Research PaperA new solubility enhancement strategy of capsaicin in the form of high-payload submicron capsaicin-chitosan colloidal complex

- CAP submicroplex is easily prepared by ambient mixing of CAP and CHI solutions.
- Structural integrity of CAP submicroplex is governed by concentration, pH, RCHI/CAP.
- CAP submicroplex is efficiently prepared at ≈85% CAP usage rate with ≈75% payload.
- Partially amorphous CAP submicroplex produces prolonged high apparent solubility.
- CAP submicroplex has similar antimicrobial activity as the native CAP.

Clinical application of capsaicin - a major component of chili peppers known for its numerous therapeutic activities - faces the hurdle of poor oral bioavailability due to its low aqueous solubility. While capsaicin nanocapsules have been extensively investigated as a bioavailability enhancement strategy, their low payload limits their effectiveness. Herein we developed a new bioavailability enhancement strategy of capsaicin in the form of high-payload submicron capsaicin-chitosan colloidal particle complex (or submicroplex in short) prepared by electrostatically driven self-assembly complexation between capsaicin and chitosan. The effects of preparation conditions (i.e. capsaicin concentration, chitosan/capsaicin ratio, and pH) on the (a) structural integrity of the capsaicin submicroplex upon centrifugation and freeze drying, (b) physical characteristics (i.e. size, zeta potential, payload, colloidal stability), and (c) preparation efficiency were investigated, from which the optimal preparation conditions were determined. The optimal formulation exhibited (1) high payload (≈75%), (2) high colloidal stability, and (3) good solubility enhancement capability attributed to its partially amorphous form, resulting in high apparent solubility that was maintained for 6 h at 5 × of the thermodynamic solubility. Lastly, the complexation with chitosan did not have any adverse effect on the antimicrobial activity of capsaicin, hence signifying the preservation of capsaicin's bioactivities in the submicroplex.

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