Berberine Encapsulated PLGA-PEG Nanoparticles Modulate PCSK-9 in HepG2 Cells

Background: The developments of new parenteral approaches to target PCSK-9 for the treatment of LDL-Cholesterol has yielded impressive results; and have shown significant decreases in the risk of mortality associated with hypercholesterolemia. However improved and convenient alternate approaches that exploit the beneficial drug target properties of PCSK-9 also need to be explored and developed. One such approach is the oral administration of Berberine using nanotechnology.

Methods: Nanoprecipitation encapsulation and physiochemical characterization of Berberine Chloride in PLGA-PEG-PLGA block copolymer has been developed and characterized in Hep-G2 cells using Berberine Chloride encapsulated nanoparticle (Bc-NP). Evaluation of PCSK-9, SREBP- 1, LDL-r, HNF-1alpha mRNAs and PCSK-9 protein expression was performed using quantitative real-time PCR (qPCR) and median fluorescence intensity (MFI) of flow cytometric studies respectively. Pearson's correlation analysis of PCSK-9 mRNA and protein levels in Berberine chloride delivery was performed.

Results: The PCSK-9 mRNA and protein expression shows a relationship to the release of Berberine from the encapsulating PLGA-PEG-PLGA polymer in a time dependent manner.

Conclusion: PCSK-9 modulation by oral administration of Berberine using nanotechnology approach can improve its pharmacokinetic profile. Further studies are needed to maximize its delivery efficiency.