The oral administration of peptidic drugs requires their protection from degradation in the gastric environment and the improvement of their absorption in the intestinal tract. For these requirements, a microsystem based on cross-linked alginate as the carrier of bovine serum albumin (BSA), used as a model protein, was proposed. A spray-drying technique was applied to BSA/sodium alginate solutions to obtain spherical particles having a mean diameter less than 10 microm. The microparticles were hardened using first a solution of calcium chloride and then a solution of chitosan (CS) to obtain stable microsystems. The cross-linking process was carried out at different CS concentrations and pH values of the cross-linking medium. The CS concentration affected the BSA loading in the microparticles prepared at a pH value less than the protein isoelectric point (pI). Moreover, the BSA loading at a pH value less than the pI was higher than that at a pH similar to the pI regardless of the CS concentration. This finding could be attributable to the formation of a BSA/alginate complex. The evaluation of the interaction between BSA and alginate at different pH values by means rheological measurements confirmed this hypothesis. This approach may represent a promising way to devise a microcarrier system with appropriate size for targeting the Peyer's patches, with appropriate immobilization capacity, and suitable for the oral administration of peptidic drugs.
Our previous results demonstrated that a prodrug obtained by the conjugation of the antiretroviral drug zidovudine (AZT) with ursodeoxycholic acid (UDCA) represents a potential carrier for AZT in the central nervous system, thus possibly increasing AZT efficiency as an anti-HIV drug. Based on these results and in order to enhance AZT brain targeting, the present study focuses on solid lipid microparticles (SLMs) as a carrier system for the nasal administration of UDCA-AZT prodrug. SLMs were produced by the hot emulsion technique, using tristearin and stearic acid as lipidic carriers, whose mean diameters were 16 and 7 μm, respectively. SLMs were of spherical shape, and their prodrug loading was 0.57 ± 0.03% (w/w, tristearin based) and 1.84 ± 0.02% (w/w, stearic acid based). The tristearin SLMs were able to control the prodrug release, whereas the stearic acid SLMs induced a significant increase of the dissolution rate of the free prodrug. The free prodrug was rapidly hydrolyzed in rat liver homogenates with a half-life of 2.7 ± 0.14 min (process completed within 30 min). The tristearin SLMs markedly enhanced the stability of the prodrug (75% of the prodrug still present after 30 min), whereas the stabilization effect of the stearic acid SLMs was lower (14% of the prodrug still present after 30 min). No AZT and UDCA-AZT were detected in the rat cerebrospinal fluid (CSF) after an intravenous prodrug administration (200 μg). Conversely, the nasal administration of stearic acid based SLMs induced the uptake of the prodrug in the CSF, demonstrating the existence of a direct nose-CNS pathway. In the presence of chitosan, the CSF prodrug uptake increased six times, up to 1.5 μg/mL within 150 min after nasal administration. The loaded SLMs appear therefore as a promising nasal formulation for selective zidovudine brain uptake.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.