Co-Loaded Solid Lipid Nanocarriers of Resveratrol and Paclitaxel for Improved Bioavailability and Antitumor Efficacy in Lung Cancer Models: In Vitro and In Vivo Evaluation
نویسندگان
1 Tashkent State Medical University, Tashkent City, Uzbekistan
2 Samarkand State University named after Sharof Rashidov, Samarkand, Uzbekistan
3 Andijan State Medical Institute, Andijan, Uzbekistan
4 Bukhara State Pedagogical Institute, Bukhara, Uzbekistan
5 Central Asian Medical university, Fergana, Uzbekistan
6 Tashkent Institute of Irrigation and Agricultural Mechanization Engineers National Research University, Uzbekistan
7 Tashkent State Technical University, Uzbekistan
8 Veterinary Research Institute, Samarkand, Uzbekistan
9 Bukhara State Pedagogical Institute, Bukhara, Uzbekistan
10 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
11 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
12 Urganch Innovation University, Urgench, Uzbekistan
13 Urgench State University, Uzbekistan
doi
10.22052/JNS.2025.04.033چکیده
Lung cancer persists as a critical global health challenge, exhibiting high incidence and mortality rates. Conventional chemotherapeutics such as paclitaxel (PAC) suffer from limited aqueous solubility, dose-limiting toxicity, and resistance mechanisms that significantly compromise clinical efficacy. In this study, we engineered and evaluated solid lipid nanoparticles (SLNs) co-loaded with PAC and resveratrol (RES)—a polyphenolic antioxidant with known anticancer activity—as a novel combinatorial nanotherapeutic platform for lung cancer. The SLNs were fabricated via high-pressure homogenization using glyceryl monostearate (GMS) as the lipid core, and stabilized by Tween 80 and soy lecithin. The nanoparticles exhibited mean sizes ranging from 190.5 to 254.7 nm with narrow polydispersity indices (PDI < 0.3), and zeta potentials between –18.9 and –21.6 mV, indicative of satisfactory colloidal stability. The encapsulation efficiencies for PAC and RES exceeded 90%, ensuring robust payload retention. In vitro release kinetics followed a biphasic sustained-release profile and were best described by the Korsmeyer–Peppas model (R² = 0.9904; n = 0.46), indicating an anomalous diffusion-controlled mechanism. Cytotoxicity assays against A549 human lung carcinoma cells demonstrated enhanced antiproliferative effects for dual-loaded SLNs compared to free drugs or single-drug-loaded formulations. The IC₅₀ value for PAC–RES SLNs was significantly reduced to 2.1 µg/mL. Flow cytometric analysis revealed a substantial elevation in total apoptotic cells (\~60%) for the dual-loaded formulation. Furthermore, in vivo antitumor efficacy was validated using a BALB/c nude mouse xenograft model, where PAC–RES SLNs elicited superior tumor suppression and improved survival outcomes without inducing systemic toxicity. These findings support the potential utility of PAC–RES SLNs as a rationally designed nanomedicine for enhanced lung cancer therapy.
