Fabrication, Optimization, and Evaluation of Paclitaxel and Curcumin Coloaded PLGA Nanoparticles for Improved Antitumor Activity

Abstract

Codelivery of chemotherapeutic drugs in nanoparticles can enhance the therapeutic effects against tumors. However, their anticancer properties and physiochemical characteristics can be severely influenced by many formulation parameters during the preparation process. It is a complicated development phase to select the optimal parameters for preparation of nanoparticles based on the commonly used one single parameter method, which consumes a lot of money, time, and effort, and sometimes even fails. Therefore, the statistical analysis based on Box−Behnken design (BBD) has attracted much attention in bioengineering fields because it can illustrate the influence of parameters, build mathematical models, and predict the optimal combinational factors in a decreased number of experiments. In this study, we used a three-factor three-level BBD design to optimize the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles coloaded with two anticancer drugs curcumin and paclitaxel (PLGA-CUR-PTX nanoparticles). The surfactant concentration, polymer concentration, and oil−water ratio were selected as independent variables. An optimized model of the formulation for PLGA-CUR-PTX nanoparticles was validated. The optimal nanoparticles possessed a uniform spherical shape, with an average size of 99.94 nm, and the drug encapsulation efficiencies of CUR and PTX were 63.53 and 80.64%, respectively. The drug release from nanoparticles showed a biphasic release behavior, with a release mechanism via diffusion and fundamentally quasi-Fickian diffusion. The optimized nanoparticles demonstrated an enhanced cytotoxicity effect with lower IC 50 values to 4T1 and MCF-7 breast cancer cell lines compared to free drugs. In summary, BBD optimization of CUR and PTX coloaded nanoparticles yielded a favorable drug carrier that holds potential as an alternative treatment for anticancer therapy.

Selection and Control of Process Conditions Enable the Preparation of Curcumin-Loaded Poly(lactic-co-glycolic acid) Nanoparticles of Superior Performance

“…7 Thus, this effort adds to those aiming to overcome some limitations hitherto experienced by the single emulsion technique. 28,32,33 By gathering these findings, the results obtained via single emulsion may become more competitive and closer to those obtained using other encapsulation procedures.…”

“…Still, the single emulsion remains advantageous as it achieves high concentrations of NPs as well as by enabling a more practical circularization of the process: since the organic solvent used is not required to be partially miscible in water, its reuse is easier . Thus, this effort adds to those aiming to overcome some limitations hitherto experienced by the single emulsion technique. ,, By gathering these findings, the results obtained via single emulsion may become more competitive and closer to those obtained using other encapsulation procedures.…”

“…Thus, the nanoformulation based on PLGA NPs to CUR delivery has proven to increase its absorption in the organism and protect it from degrading agents, in addition to allowing the design of versatile DDS for different applications. In this sense, formulations comprising CUR-loaded PLGA NPs have recently promoted: ( i ) increase in bone regeneration in implanted areas in type-2 diabetic mice; ( ii ) decrease in the Aβ plaques aggregation, which is directly associated to inflammatory processes of the Alzheimer’s disease; ( iii ) anti-COVID-19 activities; ( iv ) anticancer activities against some of the most dangerous types of tumors, such as liver, brain, and chemoresistant breast cancer; − ( v ) anti-atherosclerotic activity; and ( vi ) reversal of corticosteroid resistance in smokers …”

“…The studies on this subject have mainly addressed factors such as use of co-stabilizers, concentration of components ( i.e. , amount of solvent, surfactants, polymers or copolymers, and CUR), different combinations of solvents, different lactide/glycolide ratios of PLGA; and speed of agitation, dropping rate or sonication power, according to the encapsulation method used. ,− Moreover, considering the sensitivity of CUR, other factors, such as pH, temperature, and light exposure, may individually or combined affect its preservation during the encapsulation process. Consequently, different parameters of the CUR-loaded NPs, such as the encapsulation efficiency (EE), drug release, and ultimately the NP performance, can also be affected.…”

Codelivery of Phytochemicals with Conventional Anticancer Drugs in Form of Nanocarriers

“…It was found that PNPs of doxorubicin and betanin reduced the cell sustainability amount of MCF-7 cells in breast cancer more than doxorubicin and betanin alone [ 113 ]. Hu H. et al delivered paclitaxel and curcumin using PLGA nanoparticles and was found that optimized formulation provided improved cytotoxicity, having reduced IC 50 in MCF-7 cells of breast cancer compared to free drugs [ 114 ].…”