their high biocompatibility, higher drug loading capacity and scalability. In this chapter, we summarize the complete understanding about morphology, methodology, characterization, hybridization and biomedical applications of solid lipid nanoparticles.

Biopolymer-based nanocomposites for transdermal drug delivery

Nanocomposites for the delivery of biomolecules have been explored in several ways since 2010. The production of nanocomposites employing biopolymers, specifically peptides, proteins, hydrocolloids, alginates, pectin, small interfering RNAs, chitosan, and hyaluronic acid, has gained vital research interest. Biopolymers are polymeric materials from biobased or renewable resources and biodegradable in nature. Progress is being made in the prolonged delivery of biopolymers and in the development of particulate delivery systems for alternative routes of administration, such as transdermal route. Transdermal drug delivery system is among the rapidly growing areas of advanced drug delivery research. However, the formidable characteristics of the stratum corneum are of supreme concern that must be resolved for unhesitant delivery of biomolecules through the skin. This chapter expounds the biopolymer-based transdermal delivery systems explored for the development of new medical devices for combating severe skin disorders, which requires localized and enhanced skin penetration to restore normal skin physiology. Another focus of this chapter is to explore the current state of available biopolymers for the development of transdermal therapeutics.

Microsponge Embedded Tablets for Sustained Delivery of Nifedipine

BACKGROUND Nifedipine is a potential therapeutic agent for the treatment of cardiovascular disturbances, although it suffers from short half-life (t1/2, 2 hr). OBJECTIVE To address the problem, we first prepared nifedipine loaded sustained release microsponges and then formulated tablets for effective clinical application and patient compliance. METHOD Preparations of microsponges were carried out using different compositions of nifedipine and polymer (1:1, 1:2 and 1:3 % molar ratio) using emulsion solvent diffusion technique. RESULTS The microsponges with molar ratio 1:3 (formulation code: MF-3) found optimized as revealed by analyzing surface morphology, better powder flow properties (angle of repose; 28.80 ± 0.9, Hausner ratio 1.15 ± 0.2, % compressibility 15.28 ± 0.5% and higher % drug content (80 ± 1.9 %). Different batches of tablets were then formulated incorporating MF-3 microsponges and different proportions (10-50 %) of microcrystalline cellulose and starch as additives. Among tablet formulations, batch composed of 48% of MF-3, 30% of MCC, 20 % of starch and 2 % of talc (TF-33), showed 92.73 ± 2.19 % drug release during 24 hr in vitro release study in comparison to other batches including commercial formulation which was found to be released completely in 20 hr. Further, stability analysis revealed good drug retention of loaded nifedipine as well as consistent in vitro release pattern over a period of 90 days at 40°C and 75% RH. CONCLUSION The microsponge tablet delivery system was found to be superior concerning the therapeutic advantage as well as manufacturing feasibility of nifedipine.

Influence of Drug Properties and Routes of Drug Administration on the Design of Controlled Release System

Abstract To achieve therapeutic drug concentration is not a major task, rather maintaining that concentration for the desired period is clinically more important and is a demanding area of drug delivery science. However, the design of controlled release formulations requires many factors to be considered such as drug delivery rate, delivery duration, physicochemical properties of the drug, nature of excipients, the route of administration, and the dosing interval etc. The objective of the chapter is to provide a complete understanding of several physicochemical properties of the drug that ultimately influence the performance of drug molecule. The chapter includes various aspects of designing controlled release formulations which includes rationale of design, drug properties (molecular weight, pH, pK a , etc.), pharmacokinetic aspects (absorption, distribution, etc.), pharmacodynamic aspects (dosing interval/frequency, patient condition, etc.), and route of drug administration (oral, transdermal, parenteral, etc.).