Hydrocaffeic acid-chitosan coating of gastric patch provides long-acting mucoadhesive delivery of model chemotherapeutic agent

The development of a long-acting orally administered dosage form is a challenge. Here, we report development of a multi-layered mucoadhesive gastric patch that could deliver entrapped chemotherapeutic agent for eight days after oral administration. The multi-layered patch was designed to contain core layer, mucoadhesive layer and backing layer. The core layer contained the model chemotherapeutic agent, regorafenib. The mucoadhesive layer made of chitosan-hydrocaffeic acid conjugate showed greatest mucoadhesion strength of 18.1 +/- 0.78 kPa in freshly excised rat gastric mucosa. The backing layer made of hydrophobic polycaprolactone-polydimethylsiloxane composite showed the contact angle of 120 +/- 4.7 degrees after placement of water drop. The entrapped regorafenib predominantly released from the mucoadhesive-side of the patch into simulated gastric fluid and showed a zero-order release profile. The patches were found to be stable for desired characteristics for up to 3 months in long term storage conditions. The pharmacokinetic studies in rat model revealed constant plasma concentration of regorafenib sustained for 8 days after oral administration of gastric patch. The gastric tissue where the patch adhered for 8 days did not show any significant histological changes compared with the normal gastric tissue. The oral administration of single dose of regorafenib-loaded gastric patch in FaDu cell xenografted tumor bearing athymic nude mice has shown significant (P < 0.05) reduction in the tumor volume over 7 days compared to the control group. Taken together, the multi-layered mucoadhesive gastric patch can be developed as a long-acting oral drug delivery system.

Automated summary

We developed a multi-layered mucoadhesive gastric patch that can deliver chemotherapeutic agent continuously for 8 days after oral administration. The patch consists of a core layer containing the drug, a mucoadhesive layer made of chitosan-hydrocaffeic acid conjugate, and a backing layer made of hydrophobic polycaprolactone-polydimethylsiloxane composite. The patch showed sustained release of the drug in simulated gastric fluid and remained stable during long-term storage. In animal studies, the patch provided constant plasma concentration of the drug for 8 days and did not cause significant histological changes in the gastric tissue. The patch also demonstrated significant reduction in tumor volume in a mouse model. Therefore, the multi-layered mucoadhesive gastric patch has potential as a long-acting oral drug delivery system.