| Management of illness through medication is about to enter an era of rapid growth in the area of Pharmaceuticals that are of peptide research have created a wide variety of biomedical peptide hormones, synthetic peptide, enzyme substrates and inhibitors. Although they are highly potent and specific in their physiological function, most of them are usually not therapeutically active by oral administration. In fact, they have an extremely short biological half-life when administered parenterally and repeated injections are often needed. These compounds require parallel development of viable delivery systems to improve their systemic bioavailability and to overcome the drawbacks associated with parenteral administration.A synthetic pentapeptide, thymopentin, representing thebiologically active aminoacid sequence 32-36 of thymopoietin, wasfound to posses the immunomodulating activity of thymopoietinitself (i.e. ability to induce T-cell differentiation andmaturation and to affect the immunoregulatory balance) ; thus it wasconsidered to represent the active site of thymopoietin . Nanoparticle has been regarded as a useful vector for targeted drug delivering system in recent years for they can protect drugfrom being degraded and can cross the gastrointestinal barrier todeliver their drug content in blood, lymph or even target organ. Many people paid attention to the nanoparticles formed of biodegradable materials, such as poly-lactide (PLA), polylactide-co-polycolide (PLGA) and alkylcyanoacrylate (ACA), et al.Chitosan is the deacetylated chitin and ha.1 transmucosal absorption enhancement. However, in neutral and basic environments, the chitosan molecules will lose their charge, rendering it unsuitable for use as an absorption enhancer. N-trimethyl chitosan(TMC), which has the superior water solubility, especially at neutral and basic pH values, acts in a similar way as chitosan by opening tight junctions to allow for the paracellular transport of these compounds.In this study, N-trimethyl chitosan was synthesized and then was used to prepare Tp5 loaded N-trimethyl chitosan nanoparticle (Tp5-TMC~NP) by ionotropic gelation of the cationic polysaccharide TMC with sodium alginate. By using HPLC method, various factors influencing the particle size and entrapment ratio, such as the concentration of TMC, the concentration of sodium alginate, the concentration of Tp5, pH value, the composite of mixed solution, the adding velocity of sodium alginate and the stirring velocity in the nanoparticle forming process were investigated to optimize the preparation method. The resulting Tp5-TMC~NP had regular spherical surface and a narrow particle size with a mean diameter of 110.6 nm. The average entrapment efficiency was 78.8%.The Tp5~TMC-NP ly^philized formulation was investigated by taking morphology and reconstitution as indexes. The stability experiment indicated that the lyophilized Tp5-TMC~NP was stablewithout obvious changes in morphology, particle size, pH, entrapment ratio in 4 °C or -20 °C after storage of 3 months. The in vitro drug release experiment indicated that lyophilized Tp5~TMC-NP powder in vitro could be characterized by Weibull equation. - **?Pharmacodynamics study in vivo was executed by giving the Tp5-TMC-NP periodically and orally to rats, which were injected immunosuppressant (Cyclophosphamide, CTX) three days before the administration. Seven days later, we verified the CD4+/CD8+ in the blood by flow cytometer and found oral Tp5~TMC-NP and injected Tp5 had similar affectionOur study shows that new material N-trimethyl chitosan as vector in oral drug delivery system is feasible. It has special prospect in the administration peptide and protein orally.
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