Recent Developments in Proniosomal Transdermal Drug Delivery: An Overview.

Proniosomes are the stable carriers used for transdermal application as compared to other vesicular delivery systems like niosomes and liposomes. Oral administration of a drug is associated with severe GIT irritation and first-pass metabolism. The vesicular drug delivery system includes the basic concept of niosomes and proniosomes which describes their mechanism of action, structural formation, interactive study with skin, composition, and method of preparation. Gels contain a high aqueous component as compared to ointment and creams, due to which they can dissolve high concentrations of drugs, and thus help the drug to migrate easily through a vehicle, due to which, gels are considered to be superior in terms of use and patient compliance. This review will focus on the up-to-date research developments in the use of proniosomes, which are applicable to various diseases. Proniosomes are prepared mainly by different concentrations of nonionic surfactants, cholesterol, and lecithin by entrapping hydrophobic as well as hydrophilic drugs. In earlier studies, it was found that the non-ionic surfactants and phospholipids provided higher penetration and it has also been found that some phospholipids have the ability to fluidize the lipid bilayers of the stratum corneum and diffuse through it. In the future, proniosomes may gain more importance in the area of melanoma, brain targeting, protein and peptide drug delivery, gene delivery, hematological drug delivery, and also in cosmetics, and nutraceuticals.

Design and Development of Crystallo-co-agglomerates of Ritonavir for the Improvement of Physicochemical Properties.

OBJECTIVES: The aim of the present study was to obtain CCA of ritonavir to improve the solubility, dissolution rate, and other physicochemical properties. MATERIALS AND METHODS: Ritonavir agglomerates were prepared using the CCA technique. Acetone-water containing HPMC K-15, PEG-6000, PVP K-30 was used as the crystallization medium. The agglomerates were evaluated for saturation solubility, micromeritic properties, yield, and drug content. The agglomerates were also characterized using FTIR, DSC, XRPD and SEM. RESULTS: The growth of particle size and the spherical form of the agglomerates resulted in the formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to the fragmentation that occurred during compression. DSC and XRD studies showed that ritonavir particles crystallized in the presence of HPMC, PEG-6000, PVP K-30 and diluents did not undergo structural modifications. The solubility and dissolution rate of ritonavir agglomerates were improve compare to pure ritonavir. CONCLUSION: CCA was successfully applied to improve the physicochemical properties of ritonavir.

Effect of piperine on inhibition of FFA induced TLR4 mediated inflammation and amelioration of acetic acid induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medicinal use. Piperine exhibits antidepressant, hepatoprotective, anti-metastatic, anti-thyroid, immunomodulatory, antitumor and anti-inflammatory activities, However its therapeutic potential in amelioration of ulcerative colitis and the underlying mechanism for anti-inflammatory activity remains unknown.The objective of the present investigation was to unravel the therapeutic potential of piperine on amelioration of IBD using acetic acid induced experimental animal model for ulcerative colitis and to determine the role of TLR4 receptor in signalling pathway of inflammatory gene expression in ulcerative colitis. MATERIALS AND METHODS: We induced colitis using acetic acid (150µl of 5% once, intrarectally) in mice and estimated disease activity index (DAI), which took into account weight loss, stool consistency, and occult/gross bleeding. Colon length, spleen weights, ulcer area and ulcer index were measured; histological changes were observed by H&E staining. Effect of piperine on various antioxidant parameter of mice colon such as tissue myeloperoxidase (MPO) accumulation, SOD concentrations, reduced GSH and lipid peroxidation were determined. Pro-inflammatory mediators, namely, nitric oxide (NO), tumour necrosis factor-α (TNF-α) were determined by a TNF-α ELISA kit obtained from Thermo fisher scientific India Pvt. Ltd. Effect of piperine on haematological parameters of mice in acetic acid induced IBD was also determined which involves the estimation of FFA using a commercial free fatty acid fluorometric assay kit. RESULT: Piperine significantly attenuated acetic acid induced DAI score which implies that it suppresses weight loss, diarrhoea, gross bleeding and infiltration of immune cells. Piperine administration also effectively and dose dependently prevented shortening of colon length and enlargement of spleen size. Histological examination indicated that piperine reduces oedema in sub-mucosa, cellular infiltration, reduced haemorrhages and ulceration as compare to acetic acid induced colitis in mice. Furthermore piperine inhibited abnormal secretion of pro-inflammatory mediators namely NO, cytokines TNF-α and reduces FFA induced TLR4 mediated inflammation. CONCLUSION: These results suggest that piperine has an anti-inflammatory effect at colorectal sites that is due to down- regulations of the productions and expression of inflammatory mediators and it also reduces FFA induced TLR4 mediated inflammation. Thus it may have therapeutic potential on amelioration of IBD.