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

Li Ming Lim,Kunn Hadinoto

doi:10.3390/ijms22179399

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.

Highlights

The vast therapeutic activities of curcumin (CUR)—a polyphenol extracted from turmeric plants—have been well-established, where antioxidant, antimicrobial, antiinflammatory, antidiabetic, and anticancer activities of CUR have been successfully demonstrated in vivo [1,2,3]
The field emission scanning electron microscope (FESEM) image of the CUR–CHI nanoplex after lyophilization showed the appearance of agglomerates of the nanoplex exhibiting roughly spherical shapes with individual sizes in the range of
The results showed that the addition of polyvinyl alcohol (PVA) and AGN resulted in lower CUR entrapment efficiency from roughly 81–82% in their absence to 57–63% in their presence

Summary

Introduction

The vast therapeutic activities of curcumin (CUR)—a polyphenol extracted from turmeric plants—have been well-established, where antioxidant, antimicrobial, antiinflammatory, antidiabetic, and anticancer activities of CUR have been successfully demonstrated in vivo [1,2,3]. Numerous human clinical trials on the use of CUR in the management of several chronic diseases (e.g., cardiovascular, metabolic, neurological, cancers) have shown promising results [4,5]. The oral route, produces low CUR systemic bioavailability due to CUR’s low solubility in the gastrointestinal fluid, and due to CUR degradation by first pass metabolism [7,8]. High CUR dosages near its toxicity limit are often needed in clinical trials to achieve the intended therapeutic outcomes [9]

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Conclusion