Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness

Abstract

Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-Myc, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 10 6 times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN R). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.

The effects of curcumin as dietary supplement for patients with polycystic ovary syndrome: An updated systematic review and meta‐analysis of randomized clinical trials

“…Despite trying to overcome that by additives and pharmacological combinations, investigations of these new formulas versus standard CUR are still not well researched (Lopresti, 2018). However, new nanoparticles showed positive results (Gupta et al, 2020). CUR has an antihyperlipidemic effect through its antioxidant effect and regulation of lipid metabolic genes (Zingg, Hasan, & Meydani, 2013).…”

Skin cancer therapeutics: nano-drug delivery vectors—present and beyond

“…The authors reported 69.78 folds and 9 folds higher oral bioavailability as compared to free Curcumin and marketed formulation (CurcuWIN ® ). The results ensure the efficacy of Curcumin solid lipid nanoparticles in treating cancer and other inflammatory diseases [77] The nanometric size and complexity of colloidal populations are one of the reasons why polymorphic transitions have not been deciphered precisely. However advanced biophysical techniques such as cryo-and freeze-fracture transmission electron microscopy, SAXS, and SANS are being applied to study SLN structures.…”

Nanoantioxidants: Pioneer Types, Advantages, Limitations, and Future Insights

“…Several studies have shown that some antioxidants, such as lycopene [215], quercetin [216], curcumin [217], and astaxanthin [218] can be successfully loaded onto NLCs. Other studies revealed the successful encapsulation of resveratrol [219], idebenone [220], ferulic acid [221], and curcumin [222] on SLNs. Some of the most common techniques applied for the synthesis of SLNs and NLCs are presented in Figure 9 [209].…”