Novel anionic polymer as a carrier for CNS delivery of anti-Alzheimer drug.

Natural and plant-based polymers could be used for control release of drugs and also helps in targeting drug to the site of action. The main objective of present work was to check the feasibility of plant-based, namely, mango gum polymeric nanoparticles (NPs) as a carrier for central nervous system (CNS) delivery using model drug donepezil (DZP). The NPs were prepared by modified ionic gelation method and emulsion cross-linking method. Zeta sizer results showed that the diameter of NPs was about 90-130 nm. The polymeric DZP-loaded NPs were almost spherical in shape, as revealed by transmission electron microscopy (TEM). On increasing concentration of NPs suspension from 50 µg/ml to 5000 µg/ml there was no significant increase in % hemolysis. In vivo studies showed that brain targeting was achieved. So on the basis of above results, the extracted water soluble fraction of mango gum is a suitable candidate for brain delivery in the form of nanoformulations.

Physicochemical characterization and toxicological evaluation of plant-based anionic polymers and their nanoparticulated system for ocular delivery.

The water-soluble fractions of mucilages and gum from the seeds of fenugreek, isphagula and mango bark exudate were isolated, purified and characterized using X-ray diffraction (XRD) spectrometry, Fourier transform infrared spectroscopy (FT-IR), maldi/GC-MS, elemental analysis, 1D ((1)H and (13)C) and 2D (HMQC, COSY) nuclear magnetic resonance spectroscopy (NMR). The fenugreek mucilage was identified to be a galactomannan chain consisting of 4 units of galactose attached to the backbone of 6 mannose units in 1:1.5 ratio. The isphagula mucilage was identified to be an arabinoxylan polysaccharide chain consisting of 4 units of arabinofuranose attached to the backbone of 9 xylopyrannose units in 1:3 ratio. The mango gum showed the presence of amylose, α-arabinofuranosyl and ß-galactopyranosyl, respectively. The characterized mucilages and gum were individually formulated into nanoparticulate system using their complementarily charged polymer chitosan. The particles were observed to be spherical in shape in the range of 61.5-90 nm having zetapotential between 31 and 34 mV and PDI of 0.097-0.241. The prepared nanoparticles were observed to be nonirritant and nontoxic in vitro and in vivo upto 2000 µg/ml. Therefore, these mucilages and gum can be the alternatives of anionic polymers for the ocular drug delivery system.

Development and biological evaluation of Gymnema sylvestre extract-loaded nonionic surfactant-based niosomes.

AIM: To develop and characterize Gymnema sylvestre extract-loaded niosomes using nonionic surfactants, and to evaluate their antihyperglycemic efficacy in comparison with the parent extract. MATERIALS & METHODS: Nonionic surfactant-based G. sylvestre extract-loaded niosomes were prepared using the thin-film hydration method. The optimized formulation was screened for entrapment efficiency of the constituents, as well as other parameters such as release kinetics, vesicle size, zeta-potential and stability studies. The parent extract and optimized niosomal formulation were evaluated for their antihyperglycemic potential in an alloxan-induced diabetic animal model. RESULTS: Niosomes prepared using Span™ 40 (SD Fine Chemicals Ltd, Mumbai, India) provided sterically stable vesicles 229.5 nm in size with zeta-potential and entrapment efficiency of 150.86 mV and 85.3 ± 4.5%, respectively. The surface morphology of vesicles was confirmed to be spherical by scanning electron microscopy studies. An in vitro release study demonstrated 77.4% of phytoconstituents release within 24 h. The niosome formulation demonstrated significant blood glucose level reduction in an oral glucose tolerance test, and increased antihyperglycemic activity compared with the parent extract in an alloxan-induced diabetic model. CONCLUSION: This study reveals the merits of G. sylvestre extract-loaded niosomes, and justifies the potential of niosomes for improving the efficacy of G. sylvestre extract as antidiabetic. Original submitted 30 March 2012; Revised submitted 29 August 2012; Published online 24 December 2012.

Oral targeting of protein kinase C receptor: promising route for diabetic retinopathy?

In patients with diabetes, hyperglycemia is known to promote high levels of diacylglycerol which activates protein kinase C (PKC) in the vascular tissues and leads to the production of vascular endothelial growth factor (VEGF) in the retina. PKC activation and increased concentration of VEGF are likely to play a key role in diabetic microvascular complications, particularly change in vascular permeability, inflammation, fluid leakage and ischemia in the retina. PKC comprises a super family of isoenzymes that is activated in response to various stimuli. The PKC family consists of 12 isomers that possess distinct differences in structure, substrate requirement, expression and localization. PKC isomer selective inhibitors and VEGF trap are likely to be new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease. A new promising therapy for diabetic retinopathy is undergoing Phase III trials, in which they proposed to target PKC ßII isomer using Ruboxistaurin by oral administration. Besides retina, PKC ßII isomer is found in higher concentration in brain, spleen, etc. So, oral targeting may be a questionable approach since generalized inhibitors may prove toxic in the treatment of diabetic retinopathy and ocular delivery may be a better alternative approach.

Solid dispersion of meloxicam: factorially designed dosage form for geriatric population.

The objective of the present work was to improve the dissolution properties of the poorly water-soluble drug meloxicam by preparing solid dispersions with hydroxyethyl cellulose (HEC), mannitol and polyethylene glycol (PEG) 4000 and to develop a dosage form for geriatric population. Differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to investigate the solid-state physical structure of the prepared solid dispersions. Higher in vitro dissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. PEG 4000 in 1: 9 drug to carrier ratio exhibited the highest drug release (100.2%), followed by mannitol (98.2%) and HEC (89.5%) in the same ratio. Meloxicam-PEG 4000 solid dispersion was formulated into suspension and optimization was carried out by 23 factorial design. Formulations containing higher levels of methyl cellulose and higher levels of either sodium citrate or Tween 80 exhibited the highest drug release.