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.

A novel vesicular transdermal delivery of nifedipine - preparation, characterization and in vitro/in-vivo evaluation.

Nifedipine is a calcium channel blocker extensively used in the treatment of anginal and hypertension. On oral administration it undergoes extensive first pass metabolism, which outweighs its absorbance through gastrointestinal tract (GIT) and bioavailability of the drug in systemic circulation. As an alternative to oral route transdermal route of drug delivery was developed. In the present investigation, proniosomes are prepared by varying the ratio of span-40, lecithin, aqueous phase and polymer. Formulation containing span-40, lecithin, isopropyl alcohol, 0.1% glycerol (5:5:4) and HPMC (2%) showed smaller vesicle size, high entrapment efficiency. The niosomal formation after hydration and their surface morphology of optimized formulation was studied by Motic and transmission electron microscopy. FTIR and differential scanning calorimetry studies were performed to unravel and understand the solid state properties of the drug and chemical interaction with formulation excipients. The ex-vivo Franz-diffusion studies were carried out in pH 6.8 using rat skin and the results showed better permeability of niosomes with good steady state flux and enhancement ratio suggesting the potential of proniosomal carriers for improved transdermal delivery of nifedipine. Skin irritation studies for 7 days, showed that the drug when formulated as proniosomes to be non-irritant with no erythemia development compared to pure drug. From the bio-distribution studies, the vesicles prepared with hydroxy propyl methyl cellulose with span-40 was found to be ideal batch as the concentration of drug at target site was higher.

Optimization of artemether-loaded NLC for intranasal delivery using central composite design.

The objective of the study was to optimize artemether-loaded nanostructured lipid carriers (ARM-NLC) for intranasal delivery using central composite design. ARM-NLC was prepared by microemulsion method with optimized formulation having particle size of 123.4 nm and zeta potential of -34.4 mV. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that drug existed in amorphous form in NLC formulation. In vitro cytotoxicity assay using SVG p12 cell line and nasal histopathological studies on sheep nasal mucosa indicated the developed formulations were non-toxic and safe for intranasal administration. In vitro release studies revealed that NLC showed sustained release up to 96 h. Ex vivo diffusion studies using sheep nasal mucosa revealed that ARM-NLC had significantly lower flux compared to drug solution (ARM-SOL). Pharmacokinetic and brain uptake studies in Wistar rats showed significantly higher drug concentration in brain in animals treated intranasally (i.n.) with ARM-NLC. Brain to blood ratios for ARM-NLC (i.n.), ARM-SOL (i.n.) and ARM-SOL (i.v.) were 2.619, 1.642 and 0.260, respectively, at 0.5 h indicating direct nose to brain transport of ARM. ARM-NLC showed highest drug targeting efficiency and drug transport percentage of 278.16 and 64.02, respectively, which indicates NLC had better brain targeting efficiency compared to drug solution.

Intranasal therapeutic strategies for management of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic and progressive age-related irreversible neurodegenerative disorder that represents 70% of all dementia with 35 million cases worldwide. Successful treatment strategies for AD have so far been limited, and present therapy is based on cholinergic replacement therapy and inhibiting glutamate excitotoxicity. In this context, role of neuroprotective drugs has generated considerable interest in management of AD. Recently, direct intranasal (IN) delivery of drug moieties to the central nervous system (CNS) has emerged as a therapeutically viable alternative to oral and parenteral routes. IN delivery bypasses the blood-brain barrier by delivering and targeting drugs to the CNS along the olfactory and trigeminal neural pathways which are in direct contact with both the environment and the CNS. In an attempt to understand how neurotherapeutics/nanoparticulate delivery systems can be transported from the nose to the CNS, the present review sets out to discuss the mechanism of transport from nose to brain. The aim of this review is to discuss and summarize the latest findings of some of the major studies on IN drug delivery in AD models, with a focus on the potential efficacy of neuroprotective treatments.

Lipid nanocarriers and molecular targets for malaria chemotherapy.

Malaria is the most serious tropical disease of humankind and a cause of much debilitation and morbidity throughout the world especially in endemic areas like India and Africa. The development of drug resistance may be due to insufficient drug concentration in presence of high parasite load. In addition, the present pharmaceutical dosage forms are ineffective thereby necessitating the development of novel dosage forms which are effective, safe and affordable to underprivileged population of the developing world. The rapid advancement of nanotechnology has raised the possibility of using lipid nanocarriers that interact within biological environment for treatment of infectious diseases. Thus, lipid based nano-delivery systems offer a platform to formulate old and toxic antimalarial drugs thereby modifying their pharmacokinetic profile, biodistribution and targetability. Further, there is a need to develop new chemotherapy based approaches for inhibiting the parasite-specific metabolic pathways. The present review highlights the advances in lipid nanocarriers and putative molecular targets for antimalarial chemotherapy.

Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment.

The objective of the study was to optimize curcumin nanoemulsion for intranasal delivery using design of experiment. Box-Behnken design was constructed using oil, surfactant and co-surfactant concentration as independent variables and their affect on response y1 (globule size) and y2 (zeta potential) were studied. The ANOVA test identified the significant factors that affected the responses. For globule size, percentage of oil, surfactant and co-surfactant were identified as significant model terms whereas for zeta potential, oil and co-surfactant were found to be significant. Critical factors affecting the responses were identified using perturbation and contour plots. The derived polynomial equation and contour graph aid in predicting the values of selected independent variables for preparation of optimum nanoemulsion with desired properties. Further, 2(4) factorial design was used to study influence of chitosan on particle size and zeta potential. The formulations were subjected to in vitro cytotoxicity using SK-N-SH cell line and nasal ciliotoxicity studies. The developed formulations did not show any toxicity and were safe for intranasal delivery for brain targeting. In vitro diffusion studies revealed that nanoemulsions had a significantly higher release compared to drug solution. Ex vivo diffusion studies were carried out using sheep nasal mucosa fixed onto Franz diffusion cells. Mucoadhesive nanoemulsion showed higher flux and permeation across sheep nasal mucosa.

Modulation of cerebral malaria by curcumin as an adjunctive therapy

Cerebral malaria is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than two million deaths annually. The current therapy is inadequate in terms of reducing mortality or post-treatment symptoms such as neurological and cognitive deficits. The pathophysiology of cerebral malaria is quite complex and offers a variety of targets which remain to be exploited for better therapeutic outcome. The present review discusses on the pathophysiology of cerebral malaria with particular emphasis on scope and promises of curcumin as an adjunctive therapy to improve survival and overcome neurological deficits.

Modulation of cerebral malaria by curcumin as an adjunctive therapy.

Cerebral malaria is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than two million deaths annually. The current therapy is inadequate in terms of reducing mortality or post-treatment symptoms such as neurological and cognitive deficits. The pathophysiology of cerebral malaria is quite complex and offers a variety of targets which remain to be exploited for better therapeutic outcome. The present review discusses on the pathophysiology of cerebral malaria with particular emphasis on scope and promises of curcumin as an adjunctive therapy to improve survival and overcome neurological deficits.

Betaxolol hydrochloride loaded chitosan nanoparticles for ocular delivery and their anti-glaucoma efficacy.

Many effective anti-glaucoma drugs available for the treatment of ocular hypertension and open angle glaucoma are associated with rapid and extensive precorneal loss caused by the drainage and high tear fluid turnover. The present study involved design of mucoadhesive nanoparticulate carrier system containing betaxolol hydrochloride for ocular delivery to improve its corneal permeability and precorneal residence time. Nanoparticles were prepared by spontaneous emulsification method and had a particle size of 168-260 nm with zeta potential of 25.2-26.4 mV. The in vitro release studies in simulated tear fluid exhibited biphasic release pattern with an initial burst followed by sustained release upto 12 h. The sterility tests confirmed that formulation was free from viable microorganisms and suitable for ocular delivery. The ocular tolerance of nanoparticles was evaluated using Hen Egg-Chorion Allantoic Membrane (HE-CAM) method and was found to be non-irritant. Stability studies of nanoparticles revealed that there was no significant change in particle size and drug content after storage at 25 ± 2°C/60 ± 5% RH over a period of 3 months. In vivo pharmacodynamic studies were carried out in dexamethasone induced glaucoma model in rabbits. The developed nanoparticles showed significant decrease in intraocular pressure (IOP) compared to marketed formulation. Optimized formulation of BN3 showed gradual reduction of IOP reaching peak value of 9.9 ± 0.5mm Hg, equivalent to 36.39 ± 1.84% reduction in IOP compared to control at the end of 5 h which was significant (p < 0.05) compared to marketed formulation. Thus, our studies demonstrate that developed nanoparticles offer a promising delivery system for the management of glaucoma.