Design of lipid-polymer hybrid nanoparticles for therapy of BPH: Part I. Formulation optimization using a design of experiment approach

• Published in: Journal of drug delivery science and technology 2017-06, Vol.39, p.16-27
• Main Authors: Sengel-Turk, C. Tuba, Hascicek, Canan
• Format: Article
• Language: English
• Subjects: BPH; Factorial design; Lipid-polymer hybrid nanoparticles; Lonidamine
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2017.02.012

The primary purpose of the present research was to design a novel lipid-polymer hybrid nanoparticulate system of lonidamine based on the DoE approach for the effective treatment of benign prostatic hyperplasia. Hybrid nanoformulations were prepared through one-step self-assembly approach. The primary core material used PLGA, while DSPE-PEG-COOH and l-α-phosphatidylcholine were employed as lipid-PEG shell layer and lipid monolayer at the interface of the lipid-PEG shell and polymeric core, respectively. The molar ratios of PEG conjugated lipid to polymer and total lipids to l-α-phosphatidylcholine were determined as the investigated independent variables. Nine hybrid formulations were optimized by the application of a 32 factorial design to evaluate the major changes on the characteristics of hybrid systems such as entrapment efficiency, mean particle size and surface charge. Shape and morphology characteristics, in vitro release profiles, thermal behavior and interactions, lipid shell thickness, and storage stability were also evaluated. The important outcomes of this research revealed that the hybrid formulations prepared at the center point of the design exhibited an excellent core-shell structure, high entrapment efficiency values, and desired particle sizes. The linearity graphics and the surface response plots demonstrated significant effectiveness between the independent variables and the experimental responses. [Display omitted]