Novel self-assembled liquid crystalline nanoparticles for transdermal delivery of Progesterone: Development, quality by design, in-vitro optimization and ex-vivo permeation studies
Salma M Mohyeldin, Mohammed M Mehanna and Nazik A Elgindy
Alexandria University, Egypt
: J Pharm Drug Deliv Res
The present chapter aimed to elaborate novel self-assembled liquid crystalline nanoparticles (LCNPs) for management of hormonal disturbances following non-invasive transdermal delivery of Progesterone. The LCNPs bearing Progesterone were prepared via a simple processing technique utilizing different glyceryl monoglycerides. Fabrication and optimization of Progesteroneloaded LCNPs were assessed via a quality by design approach based on 23 full factorial designs. The design includes the functional relationships between independent processing variables and dependent responses of particle size, polydispersity index, zeta potential, % cumulative drug release after 24 h and ex-vivo transdermal steady flux. Morphological elucidation of the prepared novel system was examined using transmission electron microscopy. The developed nanocarrier was subjected to a stability study within a period of three months at different storage temperatures. The cubic phase of LCNPs was successfully prepared using GMO (glyceryl mono oleate) via the emulsification technique. Based on the factorial design, the independent operating variables significantly affected the five dependent responses. The diameters of the prepared cubosomes were in the nano-metric range (101-386 nm) with a narrow particle size distribution, high negative zeta potential â¥-30 mV and entrapment efficiency â¥94%. The LCNPs succeeded in sustaining the drug release for almost 24 h, following a non-Fickian transport of drug diffusion mechanism. Ex-vivo study revealed a significant enhancement up to six folds in the transdermal permeation of Progesterone-loaded LCNPs compared to the aqueous drug suspension. The optimized LCNPs exhibited a high physical stability profile while retaining the cubic structure for at least three months. In conclusion, a quality by design approach successfully accomplished a predictable mathematical model permitting the development of novel LCNPs for transdermal delivery of Progesterone with the benefit of reducing its oral route hazards.