Tacrolimus encapsulated mesoporous silica nanoparticles embedded hydrogel for the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a repetitive inflammatory skin disorder with limited treatment options. Innovative targeted therapies are gaining significant interest and momentum towards disease control including better ways to deliver drugs topically. Tacrolimus is one such compound which is used to manage moderate to severe AD without causing atrophy which is one of the common side effects of steroids. However, Tacrolimus suffers from poor solubility and retention in the skin when used alone in hydrogel. Therefore, we have prepared Tacrolimus loaded mesoporous silica nanoparticles (TMSNs) to overcome the issues related to its solubility and effective topical delivery. Mesoporous silica nanoparticles (MSNs) were synthesized using sol gel technique and surface functionalized using amino (-NH2+) and phosphonate (-PO3-) groups. Tacrolimus was loaded into MSNs and the particles were characterized for particle size (TEM and DLS), zeta potential (DLS), solubility studies, FTIR, TGA, XRD, BET and cytotoxicity studies. Water solubility of Tacrolimus was increased by 7 folds with phosphonate functionalized MSNs compared to free Tacrolimus. Further the TMSNs were incorporated in to carbopol gel, and the gel formulation was evaluated for various gel characterization tests (pH, spreadability, viscosity), in vitro tests (drug release, permeability studies) and in vivo tests (skin irritation study and efficacy studies) using 1-Fluoro-2,4-dinitrobenzene (DNFB) induced dermatitis in Balb/c mice. Results of in vitro and in vivo study showed that TMSNs loaded gel showed significantly higher amount of Tacrolimus retained (ex vivo - rat skin) and much higher reduction in ear thickness and improved histology (in vivo - in mice). Our data collectively suggest that MSNs incorporated hydrogel as a promising new formulation strategy for topical delivery of poorly soluble drugs.

Emerging Nanomedicines for the Treatment of Atopic Dermatitis.

Globally, the prevalence of Atopic dermatitis (AD) is significantly increasing and affecting around 20% of population including children. Complex interactions amongst abnormality in epidermal barrier function, environment, infectious agents and immunological defects are considered as key factors in the pathogenesis of AD. Although the role of oxidative stress has been studied in some skin diseases, investigation of the same in AD is intermittent. Calcineurin inhibitors and/or topical corticosteroids are currently available; however, it causes atrophy of the skin, burning sensation, and systemic side effects which leads to poor patient compliance. These limitations provoke the strong need to develop an innovative approach in managing AD. Nanomaterials for effective drug delivery to skin conditions such as AD have attracted a lot of attention owing to its ability to encapsulate, protect, and release the cargo at the diseased skin site. However, there are lots of unmet challenges especially in terms of development of non-toxic formulations and clinical translation of established nanomedicines in the form of accessible products. Numerous formulations have emerged as carrier for poorly soluble and permeable drugs, viz., lipidic, polymeric, metal, silica, liposomes, hydrocarbon gels and this field is evolving. This review is intended to provide an insight incidences associated with pathophysiology of AD and challenges with existing treatments of AD. Focus is kept on reviewing current development and emerging nanomedicines for effective treatment of AD. The review also inculcates merits of several nanomedicines in overcoming challenges of existing products and its future implications.

Two dimensional carbon based nanocomposites as multimodal therapeutic and diagnostic platform: A biomedical and toxicological perspective.

Graphene based nanocomposites have revolutionized cancer treatment, diagnosis and imaging owing to its good compatibility, elegant flexibility, high surface area, low mass density along with excellent combined additive effect of graphene with other nanomaterials. This review inculcates the type of graphene based nanocomposites and their fabrication techniques to improve its properties as photothermal and theranostic platform. With decades' efforts, many significant breakthroughs in the method of synthesis and characterization in addition to various functionalization options of graphene based nanocomposite have paved a solid foundation for their potential applications in the cancer therapy. This work intends to provide a thorough, up-to-date holistic discussion on correlation of breakthroughs with their biomedical applications and illustrate how to utilize these breakthroughs to address long-standing challenges in the clinical translation of nanomedicines. This review also emphasizes on graphene based nanocomposites based toxicity concerns pertaining to delivery platforms.