Production of letrozole-loaded alginate oxide-gelatin microgels using microfluidic systems for drug delivery applications

Abstract

Microfluidic systems are capable of producing microgels with a monodisperse size distribution and a spherical shape due to their laminar flow and superior flow. A significant challenge in producing these drug-carrying microgels is simultaneous drug loading into microgels. Various factors such as the type of polymer, the type of drug, the volume ratio of the drug to the polymer, and the geometry of the microfluidic system used to generate microgels can effectively address these challenges.The overall goal of this study was to produce mono-disperse drug-carrying microgels capable of controlled drug release. To achieve this goal, this study used a stream-focused microfluidic chip containing a coating current to prevent chip clogging. Alginate oxide was synthesized with a 30 % oxidation percentage. Alginate oxide, gelatin, and compositions of them with volume ratios of 50–50, 70–30, and 30–70, by determining their appropriate weight percentage, were used for the controlled release of letrozole. The properties of the produced microgels were measured through various tests such as drug release test, loading percentage, SEM, FTIR, swelling ratio, and dimensional stability.It was found that microgels made of a combination of alginate oxide-gelatin with volume ratios of 70–30 had a good swelling ratio and structural stability. The drug loading percentages for alginate, alginate oxide, and alginate oxide-gelatin with volume ratios of 50–50 and 30–70, respectively, were 56 %, 68 %, and 66 %, 61 % and the alginate oxide-gelatin with a volume ratio of 70–30 compared to other samples had over 70 % drug loading percentages. Furthermore, samples of alginate, alginate oxide, and alginate oxide-gelatin with volume ratios of 50–50 and 30–70 had 94 %, 63 %, 56 %, and 68 % drug release in 13 days, respectively. However, alginate oxide-gelatin with a volume ratio of 70–30 had a release rate of about 50 % in 13 days, which is a more controlled release for letrozole compared to the volume ratios of 50–50 and 30–70. Examining the drug release profile, it was concluded that drug release follows the Higuchi model and therefore follows Fick's first law of diffusion. It can be concluded that the combination of alginate oxide-gelatin produces more suitable microgels than alginate and alginate oxide for the controlled-release of letrozole. A comparison of microgels of alginate oxide and gelatin with volume ratios of 50–50 and 70–30 had better results for the cytotoxicity study compared to other samples.