PLGA from PolySciTech used in fundamental research on in-situ forming implant drug release kinetics.

One method of delivering drug in a controlled release manner is to load the drug into a biocompatible, water-miscible organic solvent (n-methylpyrrolidinone) along with degradable PLGA. After this solution is injected into a patient the solvent exchanges with the water inside the patient to solidify the PLGA around the drug trapping it until it can be released. This method is used in the popular Atrigel® delivery system which is currently used in clinical products such as sublocade (extended release buprenorphine for addiction therapy). Despite these developments, several factors behind the exact driving mechanisms and controlling factors of in-situ forming gels and their release kinetics still remain to be elucidated. Recently, researchers at Purdue University used PLGA (AP041) from PolySciTech (www.polyscitech.com) to generate a series of in-situ forming implants containing model drug fluorescein. They then carefully tracked the drug release kinetics using a novel MRI methodology to understand the driving factors of release. This research holds promise to improve the development of in-situ implants for drug delivery. Read more: Hopkins, Kelsey A., Nicole Vike, Xin Li, Jacqueline Kennedy, Emma Simmons, Joseph Rispoli, and Luis Solorio. "Noninvasive characterization of In Situ forming implant diffusivity using diffusion-weighted MRI." Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919304067

“Highlights: In situ forming implants (ISFIs) are injectable, long-acting drug release depots. Diffusion-weighted MRI was used as a novel modality to noninvasively analyze ISFIs. DWI can quantify spatial-temporal changes in diffusivity within ISFIs in situ. DWI gives insight into transport properties within ISFIs both in vitro and in vivo. Abstract: In situ forming implants (ISFIs) form a solid drug-eluting depot, releasing drug for an extended period of time after a minimally-invasive injection. Clinical use of ISFIs has been limited because many factors affect drug release kinetics. The aim of this study was to use diffusion-weighted MRI (DWI) to noninvasively quantify spatial-temporal changes in implant diffusivity in situ. ISFIs were formed using poly(lactic-co-glycolic) acid, with a molecular weight of either 15 kDa or 52 kDa, and fluorescein as the mock drug. Drug release, polymer erosion and degradation, and implant diffusivity were analyzed in vitro over 21 days. DWI was also performed in vivo over 5 days. Spatial diffusivity maps of the implant were generated using DWI data. Results showed constant diffusivity at the implant shell ((1.17 ± 0.128) × 10−3 mm2/s) and increasing diffusivity within the interior over time (from (0.268 ± 0.0813) × 10−3 mm2/s during day 1 to (1.88 ± 0.0400) × 10−3 mm2/s at 14 d), which correlated with increasing porosity of the implant microstructure. Implants formed in vivo followed the same diffusivity trend as those in vitro. This study validates the use of DWI to provide novel functional information about implant behavior through its ability to noninvasively characterize transport properties within the implant both in vitro and in vivo. Keywords: in situ forming implants Controlled release Drug delivery MRI Diffusion-weighted imaging Diffusivity.”

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