Application of quality-by-design approach to optimize diallyl disulfide-loaded solid lipid nanoparticles.

The current work was carried out by the principles of quality-by-design approach to develop an optimized solid lipid nanoparticles (SLNs) formulation of diallyl disulfide (DADS) through systematic statistical study. And its antitumor activity of DADS was also evaluated on breast cancer cell lines. To understand the effect of formulation variables (critical parameters) on the responses (critical quality attributes) of SLN, a 3-factor, 3-level Box-Behnken design, was explored to predict the responses such as particle size (Y1) and % entrapment efficiency (EE) (Y2) when concentration of surfactant (X1), amount of lipid (X2), and volume of solvent (X3) were selected as independent variables. Particle size analysis revealed that all the batches were within the nanometer range. DADS was released from the SLN much more rapidly at pH 4.5 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. The cytotoxicity, reactive oxygen species (ROS), determination revealed that the antitumor activity of DADS is enhanced with SLN compared to DADS-free drug, and apoptosis is the mechanism underlying the cytotoxicity. The present study indicated the remarkable potential of DADS-SLN in enhancing the anticancer effect of DADS in breast cancer cells in vitro.

Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing.

Diabetic wounds are a common complication in patients with diabetes that often lead to amputation. Although the pathophysiology of diabetic wound is multifactorial, chronic inflammation and lack of tissue regeneration leads to impair wound healing in diabetes. Application of curcumin (CUR) which is a well-known anti-inflammatory and antioxidant agent could be better strategy in diabetic wound healing. However, low bioavailability and poor stability of CUR hinders its application. Hence, in present study a novel nanohybrid scaffold has been prepared by incorporating CUR in chitosan nanoparticles (CSNPs) to improve stability and solubility followed by impregnation of prepared CUR-CSNPs into collagen scaffold (nanohybrid scaffold) for better tissue regeneration application. The prepared CUR-CSNPs were evaluated for particle size, zeta potential, SEM, differential scanning calorimetry and X-ray powder diffraction studies and the novel nanohybrid is evaluated for morphology, biodegradability, biocompatibility, in vitro drug release and in vivo wound healing studies. The results of NPs evaluation suggest the better stability and solubility of CUR. The nanohybrid scaffold showed good in vitro characteristics in terms of better water uptake, biocompatibility and sustained drug availability. The results of in vivo wound closure analysis revealed that nanohybrid scaffold treated wounds contracted significantly (p<0.001) faster than the wounds from the control and placebo scaffold groups. Further, the obtained results suggest that complete epithelialization with thick granulation tissue formation occur in nanohybrid scaffold group, whereas lack of compact collagen deposition in placebo scaffold group and presence of inflammatory cells in control group was observed. Hence, the present study suggests that the synergistic combination of CUR (anti-inflammatory and anti-oxidant), chitosan (sustain drug carrier, wound healing) and collagen (established wound healer as scaffold) is a promising strategy to address various pathological manifestations of diabetic wounds and have better wound healing capability.

Current and emerging therapies in the management of diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcers are one of the major causes of mortality in diabetic patients. Very few drugs and therapies have regulatory approval for this indication and several agents from diverse pharmacological classes are currently in various phases of clinical trials for the management of diabetic foot ulcers. SCOPE: The purpose of this review is to provide concise information of the drugs and therapies which are approved and present in clinical trials. REVIEW METHODS: This review was carried out by systematic searches of relevant guidelines, patents, published articles, reviews and abstracts in PubMed/Medline, Web of Science, clinicaltrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Google Scholar of all English language articles up to 1 March 2015. The following search terms were used: diabetes, diabetic foot, diabetic foot ulcer, diabetic wound, diabetic foot infections, wound management, randomized controlled trials, approved treatments, new treatments and clinical trials. CONCLUSIONS: The various drugs and therapies for the management of diabetic foot ulcers comprise antibiotics, neuropathic drugs, wound dressings, skin substitutes, growth factors and inflammatory modulators. The majority of these therapies target the treatment of diabetic foot ulcers to address the altered biochemical composition of the diabetic wound. However, no single treatment can be definitively recommended for the treatment of diabetic foot ulcers.