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A series of polyethylenimines-coated poly(d,l-lactide-co-glycolide)/lipid nanoparticles (PPLs) were fabricated for delivering paclitaxel via a simple nano-precipitation method. Four kinds of polyethylenimines (PEIs) (800 Da-, 2000 Da- and 25 kDa-branched PEIs, and 25 kDa-linear PEI) were selected as a polymeric coating for the nanoparticles. The PPLs were evaluated for their cytotoxic effects towards tumor cells. The nanoparticles were uniform spheres with particle sizes ranging from 135.8 to 535.9 nm and zeta potentials between 13.5 and 45.4 mV. The content of lipids and PEIs were optimized at lipids content from 0 to 40% and PEI content from 2.5% to 10%, respectively. At 20% lipid content and 5% PEI content, the formulation was found to be optimal. In vitro experiments showed that 25 kDa-branched PEI coated PLGA/lipid nanoparticles (25k-bPPLs) had higher cytotoxicity than other PPLs in several cancer cell lines. Meanwhile, 25k-bPPLs maintained high cellular delivery efficiency without excessive toxicity, which was confirmed by confocal microscopy and flow cytometry analyses. Furthermore, 25k-bPPLs displayed excellent colloidal stability in pH 7.4 PBS. In conclusion, 25k-bPPLs are promising drug delivery vehicles for cancer therapeutics.

Role of Four Different Kinds of Polyethylenimines (PEIs) in Preparation of Polymeric Lipid Nanoparticles and Their Anticancer Activity Study