Heparin, a highly sulfated glycosaminoglycan that functions as an anticoagulant drug. It is injected subcutaneously as either inpatient or outpatient. Due to pain associated with injection, and expensive in-patient fees, patients are less likely to comply with the requirements of heparin administration. This project aims to increase patient compliance by creating a targeted approach for heparin oral drug delivery. Oral drug delivery is one of the safest and painless forms of drug administration by patients. Heparin is a negatively charged drug due to its carboxyl and sulfate groups. It is a heterogeneous mixture containing sulfated monosaccharide residues of L-iduronic acid and D-glucosamine that are 1→4 linked. Therefore, it is an excellent candidate for delivery by incorporation in ionic complexed nanoparticles. These nanoparticles consist of a cationic polymer entrapping an anionic drug. The cationic polymer being used in this research project is chitosan. It is a naturally occurring amino polysaccharide with repeat units of D-glucosamine linked β-(1→4). The polymer is cationic due to the amino groups present. Chitosan is biodegradable and nontoxic, making it suitable for biomedical applications. It is beneficial for drug delivery because it is mucoadhesive, meaning it adheres to the mucosal epithelial layer of the Gastrointestinal (GI) tract. This results in enhanced penetration of large molecules, such as heparin, through the epithelial layer. In this research we are developing ionic complexed nanoparticles (ICNs) with chitosan to encapsulate heparin for use in oral drug delivery. ICNs are pH sensitive such that they can be used to release drugs based on cue within specific pH ranges. We are using this pH sensitivity by designing the heparin bound ICN’s to be stable under the acidic conditions (pH 1.5-2.0) within the stomach and for a short time in the small intestines where it will pass through the epithelial layer and release the drug at pH values about 7.2. Due to its large size, highly negative charge and high-water solubility, administration of heparin without a drug carrier results in poor absorption within GI tract. To ensure that the designed ICN heparin delivery systems can meet the strict requirements for oral drug delivery, we are studying ICN particle stability and heparin release as a function of time, pH, temperatures using simulated fluids that mimic the GI tract environment.

Ionic complexed nanoparticles for heparin drug delivery

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.