orabase and Parkinson-Disease

Nanosized dioscin-loaded zein-CMC (DZC) complex comprising dioscin (glycoside saponin), zein (corn protein), and carboxymethyl cellulose (CMC) is fabricated through anti-solvent coprecipitation. The optimized ratio of zein to CMC for the homogenous complexation is 5:1, and DZC maintains its stability in a wide range of pH (3.0-8.0) and ionic strength (0-50 mm NaCl). No biological toxicity of DZC is found in Caenorhabditis elegans with a normal lifespan and body size. Parkinson's disease (PD) is characterized by the loss of dopamine (DA) and dopaminergic neurons. In cat-2 mutant with defective biosynthesis of DA, DZC-fed animals show intact DA behaviors including basal slowing response (≈60%) and alcohol avoidance (≈80%). Such DA promotional effects are a result of the enhanced expression/activation of DA transporter, DAT-1 in DA neurons. Taken together, DZC has a potential for preventing PD as an oral-administered drugs and supplements.

Topics: Animals; Caenorhabditis elegans; Carboxymethylcellulose Sodium; Diosgenin; Disease Models, Animal; Parkinson Disease; Zein

This study focused on developing a gastroretentive drug delivery system employing a triple-mechanism interpolyelectrolyte complex (IPEC) matrix comprising high density, swelling, and bioadhesiveness for the enhanced site-specific zero-order delivery of levodopa in Parkinson's disease. An IPEC was synthesized and directly compressed into a levodopa-loaded matrix employing pharmaceutical technology and evaluated with respect to its physicochemical and physicomechanical properties and in vitro drug release. The IPEC-based matrix displayed superior mechanical properties in terms of matrix hardness (34-39 N/mm) and matrix resilience (44-47%) when different normality's of solvent and blending ratios were employed. Fourier transform infrared spectroscopy confirmed the formation of the IPEC. The formulations exhibited pH and density dependence with desirable gastro-adhesion with Peak Force of Adhesion ranging between 0.15 and 0.21 N/mm, densities from 1.43 to 1.54 g/cm(3) and swellability values of 177-234%. The IPEC-based gastroretentive matrix was capable of providing site-specific levodopa release with zero-order kinetics corroborated by detailed mathematical and molecular modeling studies. Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery.

Topics: Adhesiveness; Animals; Antiparkinson Agents; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Galactans; Gastric Mucosa; Hardness; Humans; Hydrogen-Ion Concentration; Kinetics; Levodopa; Mannans; Methacrylates; Models, Chemical; Models, Molecular; Molecular Conformation; Parkinson Disease; Plant Gums; Polymers; Solubility; Solvents; Spectroscopy, Fourier Transform Infrared; Swine; Technology, Pharmaceutical

The effect of repeated electroconvulsive shock (ECS) and L-dopa on contralateral head-turning induced by electrical stimulation of the caudate nucleus in rats was determined. Repeated ECS treatment consisting of a single daily ECS for 10 days was found to increase the number of caudate stimuli required to induce head-turning. As reported by others, oral L-dopa (250 mg/kg) was also found to antagonize the caudate stimulation-induced head-turning. The repeated ECS treatment had an additive effect with the 250 mg/kg L-dopa dose to increase the number of stimulations to induce the head-turn. These findings support previous reports that repeated ECS enhances dopamine-mediated behaviors as well as the theory that caudate stimulation-induced head-turning is mediated in part by dopaminergic mechanisms.

Topics: Animals; Carboxymethylcellulose Sodium; Caudate Nucleus; Electric Stimulation; Electroshock; Head; Levodopa; Male; Movement; Parkinson Disease; Rats; Rats, Inbred Strains