Fabrication of Gelatin Microgels by a “Cast” Strategy for Controlled Drug Release

Abstract

In this paper, we propose a “casting” strategy to prepare intrinsically fluorescent, uniform and porous gelatin microgels with multi‐responsiveness. Gelatin microgels with tunable size were obtained by copying the structure of a porous CaCO3 template. The diameter of the gelatin microgels was sensitive to salt concentration and pH. Doxorubicin and Rhodamine B as model drugs were loaded into the microgels via electrostatic interaction and release of the payload was triggered by changing the salt concentration and pH, respectively. Cell experiments demonstrated that the gelatin microgels had an excellent biocompatibility and biodegradability. The merits of gelatin microgels such as tunable size, biocompatibility, and stimulus responsive upload and release of positively charged small molecules will permit the microgels as excellent carriers for drug delivery. The whole manufacturing process is furthermore environmental‐friendly involving no organic solvents and surfactants.

Growth factor sequestration and enzyme-mediated release from genipin-crosslinked gelatin microspheres

“…However, due to the consumption of primary amines during crosslinking and the addition of negatively charged genipin [20], both gel types in the current experiment have been altered to possess a negative net charge for attracting cationic growth factors. Other studies have reported similar zeta potentials of gelatin carriers ranging from −9 mV [16] to −13 mV [46] at physiological pH.…”

“…After the initial burst-release of unbound growth factor, spontaneous release due to gradual diffusion, in the absence of degradation, was also found to be minimal with both GelA and GelB carriers. Other factors such as temperature [8], and solution ion concentration [8,46], pH [46], and may affect the conformation of the gelatin carrier or electrochemical affinity with loaded proteins. Microspheres were loaded overnight at 37 °C to maximize molecular mobility, optimizing swelling and growth factor uptake [8].…”

“…Microspheres were loaded overnight at 37 °C to maximize molecular mobility, optimizing swelling and growth factor uptake [8]. Loading was carried out in an aqueous environment (PBS) at physiological pH to maximize hydrogel swelling as a result of chain repulsion from high charge density from ionized carboxyl groups [46] which also attract and bind cationic growth factors. In this way, release experiments were designed to harness and optimize the factors affecting binding and release of growth factors from gelatin microsphere carriers based on the outcomes of previously published studies, resulting in an effective and efficient electrochemically-selective gelatin hydrogel delivery system.…”

Silk microgels formed by proteolytic enzyme activity

“…Microgels are microscopic hydrogel particles with tunable biological, chemical and mechanical properties [1, 2]. Natural structural biomaterials such as bone, horn, nail, skin, feather and hair are structures of self-assembled protein molecules [3].…”

Water-binding of protein particles

“…Genipin and transglutaminase (Tgase) were used to increase the crosslink density. Genipin is a crosslinker that has been used previously in combination with, for example, chitosan [26] [184] and the proteins gelatin; [26] [174] bovine serum albumin; [26] β-lactoglobulin; [121] and casein. [136] Crosslinking of proteins by genipin follows a two-step reaction with the primary amino groups of the proteins, resulting in a blue colour.…”