siRNA-Based Novel Therapeutic Strategies to Improve Effectiveness of Antivirals: An Insight.

Since the ground-breaking discovery of RNA interference (RNAi), scientists have made significant progress in the field of small interfering RNA (siRNA) treatments. Due to severe barriers to the therapeutic application of siRNA, nanoparticle technologies for siRNA delivery have been designed. For pathological circumstances such as viral infection, toxic RNA abnormalities, malignancies, and hereditary diseases, siRNAs are potential therapeutic agents. However, systemic administration of siRNAs in vivo remains a substantial issue due to a lack of "drug-likeness" (siRNA are relatively larger than drugs and have low hydrophobicity), physiological obstacles, and possible toxicities. This write-up covers important accomplishment in the field of clinical trials and patents specially based of siRNAs using targeting viruses. Furthermore, it offers deep insight of nanoparticle applied for siRNA delivery and strategies to improve the effectiveness of antivirals.

Nano-strategies as Oral Drug Delivery Platforms for Treatment of Cancer: Challenges and Future Perspectives.

Oral drug administration is the oldest and widely used method for drug administration. The objectives behind developing an oral drug delivery for the treatment of cancer are to achieve low cost treatment by utilizing novel techniques to target cancer through gut-associated lymphoid tissue (GALT) and to enhance patient comfort and compliance through a hospital-free treatment leading to "Chemotherapy at Home." Unfortunately, due to the physiological environment of the GIT and physicochemical properties of drug candidate, the efficacy of oral drug delivery methods is limited in the treatment of cancer. Due to their low hydrophilicity, high P-gp efflux and restricted intestinal permeability most of the anti-cancer drugs fail to achieve oral bioavailability. The review focuses on the efforts, challenges, opportunities and studies conducted by scientists worldwide on the oral administration of anticancer medications via nanocarriers such as liposomes, SLNs and dendrimers, because of their potential to overcome the epithelial barrier associated with GALT, as well as the applications of different polymers in targeting the cancer. The oral delivery can set newer horizons in cancer therapy to make it more patient friendly.

Small interfering RNA (siRNA) as a potential gene silencing strategy for diabetes and associated complications: challenges and future perspectives.

Objective: This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence specific genes in various cell types, including those involved in diabetes complications. Significance: Diabetes, a prevalent and severe condition, poses life-threatening risks due to elevated blood glucose levels. It results from inadequate insulin production by the pancreas or ineffective insulin utilization by the body. Recent research suggests siRNA could hold promise in addressing diabetes complications. Methods: In this review, we discussed several subjects, including diabetes; its function, and common treatment options. An in-depth analysis of gene silencing method for siRNA and role of siRNA in diabetes, focusing on its impact on glucose homeostasis, diabetic retinopathy, wound healing, diabetic nephropathy and peripheral neuropathy, diabetic foot ulcers, diabetic atherosclerosis, and diabetic cardiomyopathy. Result: siRNA-based treatment has the potential to target specific genes without disrupting several other endogenous pathways, which decreases the risk of off-target effects. In addition, siRNA has the capability to provide long-term efficacy with a single dose which will reduce treatment options and enhance patient compliance. Conclusion: In the context of diabetic complications, siRNA has been explored as a potential therapeutic tool to modulate the expression of genes involved in various processes associated with diabetes-related issues such as Diabetic Retinopathy, Neuropathy, Nephropathy, wound healing. The use of siRNA in these contexts is still largely experimental, and challenges such as delivery to specific tissues, potential off-target effects, and long-term safety need to be addressed. Additionally, the development of siRNA-based therapies for clinical use in diabetic complications is an active area of research. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01405-7.

Development of fucoidan/polyethyleneimine based sorafenib-loaded self-assembled nanoparticles with machine learning and DoE-ANN implementation: Optimization, characterization, and in-vitro assessment for the anticancer drug delivery.

