美国辛辛那提大学药学院工业药学与药剂学AdelSakr教

Type
Prodrugs Coatings
Coatings
Pectine and calcium pectinate Matrix and coatings Dextran hydrogel conjugates Prodrugs
Prof. Dr. Adel Sakr
9
Methods of Colonic Targeting
COLONIC TARGETING OF A PEPTIDE ANTI-BACTERIAL AGENT
Prof. Dr. Adel Sakr
Industrial Pharmacy Graduate Program College of Pharmacy, University of Cincinnati Cincinnati, Ohio, USA CONGRESS CHAIR, FIP-INDUSTRIAL PHARMACY SECTION
• Protection of Nisin until it reaches the colon is
essential.
Prof. Dr. Adel Sakr 7
Methods of Colonic Targeting
• Chemical/Microbiological Approach
– Bacterial count in the colon is much higher than that of the small intestine.
Prof. Dr. Adel Sakr 4
Nisin
• Active against many Gram-positive bacteria species. • Reported activity against:
– – – – – Mycobacterium Actinomyces Penicillin-resistant Neisseria gonorrhoeae Helibacter pylori Clostridium difficile Vancomycin-resistant enterococci
Dradelsakr@gmail.com
Introduction
• Nisin • Significance of colonic delivery of Nisin • Methods of colonic targeting • EUDRAGIT L30D-55 • Wurster fluid bed coating
challenge.
• Targeting drugs to the colon is becoming of great
interest for systemic absorption or local action.
Prof. Dr. Adel Sakr
3
Nisin
• Peptide antimicrobial agent • Belongs to the class of Antibiotics • Produced by Lactococcus lactis • Used as a food preservative • Consists of 34 amino acids • Solubility decreases with increasing pH • Solubility decreases in the presence of salt
• Vancomycin-resistant enterococci are a cause
for untreatable or difficult to treat bacterial infections. • Both types of organisms colonize the colon.
• Technological/Physiological Approach
– Colonic bacteria is capable of extensive enzymatic activity.
– Colonic targeting is achieved by compounds selectively degraded by the microbial enzymatic activity (prodrugs or universal systems). – Most of the materials are not approved for human use.
Fra Baidu bibliotek
Prof. Dr. Adel Sakr
6
Significance of Colonic Delivery of Nisin
• Nisin shows activity against both types of
organisms.
• Nisin will be digested in the small intestine.
Prof. Dr. Adel Sakr 8
Methods of Colonic Targeting
Delivery System
Azo-linked polyamides Azo polymers based on hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid Amylose
Prof. Dr. Adel Sakr 2
Introduction
• Peroral drug delivery is the most convenient method of
drug delivery.
• Peroral delivery of proteins and peptides presents a
Prof. Dr. Adel Sakr
5
Significance of Colonic Delivery of Nisin
• Clostridium difficile causes antibiotic associated
diarrhea leading to colitis or bowel inflammation.