PubMed · 9848439
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E Rubinstein, N Keller. 1998. Spiramycin renaissance.. https://doi.org/10.1093/jac%2F42.5.572
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CTL responses play a critical role in clearing viral infections. We have investigated the potential of poly(lactide-co-glycolide) (PLG) microparticles as an oral delivery system for peptides representing CTL epitopes from measles virus nucleoprotein. Oral administration of CTL epitopes encapsulated in 50:50 PLG microparticles, resulted in vivo priming of splenic peptide-specific CTL responses. However, the observed CTL lysis was low and cofeeding of encapsulated peptide with cholera toxin as a mucosal adjuvant did not result in any significant enhancement of the observed CTL responses. The pronounced immunostimulatory effect of microparticles, combined with their excellent tissue compatibility and biodegradability makes them a valuable delivery system for synthetic peptide immunogens. However, further work is needed to improve their efficiency via the oral route.
The objective of this study is to demonstrate the feasibility of microcapsules containing a protein and a proteinase inhibitor in order to allow the oral administration of proteic or peptidic drug. Starch/bovine serum albumin mixed-walled microcapsules were prepared using interfacial cross-linking with terephthaloyl chloride. The microcapsules were loaded with native or amino-protected aprotinin by incorporating protease inhibitors in the aqueous phase during the cross-linking process. Microcapsules can be degraded in the presence of alpha-amylase. The influence of the formulation parameters on the in vitro release of the inhibitor activity and the protein was studied. The protective effect of microcapsules with aprotinin for bovine serum albumin was revealed in vitro. The presence of the native bovine serum albumin was demonstrated after incubation of the microcapsules with aprotinin in a mixture of alpha-amylase (5.4 U/ml) and trypsin (900 spectrophotometric BAEE units/ml) for 3 h at 37 degrees C, whereas the protein was completely degraded in the release medium of the microcapsules without aprotinin.
The recently proposed Biopharmaceutics Classification System can be used to classify drugs and set standards for scale-up and post-approval changes as well as standards for in vitro/in vivo correlation for immediate and controlled release products. This classification scheme is based on determining the underlying process that is controlling the drug absorption rate and extent, namely, drug solubility and intestinal membrane permeability. Theoretical analysis and experimental results suggest that a permeability/solubility classification scheme can be used to set more rationale drug standards. In particular, high solubility/high permeability, rapidly dissolving drugs may be regulated on the basis of a single point rapid dissolution test while low solubility dissolution rate limited drugs can be regulated based on an in vitro dissolution test that reflects the in vivo dissolution process. This dissolution test may include multiple time points, media change, as well as surfactants in order to reflect the in vivo dissolution process and would be used by the manufacturer for requesting a waiver from a bioequivalence (BE) trial. For controlled release products, the regulation of bioequivalence standards is more complex due to the potential differences in position-dependent permeability/solubility and metabolism of drugs along the gastrointestinal tract. These differences may result in drug absorption rates that are highly transit time dependent. This paper will present the current status of the biopharmaceutic drug classification scheme, the underlying developed data base and its application to optimizing IR and CR products.