1 research outputs found
Preparation of PGA–PAE-Micelles for Enhanced Antitumor Efficacy of Cisplatin
Poly-γ-l-glutamic acid (PGA) is an outstanding drug carrier candidate
owning to its excellent biodegradability and biocompatibility. The
PGA carrier may shield toxic drugs from the body and enable the delivery
of poorly soluble or unstable drugs and thereby minimize the side
effects and improve drug efficacy. However, the limitation of PGA
as a drug carrier is low drug loading efficiency (DLE), which is usually
below 30%. In this study, we reported a chemical modification method
using l-phenylalanine ethyl ester (PAE). PGA–PAE construct
was amphiphilic, which could form micelles in aqueous solution. Cisplatin
(CDDP), a commonly used chemotherapy drug whose side effect is well-known,
was used as a model molecule to test the drug-loading efficiency of
PGA–PAE. In this paper, two sizes of CDDP-loaded PGA–PAE
micelles (MÂ(Pt)-1 and MÂ(Pt)-2) were prepared, the average diameter
of MÂ(Pt)-1 was 106 ± 6 nm and MÂ(Pt)-2 was 210 ± 9 nm. The
DLE of MÂ(Pt)-1 and MÂ(Pt)-2 was 52.8 ± 2.2 and 55.8 ± 1.2%,
respectively. Both exhibited excellent biocompatibility, stability,
and drug-retaining capability in physiological condition. The in vitro
accumulative drug-releasing profile, IC<sub>50</sub> for different
tumor cell lines HeLa, A549, and HCCC9810, and in vivo pharmacokinetics
were similar between these two micelles; however, MÂ(Pt)-1 showed higher
tumor tissue retention and longer efficient cancer cell internalization
time (up to 20 d). Our results suggested PGA–PAE micelle carriers
reduced the toxicity of CDDP and its size at around 100 nm was the
better for CDDP high-efficacy