Injectable In-Situ Forming Depot Based on PLGA and PLGA-PEG-PLGA for Sustained-Release of Risperidone: In Vitro Evaluation and Pharmacokinetics in Rabbits

Abstract

In the current research, novel drug delivery systems based on in situ forming gel (ISFG) (PLGA-PEG-PLGA) and in situ forming implant (ISFI) (PLGA) were developed for one-month risperidone delivery. In vitro release evaluation, pharmacokinetics, and histopathology studies of ISFI, ISFG, and Risperdal CONSTA® were compared in rabbits. Formulation containing 50% (w/w %) of PLGA-PEG-PLGA triblock revealed sustained release for about one month. Scanning electron microscopy (SEM) showed a porous structure for ISFI, while a structure with fewer pores was observed in the triblock. Cell viability in ISFG formulation in the first days was more than ISFI due to the gradual release of NMP to the release medium. Pharmacokinetic data displayed that optimal PLGA-PEG-PLGA creates a consistent serum level in vitro and in vivo through 30 days, and histopathology results revealed nearly slight to moderate pathological signs in the rabbit’s organs. The shelf life of the accelerated stability test didn’t affect the results of the release rate test and demonstrated stability in 24 months. This research confirms the better potential of the ISFG system compared with ISFI and Risperdal CONSTA®, which would increase patients’ compliance and avoid problems of further oral therapy.

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

“…Korsmeyer–Peppas tends to be more relevant to three-dimensional drug delivery systems such as peptoid-peptide hydrogels and warrants a stronger case for support. The Weibull model is associated more with nanoparticles and heterogeneous formulations; however its application in model injectable hydrogels is increasing. , According to the Korsmeyer–Peppas model (Table S6), the diffusion exponent n is slightly greater than 1 for physically encapsulated drug forms of peptoid-L-peptide ( N Phe) 4 GGGGK(AZT)Y-OH and peptoid-D-peptide ( N Phe) 4 GGGGk(AZT)y-OH and is slightly less than 1 for chemically attached drug forms. This indicates super case II transport ( n > 0.85), whereby the drug is mainly released through the erosion of the polymer matrix and/or possibly hydrolysis of the ester-drug linkage where present. , Super case II transport has been previously demonstrated for Fmoc-diphenylalanine peptide hydrogels physically encapsulated with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin .…”

“…The β values of the drug-conjugated peptoid-peptides hydrogels were calculated to be between 0.75 and 1 (( N Phe) 4 GGGGKY-OH β = 0.9550, ( N Phe) 4 GGGGk(AZT)y-OH β = 0.9748) indicating a combination of gradual drug release by diffusion (Fickian diffusion) and hydrogel erosion/polymer relaxation (case II transport) . For the drug-encapsulated peptoid-peptides hydrogels (Table S7), both ( N Phe) 4 GGGGKY-OH (β = 1.169) and ( N Phe) 4 GGGGky-OH (β = 1.088) possessed β values of >1, indicating a more complex combined drug release mechanism. , …”

Sustained Inhibition of VEGF and TNF-α Achieves Multi-Ocular Protection and Prevents Formation of Blood Vessels after Severe Ocular Trauma

“…To what extend the DDS contributes to the therapeutic outcome of TNF-α/VEGF inhibition is not clear, but PLGA-PEG-PLGA DDS has been shown to extend drug bioavailability for months [ 44 ]. When TNF-α was injected into the subconjunctival space in solution, no human IgG was detected in the eye 3 months after the injection (paper in review).…”