New Insights in Psoriasis Management using Herbal Drug Nanocarriers.

Psoriasis (Pso) is an autoimmune inflammatory skin disease characterized by red plaques covered in silver scales. The existing treatments provide limited benefits and are associated with certain drawbacks which limit their use. Thus, there is a need to explore more options that are highly target-specific and associated with minimal side effects. Researchers have thoroughly investigated the use of herbal drugs for their therapeutic potential. Preclinical studies demonstrate that phytochemicals such as curcumin, psoralen, and dithranol have antipsoriatic effects. These phytoconstituents inhibit the signalling pathways, such as the interleukin (IL) 23/Th17 axis and IL-36 inflammatory loop involved in the pathogenesis of Pso. These phytoconstituents down-regulate the pro-inflammatory cytokines like IL-17 and tumor necrosis factor (TNF)-α. However, their application in clinical settings is limited due to poor bioavailability and access to target sites. Combining phytoconstituents with modern delivery platforms like nanocarriers can address these shortcomings and improve therapeutic efficacy. This review explores the potential of herbal remedies as a substitute for conventional therapies, emphasizing the clinical trials conducted with these herbal medicines. The paper is supported by the discussion on nanocarriers like liposomes, niosomes, emulsomes, ethosomes, nanostructured lipid carriers, nanoemulsions, and dendrimers that are used to deliver herbal medicines.

pH-triggered polymeric nanoparticles in gel for preventing vaginal transmission of HIV and unintended pregnancy.

Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/ AIDS) and unplanned pregnancy affect female reproductive health globally. A single product providing a dual purpose of HIV prophylaxis and contraception may improve adherence to the therapy. Thus, we formulated a female-centric multipurpose prevention technology (MPT) comprising of nanoparticle loaded vaginal gel formulation acting as a contraceptive and microbicide. Eudragit® S100 nanoparticles of Atazanavir sulphate (ATZ; antiviral) and Fluoxetine hydrochloride (FLX; repurposed spermicide) were prepared for pH dependent drug release and loaded in carrageenan and HPMC K200M gel. The particle size of ATZ and FLX nanoparticles was 396.7 ± 20.64 nm and 226.5 ± 2.08 nm respectively. The in vitro release of the gel formulation in simulated seminal fluid (pH 7.6) showed 96.16% and 95.98% release of ATZ and FLX respectively at the end of 8 h. The in vitro anti-HIV and spermicidal activity of the formulation was above 80% for low drug concentrations. In vivo studies on murine model showed no signs of inflammation or vaginal epithelial injury. Curcumin based imaging confirmed the retention of the formulation in the reproductive tract of mice with minimal leakage. Nanoparticles in gel enabled non-invasive and localised delivery with minimal side effects and can be an effective prophylactic therapy.

2 Receptor Specific Ligand Conjugated Nanocarriers: An Effective Strategy for Targeted Therapy of Tuberculosis.

Tuberculosis (TB) is an ancient chronic disease caused by the bacillus Mycobacterium tuberculosis, which has affected mankind for more than 4,000 years. Compliance with the standard conventional treatment can assure recovery from tuberculosis, but the emergence of drug-resistant strains poses a great challenge for the effective management of tuberculosis. The process of discovery and development of new therapeutic entities with better specificity and efficacy is unpredictable and time-consuming. Hence, delivery of pre-existing drugs with improved targetability is the need of the hour. Enhanced delivery and targetability can ascertain improved bioavailability, reduced toxicity, decreased frequency of dosing and therefore better patient compliance. Nanoformulations are being explored for effective delivery of therapeutic agents, however, optimum specificity is not guaranteed. In order to achieve specificity, ligands specific to receptors or cellular components of macrophage and Mycobacteria can be conjugated to nanocarriers. This approach can improve localization of existing drug molecules at the intramacrophageal site where the parasites reside, improve targeting to the unique cell wall structure of Mycobacterium or improve adhesion to the epithelial surface of intestine or alveolar tissue (lectins). The present review focuses on the investigation of various ligands like Mannose, Mycolic acid, Lectin, Aptamers, etc., installed nanocarriers that are being envisaged for targeting antitubercular drugs.

Mannose-conjugated chitosan nanoparticles for delivery of Rifampicin to Osteoarticular tuberculosis.

