Application of Design of Expert software for evaluating the influence of formulation variables on the encapsulation efficacy, drug content and particle size of PEO-PPO-PEO/Poly(DL-lactide-co-caprolactone) nanoparticles as carriers for SN-38

Abstract

Background and aims. Hydrophobic substances are mainly encapsulated into polymer nanocarriers in order to improve their solubility, enable their administration, at the same time to empower targeted tissue or cell specific delivery of the drug using the encapsulating vehicle as targeting and controlled release platform. 7-Ethyl-10-hydroxycamptothecin (SN-38) is an active metabolite of Irinotecan, showing 100- fold to 1000-fold higher effect than Irinotecan, but its clinical use is limited because of its extreme hydrophobicity, as it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents.
 Method. In order to fully exploit the potential of the nanoprecipitation as a method for preparation of Poly(DL-lactide-co-caprolactone)- poly(ethylene oxide) - poly(propylene oxide) - poly(ethylene oxide) (P(DL)LCL/PEO-PPO-PEO) nanoparticles and evaluate the influence of the polymer P(DL)LCL, stabilizing agent PEO-PPO-PEO copolymer (Lutrol F127) and the drug concentration (SN-38) upon drug entrapment efficiency, size and drug content, a D-optimal experimental design for response surface using Design Expert Version 9.0.4.1. software investigation was created and statistically analyzed.
 Results. We have observed that at higher SN-38 concentration during the preparation procedure (nanoprecipitation, solvent diffusion method), and due to its extremely low water solubility, the drug will start to precipitate as unprotected crystals at a faster pace compared to polymer aggregation, leading to extremely low encapsulation efficacy and waste of the active compound. The most desirable combination of factor settings are SN-38=0.5 mg, Polymer=5mg and F127=4%.
 Conclusion. This investigation utilizes the design of experiment approach and extends the primary understanding of impact of formulation development of P(DL)LCL/PEO-PPO-PEO nanoparticles as carriers for SN-38.

Development and Characterization of New Miconazole-Based Microemulsions for Buccal Delivery by Implementing a Full Factorial Design Modeling

“…Over the first initial configuration of the model with linear regression with no transformation, the Box–Cox plot helped in diagnosing inadequacies of the statistical model by proposing a square root transformation. Koliqi R. et al used this algorithm to obtain an improved predictive model for studying the entrapment efficiency and drug content in the development of polymeric nanoparticles [ 120 ]. The transformation approach is helpful in the experimental design when it is wisely applied to control the response variance [ 121 , 122 ].…”