Formation Mechanism, In vitro and In vivo Evaluation of Dimpled Exenatide Loaded PLGA Microparticles Prepared by Ultra-Fine Particle Processing System

Abstract

Spherical poly (D, L-lactic-co-glycolic acid) microparticles (PLGA-MPs) have long been investigated in order to achieve sustained delivery of proteins/peptides. However, the formation mechanism and release characteristics of the specific shape MPs were still unknown. This study aimed to develop a novel-dimpled exenatide-loaded PLGA-MPs (Exe-PLGA-MPs) using an ultra-fine particle processing system (UPPS) and investigate the formation mechanism and release characteristics. Exe-PLGA-MPs were prepared by UPPS and optimized based on their initial burst within the first 24 h and drug release profiles. Physicochemical properties of Exe-PLGA-MPs, including morphology, particle size, and structural integrity of Exe extracted from Exe-PLGA-MPs, were evaluated. Furthermore, pharmacokinetic studies of the optimal formulation were conducted in Sprague-Dawley (SD) rats to establish in vitro-in vivo correlations (IVIVC) of drug release. Exe-PLGA-MPs with dimpled shapes and uniform particle sizes achieved a high encapsulation efficiency (EE%, 91.50 ± 2.65%) and sustained drug release for 2 months in vitro with reduced initial burst (20.42 ± 1.64%). Moreover, the pharmacokinetic studies revealed that effective drug concentration could be maintained for 3 weeks following a single injection of dimpled Exe-PLGA-MPs with high IVIVC. Dimpled PLGA-MPs prepared using the UPPS technique could thus have great potential for sustained delivery of macromolecular proteins/peptides.

Cartilage Extracellular Matrix Scaffold With Kartogenin-Encapsulated PLGA Microspheres for Cartilage Regeneration

“…The PLGA microsphere-embedded CECM scaffold can serve to mimic some features of the native ECM; it also enables sustained and localized delivery of bioactive molecules to achieve prolonged exposure of BMSCs to bioactive molecules. Previous studies have shown that the delivery effect of PLGA is related to multiple factors ( Wu et al, 2013 ; Zhu et al, 2019 ) including the grain size of PLGA spheres; this parameter mainly affects the specific surface area, distribution of hydrophobic drugs in spheres, and polymer degradation rate ( Chen et al, 2015 ; Almeida et al, 2020 ). Therefore, it is necessary to identify a suitable particle size range that can preserve resources and effectively control KGN release.…”

Can a monthly exenatide extended release regimen provide a therapeutic and cost benefit?

“…Based on published data, the exenatide ER formulation is 100% stable in vivo for more than 3 weeks in the body (Zhu et al ., 2019). Thus, there is no justification of the weekly ER administration.…”

“…740 µg) (Cirincione & Mager, 2017). The drug is also stable, and no loss is expected due to degradation or interaction with the matrix (Cirincione & Mager, 2017; Zhu et al ., 2019).…”

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

“…In order to meet the previously discussed size range for sufficient deposition in lung airways, several methods have been developed to produce appropriate particle sizes, such as spray drying 314 , jet milling 315 and ultrasonic spray freeze drying 316 . In addition, a novel ultra-fine particle processing system (UPPS) reported by Wu's group 317 , 318 , 319 was applied as an alternative technology for microparticle preparation, due to its ability to produce microparticles under mild temperature conditions, wide range viscosity, and high encapsulation efficiency.…”