Emerging Pathophysiological Targets of Psoriasis for Future Therapeutic Strategies.

Psoriasis is a chronic autoimmune skin disorder which involves complex interactions between genes, keratinocytes, T-cells and inflammatory cells. It affects 2-3% population worldwide. Molecular biology and cellular immunology of psoriasis, when linked with biotechnology and genetic studies can help researchers to understand the pathophysiology of psoriasis. T-cells activation, keratinocyte hyperproliferation, and angiogenesis are the core mechanisms entailed in the development of psoriasis lesion. Investigators are trying to overcome the challenges of complex pathophysiology pathways involved in this disorder. The different possible hypotheses for its pathophysiology such as growth factors, enzymes, inflammation, and genetic factors mediated pathophysiology have been described in the present review paper in detail. Clinically available drugs only control the symptoms of psoriasis but are not effective for the treatment of the disorder completely and are also associated with some side effects such as itching, renal disorders, hematologic, nonmelanoma skin cancer, pulmonary, gastrointestinal toxicity, etc. This paper made an effort to understand the pathophysiological targets, discuss the research done so far and the treatments available for the effective management of psoriasis.

Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety.

The study aims at formulation and optimization brain targeted nanoparticles (NP) of Rivastigmine (RT) to improve its therapeutic potential and to verify its safety profile. The NP were optimized using a two factor three level (3(2)) central composite design aiming to minimize particle size; maximize zeta potential and drug entrapment efficiency of NP. The optimized formulation (cRTNP) was evaluated using in vitro drug release study; in vivo behavioral, and biochemical and maximum tolerated dose (MTD) study. The optimized formulation evidenced a significant reversal of scopolamine-induced amnesia by Tween 80(®) coated nanoparticles as compared to both pure RT as well as uncoated nanoparticles. The MTD of RT was increased by 10% by formulating them as cRTNP. Thus, formulation of RT as cRTNP improved the therapeutic and safety profile of RT.

Evaluation of safety and efficacy of brain targeted chitosan nanoparticles of minocycline.

The aim of present study was to evaluate the antidepressant-like effects of minocycline hydrochloride (MH); enhance this effect using nanoparticulate drug delivery system; and further evaluate their safety by determining maximum tolerated dose (MTD). Pure drug MH, MH loaded nanoparticles (MHNP) and Tween 80(®) coated MH encapsulated nanoparticles (cMHNP) were explored for antidepressant-like activity in terms of immobility period using despair swim test (DST) and tail suspension test (TST) in mice (dose equivalent to 100mg/kg MH, i.p.). For MTD determination, Wistar rats were treated with gradual increasing doses of MH and cMHNP orally for 28 consecutive days and observed for body weight, weight indices (WI), behavioral, biochemical and histopathological changes until MTD was found. In mice, MH treatment showed antidepressant-like activity and cMHNP treatment significantly improved this effect. On the other hand, no significant effect was observed for MHNP treated group. However, administration of MH in any case did not produce locomotor activation, suggesting that the antidepressant-like effects of MH may not be attributed to the enhanced locomotion. The MTD was found to be 319mg/kg for MH and 350mg/kg for cMHNP (350mg/kg). Thus surface modified nanoparticles (cMHNP) improved the therapeutic efficacy as well as safety of MH.