ABSTRACT
In the present work, to maintain a suitable blood level of vinpocetine (VP) for a long period of time, VP-cyclodextrin-tartaric acid multicomponent complexes were prepared and formulated in hydroxypropylmethylcellulose matrix tablets. In vitro and in vivo performances of these formulations were investigated over a VP immediate release dosage form. Solubility studies were performed to evaluate the drug pH solubilization profile and to assess the effect of multicomponent complexation on VP solubility. The drug release process was investigated using United States Pharmacopeia apparatus 3 and a comparative oral pharmacokinetic study was subsequently undertaken in rabbits. Solubility studies denoted the pH-solubility dependence of VP and solubility improvement attained by complexation. Dissolution results showed controlled and almost complete release behavior of VP over a 12-h period from complex hydroxypropylmethylcellulose-based formulations. A clear difference between the pharmacokinetic patterns of VP immediate release and VP complex-based formulations was revealed. The area under the plasma concentration-time curve after oral administration of complex-based formulations was 2.1-2.9 times higher than that for VP immediate release formulation. Furthermore, significant differences found for mean residence time, elimination half-life, and elimination rate constant values corroborated prolonged release of VP from complex-based formulations. These results suggest that the oral bioavailability of VP was significantly improved by both multicomponent complexation and controlled release delivery strategies.
Subject(s)
Drug Compounding , Vinca Alkaloids/pharmacokinetics , beta-Cyclodextrins/chemistry , Administration, Oral , Animals , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Half-Life , Hydrogen-Ion Concentration , Metabolic Clearance Rate , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Molecular Weight , Rabbits , Reproducibility of Results , Solubility , Tablets , Tartrates/chemistry , Therapeutic Equivalency , Vinca Alkaloids/blood , Vinca Alkaloids/chemistry , Water/chemistryABSTRACT
Cardosin A is extracted from the pistils of the plant Cynara cardunculus L. and chitosan is a polysaccharide derived from chitin with valuable properties as a biomaterial. In this work we report our experiments on the synthesis of chitosan sponges and immobilisation of cardosin A, by entrapment. We observed that 10-15% of the incorporated cardosin A were released over 6 days of incubation. In addition, we could also note that this immobilisation procedure did not induce any specificity alterations on cardosin A. The specificity study of the enzyme, using beta-chain of oxidised insulin, showed that the immobilised and released enzymes have the same hydrolysis pattern as the free enzyme. The ability of this enzyme to hydrolyse type I collagen was maintained, after the immobilisation procedure. The biocompatibility in vivo of these sponges was evaluated by histological staining after implantation in rats submitted to abdominal surgery. Results of this study demonstrated that these chitosan sponges are very promising vehicles for the application of cardosin A, in abdominal cavity for prevention and reduction of the adhesions formation.
Subject(s)
Aspartic Acid Endopeptidases/administration & dosage , Chitosan/administration & dosage , Drug Delivery Systems , Drug Implants , Enzymes, Immobilized/administration & dosage , Plant Proteins/administration & dosage , Animals , Aspartic Acid Endopeptidases/chemistry , Biodegradation, Environmental , Collagen Type I/chemistry , Enzymes, Immobilized/chemistry , Female , Hydrolysis , Insulin/chemistry , Plant Proteins/chemistry , Rats , Rats, WistarABSTRACT
The aim of this study was to compare functional peripheral nerve recovery in the rat sciatic nerve model after reconstruction of a 10-mm gap with a biodegradable poly (DLLA-epsilon-CL) nerve guide, as filled with either fresh skeletal muscle or phosphate-buffered saline (PBS). During 24 weeks of recovery, motor and sensory functional evaluation was tested by extensor postural thrust (EPT) and withdrawal reflex latency (WRL), respectively. At the end of the experiment, anesthetized animals were prepared for motor nerve conduction velocity (MNCV) studies, followed by gastrocnemius and soleus muscle weight measurement. Motor functional recovery was greater in the muscle-grafted group, and reached a significant difference from weeks 8-12 (P < 0.05). The results of this investigation suggest that filling a nerve guide with fresh skeletal muscle induces faster maturation of regenerated nerve fibers in comparison with traditional tubular repair.
