Comparison of site-dependent degradation of peptide drugs within the gut of rats and rabbits

Abstract

Intestinal luminal degradation of neurotensin and acetylneurotensin-(8-13) within the gut of rats and rabbits was compared using brush-border membranes. Patterns of differential proteolysis of these two peptides within the intestine were similar within the same species and between the species. In both rats and rabbits, jejunal brush-border membranes had the highest proteolytic activities degrading neurotensin and acetylneurotensin-(8-13), and caecal or ileocaecal brush-border membranes had the lowest activities. In both species, patterns of site-dependent degradation of neurotensin and acetylneurotensin-(8-13) agreed with the distribution profiles of endopeptidase-24.11 and angiotensin-converting enzyme within the gut. The distal intestine of rats and rabbits has the lowest activities degrading these two compounds. The results demonstrate that distribution of peptidases within the gut will affect site-dependent degradation and absorption of peptide drugs.

Formulation and evaluation of chitosan microspheres of aceclofenac for colon‐targeted drug delivery

“…In simulated intestinal fluid (SIF), the highest SR of 0.8270.93 was observed for ACM 4 and the lowest SR of 0.3770.22 for ACM 16 . The increased polymer concentration led to an increase in SR from ACM 1 to ACM 4 (0.42 to 0.86 in SIF), whereas an increase in cross-linker yielded to a decrease in SR for formulation from ACM 13 to ACM 16 (0.67 to 0.36 in SIF).…”

“…In SCF (control) the least polymer ratio in ACM 1 (1:1) released about 58.770.57% and the highest drug to polymer ratio in ACM 4 (1:3) led to a drug release of about 23.570.47% up to 24 h. In SCF (enzyme) the least polymer concentration (ACM 1 ) led to 10271.52% of cumulative percentage drug release at 6 h and the batch ACM 4 released 10271.50% at the end of 24 h. The ACM 3 batch which was formulated with a drug to polymer ratio of 1:3, released 10571.43% at the end of 16 h was selected as an optimised batch. The cumulative % drug release of formulation (ACM 1 to ACM 4 ) in pH 7.4 with rat caecal content is given in Figure 3a.…”

“…The long colonic residence time provides an opportunity for the absorption of drugs [2]. Furthermore, the colon is considered as an important site for the administration of peptide drugs to avoid degradation by peptidases present in the stomach and to reduce the hydrolytic enzyme activity in the small intestine [3,4]. For proper site specific delivery to the colon, dosage forms have been prepared from [5], or coated with [6], selected polysaccharides to achieve this aim.…”

Gellan Film as an Implant for Insulin Delivery

“…In contrast to the small molecular weight drugs, proteins are high molecular weight polypeptides that are susceptible to proteolysis and denaturation under conditions such as high temperature, extreme pH and organic solvents [1]. The oral route, the traditional and most widely used method of drug administration, is not feasible for protein drugs because they are easily degraded by the acidic environment in the stomach and proteolytic enzymes in the small intestine [2]. In addition, due to the large molecular size of proteins, the gastrointestinal wall acts as a diffusion barrier for their effective absorption [3].…”

Biodegradable Polymers for Protein and Peptide Drug Delivery

“…Bioavailability via this route is poor for molecules of molecular mass greater than several hundred daltons. In addition, proteins are susceptible to hydrolysis and modification at gastric pH levels and can be degraded by proteolytic enzymes in the small intestine (3). Parenteral delivery of proteins and peptides has been the method of choice for systemic delivery due to ease of administration, the avoidance of biological barriers through which it is difficult for proteins to pass, and the ability to achieve pharmacologic levels of circulating protein over a relatively short period of time.…”