Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels

Abstract

Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery.

Photopolymerized Thermosensitive Poly(HPMAlactate)-PEG-Based Hydrogels: Effect of Network Design on Mechanical Properties, Degradation, and Release Behavior

“…This evidence did not confirm the trend observed in nonphotopolymerized hydrogels, where polymers of shorter PEG length yielded a stronger hydrogel. 40 Hydrogels having shorter PEG length are expected to have higher G′ for two reasons. First, because at equal weight percentage of the polymer, the molar concentration of M 20 P 4 , having the smallest molecular weight, is higher as compared to the molar concentration of M 20 P 10 and M 20 P 20 .…”

Two-component thermosensitive hydrogels: Phase separation affecting rheological behavior

“…FITC-BSA and NR were chosen to stain hydrophilic and hydrophobic domains, respectively [21,33]. Subsequently 100 µl of each polymer mixture l of each polymer mixture was dispensed in duplo in a 96-well plate and incubated at 37 °C for 1h.…”

“…PEG end-capped with aliphatic blocks [32] and PEG flanked by pHPMAlac outer blocks [21,33], aqueous phase separation has been described in simple binary systems (one type of polymer in water), at certain conditions of polymer concentration and temperature. In this case, phase separation is attributed to the formation of polymer-rich regions composed of highly "packed" and interconnected polymeric clusters (flower-like micelles), and water-rich regions mainly composed of free micelles and hydrated single polymeric chains [34].…”

FRAP in Pharmaceutical Research: Practical Guidelines and Applications in Drug Delivery

“…FRAP showed that the release rate of bovine serum albumin (BSA) depended on the protein size and the hydrogel molecular weight between the cross-links. In related work, FRAP was used to measure the diffusion of dextrans in the same type of hydrogel for different temperatures used during thermogelling (53). The diffusion and mobile fractions were found to decrease upon elevating the temperature above 25° C, and the mobility could be adjusted by changing the PEG block length.…”