53 Synthesis of a novel protein-friendly amphiphilic material and its application in protein drug delivery

Abstract

Objectives We synthesized an environmentally friendly amphiphilic material PK3-PEI with good mechanical properties, pH sensitivity and biocompatibility, aiming at improving the acidic microenvironment produced by the degradation of polyester compounds and poor mechanical properties of PK3. PK3-PEI spontaneously forms micelles in pH 7.4 PBS and rapidly degrades into non-toxic small molecules in acidic conditions. Surface PEI with large positive charges effectively promotes cell targeting and accelerates the release of drug after entering the cells. Methods PK3 and PEI were linked using a connection molecule. Activation of –OH groups on PK3 (0.46 g) was accomplished using HMDI (50-fold) in chloroform at 80°C for 4 hours. The intermediate was precipitated with diethyl ether and incubated with PEI (Mw 2000 kDa, linear, 0.46 g) in chloroform at 80°C for 4 hours. PK3-PEI was collected through repeated precipitation in diethyl ether. For the preparation of PK3-PEI micelles, 100 μL of BSA solution (40 mg/mL) and 40 mg of PK3-PEI were dispersed in chloroform in dialysis bags. The PK3-PEI micelles were obtained by dialysis against pH 7.4 PBS. Results The connection ratio of PK3 and PEI was 1:1. The particle size and ζ potential of micelles were 50.3 nm and 25.7 mV, respectively.The in vitro release profile showed PK3-PEI had a shorter hydrolysis cycle and higher pH sensitivity than PK3. The MTT assay showed blank PK3-PEI micelles had lower cytotoxicity (4.6%) than free PEI (18.7%). Cellular uptake indicated PK3-PEI micelles had higher uptake efficiency than PK3 (p? Conclusions PK3-PEI micelles have a better degradation curve and targeting effect for the delivery of antitumor drugs and can be used as a promising carrier in cancer treatment.