This study aims to develop sorafenib-loaded self-assembled nanoparticles (SFB-SANPs) using the combined approach of artificial neural network and design of experiments (ANN-DoE) and to compare it with other machine learning (ML) models. The central composite design (CCD) and ML algorithms were used to screen the effects of concentrations of both the polymers (polyethyleneimine and fucoidan) on the outcome responses, i.e., particle size and entrapment efficiency with defined constraints. The prediction from different ML models (bootstrap forest, K-nearest neighbors, artificial neural network, generalized regression-lasso and support vector machines) were compared with ANN-DoE model. The ANN-DoE model showed better accuracy and predictability and outperformed all the other models. This depicted that the concept of using ANN and DoE combination approach provided the best, uncomplicated and cost-effective way to optimized the nanoformulations. The optimized formulation generated from the ANN-DoE combined model was further evaluated for characterization and anticancer activity. The optimized SFB-SANPs were prepared using the polyelectrolyte complexation method with Polyethyleneimine (PEI) as a cationic polymer and fucoidan (FCD) as an anionic. The SFB-SANPs were nanometric in size (280.4 ± 0.089 nm) and slightly anionic in nature (zeta potential = -6.03 ± 0.92 mV) with an encapsulation efficiency of 95.56 ± 0.30 %. The drug release from SFB-SANPs was controlled and sustained in the cancer microenvironment (pH 5.0). The SFB-SANPs were compatible with red blood cells (RBCs), and the % hemolysis was found to be <5.0 %. The anticancer activity of the SFB-SANPs exhibited an IC50 at 2.017 ± 0.516 µM against MDMB-231 cells, showing a significantly high inhibitory effect on breast cancer cell lines. Therefore, the nanocarriers developed using various ML tools inherit a huge promise in anticancer drug delivery.

Dual Delivery of Fluticasone Propionate and Levocetirizine Dihydrochloride for the Management of Atopic Dermatitis Using a Microemulsion-Based Topical Gel.

The current study investigates the potential for topical delivery of a fluticasone propionate (FP) and levocetirizine dihydrochloride (CTZ)-loaded microemulsion (ME) for the management of atopic dermatitis. Various microemulsion components were chosen based on their solubility and emulsification capabilities, and the ternary phase diagram was constructed. A total of 12 microemulsion formulations were screened for various attributes like vesicle size, polydispersity index, ζ-potential, percent transmittance, density, and pH. The average globule size and ζ-potential of FP and levocetirizine-containing ME were 52.12 nm and -2.98 ζ-potential, respectively. Transmission electron microscopy confirmed the spherical nature of the globules. The developed system not only controlled the release of both drugs but also enhanced the efficacy of the drugs on a rodent model. Histopathological studies confirmed the safety of the developed system. The present findings provide evidence for a scalable and simpler approach for the management of atopic dermatitis.

Road map to the treatment of neglected tropical diseases: Nanocarriers interventions.

Neglected tropical disease (NTD) is a set of 20 deadliest endemic diseases which shows its presence in most of the developing countries worldwide. Nearly 1 billion of the population are affected by it and suffered from poverty yearly. These diseases offer their own unique challenges and limitations towards effective prevention and treatment methods. Neglected tropical diseases are severe infections they may not kill the patient but debilitate the patient by causing severe skin deformities, disfigurement and horrible risks for several infections. Existing therapies for neglected diseases suffer from the loopholes like high degree of toxicity, side effects, low bioavailability, improper targeting and problematic application for affected populations. Progress in the field of nanotechnology in last decades suggested the intervention of nanocarriers to take over and drive the research and development to the next level by incorporating established drugs into the nanocarriers rather than discovering the newer drugs which is an expensive affair. These nanocarriers are believed to be a sure shot technique to fight infections at root level by virtue of its nanosize and ability to reach at cellular level. This article highlights the recent advances, rationale, targets and the challenges that are being faced to fight against NTDs and how the novel therapy tactics are able to contribute to its importance in prevention and treatment of NTDs.