Tuberculosis (TB) is a potentially fatal contagious disease and is a second leading infectious cause of death in the world. Osteoarticular TB is treated using standard regimen of 1st and 2nd line anti-tubercular drugs (ATDs) for extensive period of 8-20 months. These drugs are commonly administered in high doses by oral route or by intravenous route, because of their compromised bioavailability. The common drawbacks associated with conventional therapy are poor patient compliance due to long treatment period, frequent and high dosing, and toxicity. This aspect marks for the need of formulations to eliminate these drawbacks. MTB is an intracellular pathogen of mononuclear phagocyte. This attribute makes nanotherapeutics an ideal approach for MTB treatment as macrophages capture nano forms. Polymeric nanoparticles are removed from the body by opsonization and phagocytosis, which forms an ideal strategy to target macrophage containing mycobacteria. To further improve targetability, the nanoparticles are conjugated with ligand, which serves as an easy substrate for the receptors present on the macrophage surface. The purpose of present work was to develop intra-articular injectable in situ gelling system containing polymeric nanoparticles, which would have promising advantages over conventional method of treatment. The rationale behind formulating nanoparticle incorporated in situ gel-based system was to ensure localization of the formulation in intra-articular cavity along with sustained release and conjugation of nanoparticles with mannose as ligand to improve uptake by macrophages. Rifampicin standard ATD was formulated into chitosan nanoparticles. Chitosan with 85% degree of deacetylation (DDA) and sodium tripolyphosphate (TPP) as the crosslinking agent was used for preparing nanoparticles. The percent entrapment was found to be about 71%. The prepared nanoparticles were conjugated with mannose. Conjugation of ligand was ascertained by performing Fourier transformed infrared spectroscopy. The particle size was found to be in the range of 130-140 nm and zeta potential of 38.5 mV. Additionally, we performed scanning electron microscopy to characterize the surface morphology of ligand-conjugated nanoparticles. The conjugated chitosan nanoparticles were incorporated into in situ gelling system comprising Poloxamer 407 and HPMC K4M. The gelling system was evaluated for viscosity, gelling characteristics, and syringeability. The drug release from conjugated nanoparticles incorporated in in situ gel was found to be about 70.3% at the end of 40 h in simulated synovial fluid following zero-order release kinetics. Based on the initial encouraging results obtained, the nanoparticles are being envisaged for ex vivo cellular uptake study using TB-infected macrophages.

Vaginal siRNA delivery: overview on novel delivery approaches.

Increasing incidences of sexually transmitted disease including human papillomavirus (HPV), herpes simplex virus (HSV), and human immunodeficiency virus (HIV) infection in women have triggered the need for developing user-friendly potential prophylactic approach. Presently, although several therapeutic moieties are in place but none of them have prophylactic action, they are confined to provide symptomatic relief to the patient-researchers which have now recognized the need for discovering efficient topical prophylactic agents. One of these with great potential topical microbicide uncovered is vaginal delivery of small interfering RNA (siRNA). siRNA delivery involves silencing gene expression in a sequence specific manner in causative agent thereby exhibiting microbicide activity. However, the mucosal barrier and physiological changes in vagina such as pH and variable epithelial layer thickness during menstrual cycle serve as major hurdles for efficient delivery and cellular uptake of siRNA. In order to enhance vaginal delivery of siRNA, nanocarrier systems like lipid-based delivery systems, macromolecular systems, polymeric nanoparticles, aptamer and cell-penetrating peptides have been investigated widely until date. The present article elaborates on various nanocarriers and their promising outcomes at preclinical stage and future implications of nanocarrier-based siRNA vaginal delivery. Graphical abstract Overview on barriers to the delivery of siRNA by vaginal route and nanocarrier envisaged until date for enhancing efficient delivery of siRNA.

Vaginal multipurpose prevention technologies: promising approaches for enhancing women's sexual and reproductive health.

Introduction: Multipurpose prevention technologies (MPTs) have the potential to avert multiple concomitant sexual and reproductive health issues in women such as sexually transmitted infections and unintended pregnancy. MPTs incorporate one or more active pharmaceutical ingredients in a single product, which adds more convenience for users and may promote increased adherence. Various vaginal dosage forms/delivery systems have been studied for designing MPTs. However, several challenges remain that are mainly related to requirements of individual drugs or intended multiple applications.Areas covered: This review focuses on the emerging need and development of vaginal MPTs. It illustrates numerous examples that are currently in the preclinical and clinical development pipeline, highlighting the concept behind vaginal MPTs. The article also highlights the challenges associated with formulation design and development, including regulatory issues that need to be addressed.Expert opinion: Vaginal MPTs present great potential to empower women with novel, efficient, and safe products for protection against sexually transmitted infections and unintended pregnancy. However, several technological issues and regulatory gaps still need to be addressed in order to meet real-world needs.

Current and novel approaches for control of dental biofilm.

Insights in oral demographics have revealed that a significant percentage of population faces chronic incidences of oral diseases. The innervation of these oral manifestations is required because untreated conditions may lead to bone loss in the oral cavity and systemic complications. Conventional treatments include surgery of the affected area followed by its management and/or treatment with antibiotics. However, widely used antibiotics like Triclosan have serious side effects including down-regulation of oral keratinocytes and fibroblasts. Thus, novel treatments with more targeted approaches have been under investigation. Treatment modalities like Viral mediated gene delivery, liposomes, nanoparticles, and nanobubbles not only help in management of oral diseases but also aid in reducing the biofilm formed due to bacterial bioburden in the areas less accessible through oral and conventional means. This review focuses on the limitation of conventional treatments and highlights the recent investigations in the use of the novel treatment approaches in order to increase the patient compliance and alleviation of side effects. The authors have also tried to emphasize on the future perspectives of glucansucrase inhibitors, photodynamic therapy and probiotics as targeted drug delivery systems. However, further investigations are necessary for implementation of these novel approaches in the clinical setup.