Naringenin (NAR), a flavonoid mainly found in citrus and grapefruits, has proven anti-cancer activities. However, the poor water solubility and low bioavailability of NAR limits its use as a therapeutic agent. The aim of this study was to develop and optimize stable naringenin nanoemulsions (NAR-NE) using a Box–Behnken experimental design to obtain a formulation with a higher efficiency. Anticancer activity of optimized NAR-NE was evaluated in A549 lung cancer cells using cell viability, flow-cytometric assays, and enzyme-linked immunosorbent assay. The stabilized nanoemulsion, which showed a spherical surface morphology, had a globule size of 85.6 ± 2.1 nm, a polydispersity index of 0.263 ± 0.02, a zeta potential of −9.6 ± 1.2 mV, and a drug content of 97.34 ± 1.3%. The NAR release from the nanoemulsion showed an initial burst release followed by a stable and controlled release for a longer period of 24 h. The nanoemulsion exhibited excellent thermodynamic and physical stability against phase separation and storage. The NAR-NE showed concentration-dependent cytotoxicity in A549 lung cancer cells, which was greater than that of free NAR. The percentage of apoptotic cells and cell cycle arrest at the G2/M and pre-G1 phases induced by NAR-NE were significantly higher than those produced by free NAR (p < 0.05). NAR-NEs were more effective than the NAR solution in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. Therefore, stabilized NAR-NE could be a suitable drug delivery system to enhance the effects of NAR in the treatment of lung cancer.

Resveratrol (RES) is a polyphenolic compound which has shown beneficial pharmacological effects such as anti-inflammatory, antioxidant, and anti-cancer effects. However, poor aqueous solubility, bioavailability, and low stability are the major limitations to the clinical application of RES. Therefore, in the present study, chitosan (CS) coated PLGA nanoparticles of RES (CS-RES-PLGA NPs) was developed, characterized and its anticancer activity was evaluated in the H1299 lung carcinoma cell line. The effects of the increase in CS coating and cryoprotectant concentration on particle size, polydispersity index (PDI) and zeta potential (ZP) were determined. The particle size, PDI, ZP and entrapment efficiency of the optimized CS-RES-PLGA NPs were found to be 341.56 ± 7.90 nm, 0.117 ± 0.01, 26.88 ± 2.69 mV and 75.13% ± 1.02% respectively. The average particle size and ZP showed a steady increase with an increase in CS concentration. The increase in positive zeta potential is evident for higher CS concentrations. The effect of trehalose as cryoprotectant on average particle size was decreased significantly (p < 0.05) when it was increased from 1%−5% w/v. TEM and SEM showed uniform particle distribution with a smooth surface and spherical shape. The CS coating provides modulation of in vitro drug release and showed a sustained release pattern. The stability of RES loaded PLGA NPs was improved by CS coating. CS-coated NPs showed greater cytotoxicity and apoptotic activities compared to free RES. The CS coated NPs had a higher antioxidant effect than the free RES. Therefore, CS coated PLGA NPs could be a potential nanocarrier of RES to improve drug solubility, entrapment, sustain release, stability and therapeutic application.

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µg/cm²/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.