Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells

• Published in: Journal of colloid and interface science Vol. 351; no. 1; pp. 19 - 29
• Main Authors: Yallapu, Murali Mohan, Gupta, Brij K., Jaggi, Meena, Chauhan, Subhash C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-11-2010; Elsevier
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cancer; Cell Proliferation - drug effects; Chemistry; Chemotherapy; Colloidal state and disperse state; Curcumin; Curcumin - chemistry; Curcumin - pharmacology; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Screening Assays, Antitumor; Drugs; Encapsulation; Exact sciences and technology; General and physical chemistry; Humans; Intracellular drug delivery; Lactic Acid - chemistry; Lactic Acid - pharmacology; Mathematical models; Nanocomposites; Nanomaterials; Nanoparticles; Nanoparticles - chemistry; Nanostructure; Natural drug; Particle Size; Physical and chemical studies. Granulometry. Electrokinetic phenomena; PLGA nanoparticles; Polyglycolic Acid - chemistry; Polyglycolic Acid - pharmacology; Surface Properties; Sustained drug delivery; Targeted drug delivery; Tumor Cells, Cultured; Natural drug; Chemotherapy; Targeted drug delivery; Intracellular drug delivery; Curcumin; PLGA nanoparticles; Sustained drug delivery; Encapsulation; Drug; Particle size; Antibody; Nanoparticle; Alcohol; Polymer; Natural compound; Solid; Assay; Precipitation; Lysine; Formulation; Dispersed state; Electrokinetic potential; Models; Release
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2010.05.022

An optimized curcumin encapsulated PLGA nanoparticle formulation (nano-CUR6, i.e., NCUR6) enhances cellular internalization and shows improved therapeutic effects in metastatic ovarian (A2780CP) and breast (MDA-MB-231) cancer cells.
Curcumin, a natural polyphenolic compound, has shown promising chemopreventive and chemotherapeutic activities in cancer. Although phase I clinical trials have shown curcumin as a safe drug even at high doses, poor bioavailability and suboptimal pharmacokinetics largely moderated its anti-cancer activity in pre-clinical and clinical models. To improve its applicability in cancer therapy, we encapsulated curcumin in poly(lactic-
co-glycolide) (PLGA) (biodegradable polymer) nanoparticles, in the presence of poly(vinyl alcohol) and poly(L-lysine) stabilizers, using a nano-precipitation technique. These curcumin nano-formulations were characterized for particle size, zeta potential, drug encapsulation, drug compatibility and drug release. Encapsulated curcumin existed in a highly dispersed state in the PLGA core of the nanoparticles and exhibited good solid–solid compatibility. An optimized curcumin nano-formulation (nano-CUR6) has demonstrated two and sixfold increases in the cellular uptake performed in cisplatin resistant A2780CP ovarian and metastatic MDA-MB-231 breast cancer cells, respectively, compared to free curcumin. In these cells, nano-CUR6 has shown an improved anti-cancer potential in cell proliferation and clonogenic assays compared to free curcumin. This effect was correlated with enhanced apoptosis induced by the nano-CUR6 formulation. Herein, we have also shown antibody conjugation compatibility of our PLGA-NP formulation. Results of this study suggest that therapeutic efficacy of curcumin may be enhanced by such PLGA nanoparticle formulations, and furthermore tumor specific targeted delivery of curcumin is made feasible by coupling of anti-cancer antibody to the NPs.