*Article* **High-Payload Buccal Delivery System of Amorphous Curcumin–Chitosan Nanoparticle Complex in Hydroxypropyl Methylcellulose and Starch Films**

**Li Ming Lim and Kunn Hadinoto \***

School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore; particletechnology.ntu@gmail.com

**\*** Correspondence: kunnong@ntu.edu.sg; Tel.: +65-6514-8381

**Abstract:** Oral delivery of curcumin (CUR) has limited effectiveness due to CUR's poor systemic bioavailability caused by its first-pass metabolism and low solubility. Buccal delivery of CUR nanoparticles can address the poor bioavailability issue by virtue of avoidance of first-pass metabolism and solubility enhancement afforded by CUR nanoparticles. Buccal film delivery of drug nanoparticles, nevertheless, has been limited to low drug payload. Herein, we evaluated the feasibilities of three mucoadhesive polysaccharides, i.e., hydroxypropyl methylcellulose (HPMC), starch, and hydroxypropyl starch as buccal films of amorphous CUR–chitosan nanoplex at high CUR payload. Both HPMC and starch films could accommodate high CUR payload without adverse effects on the films' characteristics. Starch films exhibited far superior CUR release profiles at high CUR payload as the faster disintegration time of starch films lowered the precipitation propensity of the highly supersaturated CUR concentration generated by the nanoplex. Compared to unmodified starch, hydroxypropyl starch films exhibited superior CUR release, with sustained release of nearly 100% of the CUR payload in 4 h. Hydroxypropyl starch films also exhibited good payload uniformity, minimal weight/thickness variations, high folding endurance, and good long-term storage stability. The present results established hydroxypropyl starch as the suitable mucoadhesive polysaccharide for high-payload buccal film applications.

**Keywords:** curcumin; nanoparticle complex; buccal drug delivery; polysaccharides
