Temperature-Responsive Biocompatible Copolymers Incorporating Hyperbranched Polyglycerols for Adjustable Functionality

Abstract

Temperature-triggered copolymers are proposed for a number of bio-applications but there is no ideal material platform, especially for injectable drug delivery. Options are needed for degradable biomaterials that not only respond to temperature but also easily accommodate linkage of active molecules. A first step toward realizing this goal is the design and synthesis of the novel materials reported herein. A multifunctional macromer, methacrylated hyperbranched polyglycerol (HPG-MA) with an average of one acrylate unit per copolymer, was synthesized and copolymerized with N-isopropylacrylamide (NIPAAm), hydroxyethyl methacrylate-polylactide (HEMAPLA) and acrylic acid (AAc). The potential to fully exploit the copolymers by modification of the multiple HPG hydroxyl groups will not be discussed here. Instead, this report focuses on the thermoresponsive, biocompatible, and degradation properties of the material. Poly(NIPAAm-co-HEMAPLA-co-AAc-co-HPG-MA) displayed increasing lower critical solution temperatures (LCST) as the HPG content increased over a range of macromer ratios. For the copolymer with the maximum HPG incorporation (17%), the LCST was ~30 °C. In addition, this sample showed no toxicity when human uterine fibroid cells were co-cultured with the copolymer for up to 72 h. This copolymer lost approximately 92% of its mass after 17 hours at 37 °C. Thus, the reported biomaterials offer attractive properties for the design of drug delivery systems where orthogonally triggered mechanisms of therapeutic release in relatively short time periods would be attractive.

Poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)-graph-polydopamine as a Thermoresponsive Surface with Adjustable Transformation Temperature for Efficient Microalgal Cell Adhesion and Detachment

“…32 Generally, the temperature of the maximum endothermic peak of the thermoresponsive polymer is regarded as its LCST. 33 This is because the temperature which corresponds to the maximum endothermic peak of the polymer is close to the temperature of turbidity onset for the polymer solutions obtained from the turbidity measurements. 34 However, the thermal sensitivity of cross-linked polymers is stronger, resulting in a sharp change in the turbidity for the polymers undergoing the onset temperature of the endothermic transition.…”

“…This is attributed to the rapid dehydration of the copolymers when the temperature crosses a certain point (LCST), resulting in an obvious thermal effect when the external temperature is above the LCST . Generally, the temperature of the maximum endothermic peak of the thermoresponsive polymer is regarded as its LCST . This is because the temperature which corresponds to the maximum endothermic peak of the polymer is close to the temperature of turbidity onset for the polymer solutions obtained from the turbidity measurements .…”

Linear and nonlinear rheology of liberase-treated breast cancer tumors

“…The random tetrameric copolymer LQG was prepared via benzoyl peroxide-initiated free radical copolymerization of individual monomers N-isopropylacrylamide (NIPAM, 83%), 2-hydroxyethyl methacrylate conjugated to poly(lactic acid) (HEMA-PLA, 7%), acrylic acid (AAc, 1%), and methacrylated hyperbranched polyglycerol (HPG-MA, 9%) as previously reported. 37,44 Monomer structures are provided in Fig. S1.…”

In Situ Drug Delivery to Breast Cancer-Associated Extracellular Matrix

“…Similarly, the proteolysis of HA into a lower molecular weight species (LWM-HA) has been correlated with lymph node metastasis, shortened survival, and breast cancer treatment resistance. ,,− Whether the production of HA into LMW-HA requires precise cellular processing or if exogenous hyaluronidase would produce LMW-HA (and similarly stimulate breast cancer metastasis) has not been tested in vivo. However, with the recent advancement of ECM-degrading methods in early clinical trials , coupled with the advent of biomaterials that can deliver therapeutics directly to the tumor site, − there is both an opportunity and a critical need for focused investigations to thoroughly define the relationship between the degradation of tumor ECM and tumor progression.…”