Development of Pectin-Type B Gelatin Polyelectrolyte Complex for Curcumin Delivery in Anticancer Therapy

Abstract

Curcumin has been proven to be a potent agent in colon cancer treatment. However, its hydrophobicity and low oral bioavailability hampered its clinical application. These limitations could be improved through appropriate formulations such as using polyelectrolyte complexes (PECs). PECs were self-assembled with polycations and polyanions in polar solvents. In this study, a novel pectin-type B gelatin PEC was developed for use in curcumin formulation. At pH 4.0, natural polyanions pectin and polycations type B gelatin spontaneously formed PECs in ethanol/water solution, whereas under mimetic gastrointestinal tract (GI tract) conditions, at pH 2.0 and 8.0, pectin and type B gelatin were electrically neutralized, and the PECs swelled to allow payload release. After being transferred to pH 7.0 condition, as in the colon environment, PECs were internalized into colon carcinomas. Thus, pectin-type B gelatin PECs were successfully prepared, and their constituent ratio and drug-loading process were also optimized. The optimum particle size of the PECs was 264.0 ± 3.1 nm and they could swell as the zeta potential was altered at either pH 2.0 or 8.0. The optimum drug content and loading efficiency were 40% and 53%, respectively. At pH 2.0, curcumin was rapidly released from curcumin-loaded PECs, whereas at pH 8.0, curcumin-loaded PECs showed a sustained-release of curcumin. The bare PECs showed very low toxicity toward human normal cells, whereas curcumin-loaded PECs, after incubation at pH 2.0 for 2 h and at pH 8.0 for 4 h, induced cell cycle arrest and exhibited cytotoxic effect to HCT116 human colon cancer cells, even though these loaded PECs were pretreated with mimetic GI tract conditions. Our pectin-type B gelatin PECs were shown to be a promising oral formulation for curcumin delivery in anticancer therapy.

Polysaccharide-Drug Conjugates: A Tool for Enhanced Cancer Therapy

“…Pectin maintains curcumin’s integrity and bioactivity and delivers it to the target site in the colon cancer cell. Pectin-type B gelatin curcumin conjugates have been more effective for curcumin delivery through oral administration in anti-cancer agents [ 100 ]. Pectin and curcumin were conjugated via the esterification reaction between carboxylic groups of pectin and phenolic –OH group of curcumin ( Figure 5 ).…”

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“…It is used for a better description of drug release behavior from a polymeric system as shown in equation 4Log (Q t /Q ∞ ) = log K kp + n log t ……… (4) Where Q t /Q ∞ = the fraction of drug release at time t, Kkp =the constant incorporating structural and geometrical features of controlled release device and (n) = a diffusional release exponent indicative of the drug release mechanism for dissolution.…”

“…Besides, curcumin in a buffer decomposes in a pH-dependent manner, and this degradation accelerates at neutral-basic conditions. Studies have suggested that curcumin could be well formulated to improve its solubility and bioavailability via a reliable controlled-or sustained-release system 4,5 .…”

Water-Insoluble, Thermostable, Crosslinked Gelatin Matrix for Soft Tissue Implant Development

“…Gelatin is a biodegradable polymer that has a protein content of 85-92%. This material is non-toxic, does not induce immunological reactions, and is generally suitable for cell adhesion and viability [11,12]. Gelatin, due to its versatile applicability, has been used for over a millennium in the food, cosmetic, and pharmaceutical industries.…”