Study on colon-specific 5-Fu pH-enzyme Di-dependent chitosan microspheres

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Biomedical Engineering

Background:

• Colon-specific drug delivery systems (CDDS) are crucial for improving oral drug bioavailability.
• Chitosan-based systems offer potential for targeted delivery due to their biocompatibility and mucoadhesive properties.

Purpose of the Study:

• To develop and evaluate novel pH-enzyme Di-dependent chitosan microspheres (MS) for colon-specific delivery of 5-Fluorouracil (5-Fu).
• To optimize formulation parameters and assess the in vitro and in vivo performance of the developed CDDS.

Main Methods:

• Microspheres were prepared using emulsification/chemical cross-linking and coating techniques.
• Formulation variables (polymer concentration, drug-polymer ratio, crosslinking agent, stirring speed) were optimized using orthogonal design.
• In vitro drug release studies simulated gastrointestinal transit.
• In vivo pharmacokinetic studies were conducted in rats comparing chitosan MS with 5-Fu solution.

Main Results:

• Optimized chitosan MS demonstrated controlled particle size and high encapsulation efficiency.
• In vitro studies showed minimal drug release in simulated stomach and intestinal conditions.
• In vivo studies in rats revealed sustained plasma 5-Fu concentrations after oral administration of the chitosan MS.
• In vitro release profiles correlated well with in vivo pharmacokinetic data.

Conclusions:

• The developed pH-enzyme Di-dependent chitosan MS is a promising system for colon-specific drug delivery of 5-Fu.
• This formulation enhances oral bioavailability and provides sustained drug release, improving therapeutic outcomes.