Novel drug delivery systems in topical treatment of psoriasis: Rigors and vigors

Psoriasis is a chronic inflammatory skin disorder that may drastically impair the quality of life of a patient. Among the various modes of treatments for psoriasis, topical therapy is most commonly used in majority of patients. The topical formulations based on conventional excipients could serve the purpose only to a limited extent. With the advent of newer biocompatible and biodegradable materials like phospholipids, and cutting-edge drug delivery technologies like liposomes, solid lipid nanoparticles (SLNs), microemulsions, and nanoemulsions, the possibility to improve the efficacy and safety of the topical products has increased manifold. Improved understanding of the dermal delivery aspects and that of designing and developing diverse carrier systems have brought in further novelty in this approach. Substantial efforts and the consequent publications, patents and product development studies on the subject are the matter of interest and review of this article. However, majority of the work is related to the preclinical studies and demands further clinical assessment in psoriasis patients

Systematic Development of Drug Nanocargos Using Formulation by Design (FbD): An Updated Overview

Nanostructured drug delivery formulations have lately gained enormous attention, contributing to their systematic development. Issuance of quality by design (QbD) guidelines by ICH, FDA, and other federal agencies, in this regard, has notably influenced the overall development of drug products, enabling holistic product and process understanding. Owing to the applicability of QbD paradigms, a science lately christened as formulation by design (FbD) has been dedicated exclusively to QbD-enabled drug product development. Consisting of the principal elements of design of experiments (DoE), quality risk management (QRM), and QbD-enabled product comprehension as the fundamental tools in the implementation of FbD, a variety of drug nanocargos have been successfully developed with FbD paradigms and reported in the literature. FbD aims to produce novel and advanced systems utilizing nominal resources of development time, work effort, and money. A systematic FbD approach envisions the entire developmental path through pivotal milestones of risk assessment, factor screening and optimization (both using appropriate experimental designs), multivariate statistical and optimum search tools, along with response surface modeling, usually employing suitable computer software. The design space is one of the fundamental elements of FbD providing the most sought-after regulatory flexibility to pharma companies, postapproval. The present paper provides a bird's eye view of the fundamental aspects of FbD terminology, methodology, and applications in the development of a wide range of nanocargos, as well as a discussion of trends from both technological and regulatory perspectives

Lysine-Based C₆₀-Fullerene Nanoconjugates for Monomethyl Fumarate Delivery: A Novel Nanomedicine for Brain Cancer Cells

In the present study, water-soluble lysine-based C₆₀-fullerene nanoconjugates (CF-LYS-TEG-MMF) were synthesized using a biodegradable linker for the better delivery of monomethyl fumarate (MMF) employing Prato reaction. CF-LYS-TEG-MMF resulted in enhanced cytotoxicity on neuroblastoma cells, meanwhile found to be substantially biocompatible to erythrocytes. The designed nanoconjugate exhibited a pH-based drug release pattern, minimizing the leaching of drug at plasma pH. However, the carrier offered maximum drug release at cancer cell pH, indicating huge promise in internalization of drug molecules at the site of target. The pharmacokinetics of MMF in rodents was significantly improved in terms of enhanced bioavailable drug fraction in the central compartment, reduced drug clearance, elevated plasma concentrations and prolonged biological residence of drug. Enhanced in vitro efficacy in SH-SY5Y neuroblastoma cells, improved erythrocyte compatibility, high drug loading, and conducive pharmacokinetic profile by CF-LYS-TEG-MMF offers a huge promise in brain drug delivery, dose reduction, and dosage-regimen alteration for the management of brain tumors employing MMF

Integrating genomics and genome editing for orphan crop improvement: a bridge between orphan crops and modern agriculture system

ABSTRACTDomestication of orphan crops could be explored by editing their genomes. Genome editing has a lot of promise for enhancing agricultural output, and there is a lot of interest in furthering breeding in orphan crops, which are sometimes plagued with unwanted traits that resemble wild cousins. Consequently, applying model crop knowledge to orphan crops allows for the rapid generation of targeted allelic diversity and innovative breeding germplasm. We explain how plant breeders could employ genome editing as a novel platform to accelerate the domestication of semi-domesticated or wild plants, resulting in a more diversified base for future food and fodder supplies. This review emphasizes both the practicality of the strategy and the need to invest in research that advances our understanding of plant genomes, genes, and cellular systems. Planting more of these abandoned orphan crops could help alleviate food scarcities in the challenge of future climate crises

Enhanced Brain Delivery of Dimethyl Fumarate Employing Tocopherol-Acetate-Based Nanolipidic Carriers: Evidence from Pharmacokinetic, Biodistribution, and Cellular Uptake Studies

Dimethyl fumarate (DMF) is an approved drug for the management of relapsing multiple sclerosis. Despite efficacy, DMF is also reported to be a challenging drug owing to concerns like gastrointestinal tract flushing, multiple dosing, lower brain permeability, less patient compliance, and economic hurdles. The present study aims to develop DMF-tocopherol acetate nanolipidic carrier (NLCs) to enhance brain permeability and improve the gastric tolerance. The developed DMF-tocopherol acetate NLCs offered an average size of 69.70 nm, PDI of 0.317, and a zeta potential of −9.71 mV. Higher drug entrapment (90.12%) and drug loading (20.13%) assured controlled drug release behavior both in gastric and intestinal pH. Cellular uptake studies on Caco-2 and SH-SY5Y monolayers confirmed better intestinal absorption and neuronal uptake of the developed system, which was further corroborated by the pharmacokinetic and biodistribution studies. The oral bioavailability was enhanced by 4.09 times and brain availability was substantially improved vis-à-vis plain drug. The findings are promising and offer preclinical evidence for better brain availability of DMF, which can be exploited in the better management of diseases like multiple sclerosis