Synthesis and colon-specific drug delivery of a poly(acrylic acid-co-acrylamide)/MBA nanosized hydrogel.
Intravenous administration of 5-fluorouracil (5-FU) for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The main objective of the present study was to develop novel oral site-specific delivery of 5-FU to the colon with less drug being released in the stomach or small intestine using biodegradable hydrogel, hydrogel nanoparticles and comparing the targeting efficiency of 5-FU to colon from both. Poly(acrylic acid-co-acrylamide) (P(AA-co-Am)) normal hydrogel and hydrogel nanoparticles (HN) were synthesized by free radical polymerization using N,N-methylene-bis-acrylamide (MBA) as cross-linker, potassium persulfate as reaction initiator and 5-FU was loaded. HN were found to be degradable in physiological medium and showed comparatively higher swelling in rat caecal medium (RCM). 5-FU entrapment was increased by increasing Am (wt%) monomer feed. In vitro release of 5-FU from normal hydrogel and HN in pH progressive medium, it was found that a AA/Am ratio of 25:75 showed higher release in RCM. The Higuchi model yielded good adjustment of in vitro release kinetics. A higher amount of 5-FU reached the colon in HN (61 +/- 2.1%) than normal hydrogel (40 +/- 3.6%) by organ biodistribution studies in albino rats.
Ray
Debajyoti
D
P.G. Department of Pharmaceutics, Sri Jayadev College of Pharmaceutical Sciences, Naharakanta, Bhubaneswar, India.
Mohapatra
Dillip K
DK
Mohapatra
Ranjit K
RK
Mohanta
Guru P
GP
Sahoo
Prafulla K
PK
D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D003106:Colon / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009928:Organ Specificity; D010316:Particle Size; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
D000178:Acrylamides; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D020100:Hydrogels; C431184:poly(acrylamide-co-acrylic acid); C021221:N,N'-methylenebisacrylamide; D005472:Fluorouracil