Alginate and Chitosan-Based Delivery Systems for Improving the Bioavailability and Therapeutic Efficacy of Curcumin

Abstract

One of the major challenges in harnessing the therapeutic benefits of curcumin (an active ingredient from turmeric) is its poor bioavailability due to its short biological half-life. In this regard, nanoformulations have shown tremendous hope for improving the pharmacokinetic and therapeutic behavior of curcumin by altering its biological stability and bioavailability. Biopolymers, especially alginate and chitosan, have received special attention as excipients to prepare nanoformulations of curcumin due to their abundant availability, biocompatibility, and amicability to form different types of self-assembled structures and ease of undergoing chemical modifications. However, there are certain challenges, such as poor water solubility under physiological conditions and heterogeneity with regard to molecular weight and large-scale production of well-preserved nanostructures. Substantial advancement has been achieved towards overcoming these challenges by developing newer derivatives through a chemical modifications approach, and this has ascertained the suitability of alginate and chitosan as excipients for drug delivery systems (DDS). The present minireview briefly discusses curcumin and its limitation as a drug molecule, carbohydrates as DDS, and the recent developments related to the alginate and chitosan-based nanoformulations of curcumin. Special emphasis has been given to highlighting the impact of alginate and chitosan-based nanoformulations in improving the therapeutic efficacy and bioavailability of curcumin.

Keywords: alginate; chitosan; curcumin; drug delivery system; nano-formulation.

Figure 1

Major curcuminoids present in turmeric powder. Reproduced with permission from [3] (Food Chem. Toxicol. 2022, 166, 113254).

Figure 2

Stages of tumor progression inhibited by curcumin as the associated molecular targets are presented (↑—Upregulation, ↓—Downregulation). Reproduced with permission from [11] (Cell. Mol. Life Sci. 2008, 65, 1631–1652).

Figure 3

Chemical structure of alginate.

Figure 4

Representation of the possible interaction mechanism between curcumin and Alg Ald-Gel nanogel, postulated model of nanogel and in vitro curcumin release from Alg Ald-Gel nanogel at pH 5 and pH 7.4. The green box highlights the sites of intermolecular hydrogen bonding between the phenolic OH group in curcumin and free OH goup of Alg Ald-Gel nanogel. Reproduced with permission from [57] (Mater. Sci. Eng. C 2016, 68, 251–257).

Figure 5

The scheme shows commensal flora triggered targeted release of curcumin from alginate-curcumin micelle for ulcerative colitis treatment. Reproduced with permission from [58] (Colloids Surf. B: 2021, 203, 111756).

Figure 6

The figure shows the synthetic scheme of Cur-Alg ester, its particle size distribution, and the cleavage and release of curcumin by liver homogenate at pH 8. Reproduced with permission from [59] (J. Mol. Struct. 2023, 1283, 135307).

Figure 7

(A) Schematic illustration of the structure of bioconjugate AA-CUR and the micelle formed by conjugate AA-CUR (B) Curcumin release profile obtained for AA-CUR/oleic acid mixture at 37 °C, pH = 7.4 (C) Analysis of cytotoxicity of AA-CUR bioconjugate performed using different mouse cancer cell lines by MTT assay. * Statistical significance as compared to control (0 µg/mL of curcumin). Reproduced with permission from [60] (Eur. Polym. J. 2019, 113, 208–219).

Figure 8

Chemical structure of chitosan.

Figure 9

The images show FE-SEM image of nanoparticles prepared with chitosan: TPP ratio of 4:1 and drug release profiles of curcumin-loaded CS-NP as affected by cross-linking densities. Reproduced with permission from [74] (Pharm. Dev. Technol. 2013, 18, 591–599).

Figure 10

Schematic diagram for the nanoparticle assembly of CENP from EGF-conjugated chitosan, TPP, and curcumin. ENP—curcumin-encapsulated and EGF—conjugated chitosan/TPP nanoparticles; EGF—epidermal growth factor; TEM—transmission electron microscopy; TPP—tripolyphosphate. Reproduced with permission from [80] (Int. J. Nanomedicine 2018, 13, 903–916).