PH-Sensitive Micelles Based on Star Copolymer Ad-(PCL-b-PDEAEMA-b-PPEGMA)₄ for Controlled Drug Delivery.

Huiyan Yang,Jem-Kun Chen,Jianwei Guo,Rui Tong,Chufen Yang

doi:10.3390/polym10040443

Abstract

Enhancing drug loading efficacy and stability of polymeric micelles remains a grand challenge. Here we develop adamantane-based star copolymers adamantane-[poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate)]4 (Ad-(PCL-b-PDEAEMA-b-PPEGMA)4) and their self-assembled micelles for controlled drug delivery. Results show that the polymers have excellent stability in solution with low critical micelle concentration (CMC) (0.0025–0.0034 mg/mL) and the apparent base dissociation constant (pKb) of the polymers is from 5.31 to 6.05. Dynamic light scattering analysis exhibits the great environmental response capability of the pH-sensitive micelles according to particle sizes and zeta potentials. With the synergy effect of the adamantane and hydrophobic block, the micelles display the high Doxorubicin (DOX) loading efficacy (up to 22.4%). The DOX release study shows that the micelles are capable of controlled release for drug. This work indicates the Ad-(PCL-b-PDEAEMA-b-PPEGMA)4 micelles may provide new guidelines for drug control and release system in overcoming cancer treatment.

Highlights

Cancer is a major public health problem in the world [1,2], but the diagnosis and treatment of cancer are still a challenge in the field of human biomedicine [3,4,5]
We report a novel star amphiphilic polymer adamantane-[poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate)]4 (Ad-(PCL-b-PDEAEMA-b-PPEGMA)4 ), which has a highly drug-loaded capacity and high stability of micelles featured by adamantane as the molecular core
Doxorubicin hydrochloride (DOX·HCl) which was purchased from Beijing HuaFeng United Technology Co., Ltd

Summary

Introduction

Cancer is a major public health problem in the world [1,2], but the diagnosis and treatment of cancer are still a challenge in the field of human biomedicine [3,4,5]. Owing to non-specific distribution of drugs, conventional pharmacotherapy often kills normal cells and causes toxicity to the patient [6,7,8,9]. Low concentrations of chemotherapy drugs in tumor tissue results in poor therapeutic efficacy [6,10]. Nanoparticle therapy shows unique advantages in pharmacotherapy, helping to improve the drug’s aqueous dispersity, toxicity profile, pharmacokinetic properties, as well as bioavailability. The pH of normal physiological tissue is about 7.4, the pH of extracellular solid tumors is 6.5–7.4, and the pH values of endosomes and lysosomes in tumor cells are 5.0 and. With great difference in pH between human normal cells and a tumor cells’ microenvironment, there are tremendous potential applications of a pH-responsive drug delivery system for efficient drug delivery to the tumor

Methods

Results

Conclusion