Solid lipid nanoparticles and nanostructured lipid carriers in oral cancer drug delivery

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 × 106 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®). 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.

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

Marrubiin-loaded solid lipid nanoparticles' impact on TNF-α treated umbilical vein endothelial cells: A study for cardioprotective effect.

Polyphenols such as curcumin (Cur) and resveratrol (Res) have been recently shown to have potential to inhibit proliferation of highly aggressive melanoma cells. This study was designed to investigate the feasibility of a topical delivery system, using a solid lipid nanoparticles (SLNs) loaded delivery systems, that can enhance the skin penetration and anti-cancer efficacy of combination of these polyphenols. Negatively charged Cur-Res SLNs with a mean diameter of 180.2 ± 7.7 nm were prepared using high shear homogenization method. Cur-Res SLNs were found to be stable up to 2 weeks under 4°C. The in vitro release study showed that Res was released five time more than curcumin. The permeability of resveratrol was about 1.67 times that of curcumin from the SLN-gel formulation which was significantly (p < 0.05) lower than from SLN suspension. More than 70% of Cur-Res SLNs were bound to skin locally in a skin binding study suggesting potentially utility of Cur-Res SLNs in the treatment of localized melanoma. In fact, the electrical cell-substrate impedance sensing (ECIS) measurements suggested that Cur-Res combination has potential to stop cell migration of B16F10 melanoma cells. Furthermore, both, Cur-Res SLNs and Cur-Res solution at the ratio of 3:1 demonstrated a strong synergistic inhibition of SK-MEL-28 melanoma cell proliferation. Further evaluation of Cur-Res SLNs in vivo melanoma models are warranted to establish the clinical utility of Cur-Res formulations in melanoma therapy.

Novel Curcumin-Resveratrol Solid Nanoparticles Synergistically Inhibit Proliferation of Melanoma Cells

Forced degradation study is the degradation of new drug substances and drug products in more severe conditions than accelerated conditions. Forced degradation study were conducted to demonstrate the specificity of stability-indicating methods, providing insight into degradation pathways and drug degradation products, assisting in the elucidation of degradation product structures, identifying degradation products that could be spontaneously generated during storage and use of drugs and to facilitate improvement in manufacturing process and formulation corresponding with accelerated stability studies. Statins, a class of lipid-lowering medications, are the most widely prescribed drugs and an example of an unstable drug. Statins are susceptible to hydrolysis in the presence of high temperatures and humidity. Therefore, the review discusses various studies of forced degradation studies in six statins drug (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) to describe the drug's intrinsic stability thus it can assist the selection of formulations and packaging as well as proper storage conditions.

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Forced degradation study of statins: a review

Objective : Solid lipid nanoparticles (SLNs) of Curcuminoids were formulated and characterized in order to improve poor oral bioavailability of Curcumin. In vivo pharmacokinetics study in rats was conducted to demonstrate improved oral bioavailability. Methods : High pressure homogenization followed by ultrasonication method was adopted to formulate solid lipid nanoparticles of Curcumin. Compritol 888 ATO and Precirol ATO 5 were explored as solid lipids with LIPOID S 75 being used as surfactant. Freeze dried solid lipid nanoparticles were compared with marketed formulation of Curcumin (Adcumin®) in rat plasma using High Pressure Liquid Chromatography (HPLC) method using ultraviolet (UV) detector. Results : Particle size measurements performed on Solid lipid nanoparticles of Curcumin revealed the mean particle size of 200-300 nm for optimized formulations and entrapment efficiency of close to 80%. Sucrose and Dextrose were suitable cryoprotectants to prepare freeze dried solid lipid nanoparticles. Curcumin loaded solid lipid nanoparticles exhibited sustained release pattern during in vitro release kinetics. Conclusion : In vivo pharmacokinetics study in Swiss albino rats revealed that encapsulation of Curcumin into solid lipid nanoparticles increased oral bioavailability of Curcumin to 12 folds when compared with marketed formulation of Raw Curcumin (Adcumin®).

Formulation of curcuminoid loaded solid lipid nanoparticles in order to improve oral bioavailability

Objective: Simvastatin, a HMG-CoA reductase inhibitor widely used in the treatment of Hyper (dys) lipidemia causes myotoxicity and hepatotoxicity. These safety issues limit dose of Simvastatin, lead to additional monitoring of the patients as well as discontinuation of therapy. To alleviate the adverse effects and to improve efficacy and safety profile, Simvastatin was encapsulated in the nanoparticulate formulation and compared with marketed reference formulation (Zocor tablets). Methods: The nano particles (NPs) were prepared using single emulsion diffusion method and optimized for particle size, PDI, zeta potential, encapsulation efficiency. Results: The efficacy and safety of final formulation were evaluated in HFD induced hyperlipidemic albino rats. The results suggested that the NPs have significant improvement of efficacy and reduction of the toxicity in comparison to marketed reference formulation. Conclusion: By encapsulating the Simvastatin in the NPs, the 50% dose reduction can be achieved without compromising efficacy. Keywords: Nanoparticles, Simvastatin, Dose reduction, HFD model, Myopathy, HMG CoA

Improvement of efficacy and safety profile of simvastatin in comparison to reference product (zocor tablets) using nanoparticulate formulation approach

Deepak G. Gupta

Papers

Formulation of curcuminoid loaded solid lipid nanoparticles in order to improve oral bioavailability

Improvement of efficacy and safety profile of simvastatin in comparison to reference product (zocor tablets) using nanoparticulate formulation approach