Fabrication of Sustained Release Curcumin-Loaded Solid Lipid Nanoparticles (Cur-SLNs) as a Potential Drug Delivery System for the Treatment of Lung Cancer: Optimization of Formulation and In Vitro Biological Evaluation

Abstract

The goal of current research was to develop a new form of effective drug, curcumin-loaded solid lipid nanoparticles (Cur-SLNs) and test its efficacy in the treatment of lung cancer. Different batches of SLNs were prepared by the emulsification-ultrasonication method. For the optimization of formulation, each batch was evaluated for particle size, polydispersity index (PI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). The formulation components and process parameters largely affected the quality of SLNs. The SLNs obtained with particle size, 114.9 ± 1.36 nm; PI, 0.112 ± 0.005; ZP, -32.3 ± 0.30 mV; EE, 69.74 ± 2.03%, and DL, 0.81 ± 0.04% was designated as an optimized formulation. The formulation was freeze-dried to remove excess water to improve the physical stability. Freeze-dried Cur-SLNs showed 99.32% of drug release and demonstrated a burst effect trailed by sustained release up to 120 h periods. The erythrocyte toxicity study of Cur-SLNs and its components demonstrated moderate hemolytic potential towards red blood cells (RBCs). The cytotoxic potential of the formulation and plain curcumin was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against A549 cell line. After 48 h of incubation, Cur-SLNs demonstrated more cytotoxicity (IC₅₀ = 26.12 ± 1.24 µM) than plain curcumin (IC₅₀ = 35.12 ± 2.33 µM). Moreover, the cellular uptake of curcumin was found to be significantly higher from Cur-SLNs (682.08 ± 6.33 ng/µg) compared to plain curcumin (162.4 ± 4.2 ng/µg). Additionally, the optimized formulation was found to be stable over the period of 90 days of storage. Hence, curcumin-loaded SLNs can be prepared using the proposed cost effective method, and can be utilized as an effective drug delivery system for the treatment of lung cancer, provided in vivo studies warrant a similar outcome.

Keywords: cellular uptake; curcumin; cytotoxicity; erythrocyte toxicity; lung cancer; solid lipid nanoparticle; solubility.

Figure 1

Schematic representation for the preparation of curcumin loaded solid lipid nanoparticles (Cur-SLNs).

Figure 2

(A) Particle size (114.9 nm) of optimized formulation measured by Malvern Zetasizer 4 (Malvern Instruments). (B) TEM photograph of Cur-SLNs showing spherical shape and smooth surface.

Figure 3

Cumulative % release of curcumin from Cur-SLNs in PBS (0.01 M, pH 7.4) and plain curcumin. Initial burst effect followed by sustained release effect up to 120 h.

Figure 4

% hemolysis caused by Cur-SLNs, plain curcumin, formulation components (lipid: GMS, surfactant: tween 80, cryoprotectant: trehalose).

Figure 5

% Viability of curcumin and Cur-SLNs treated A549 cells for 24 h. IC₅₀ value of Cur-SLNs and plain curcumin are 26.12 ± 1.24 µM and 26.12 ± 1.24 µM, respectively.

Figure 6

Stability of plain curcumin and Cur-SLNs in PBS (pH 7.4) at 37 °C. Data as mean ± SD, n = 3.