In situforming poly(lactic acid-co-glycolic acid) implants containing leuprolide acetate/β-cyclodextrin complexes: preparation, characterization, andin vitrodrug release

Abstract

In situ forming implants (ISIs) based on poly(lactic acid-co-glycolic acid) (PLGA) containing leuprolide acetate/β-cyclodextrin (LA/β-CD) complexes were prepared.Incorporation of LA or complexes did not change T g values of ISIs (48.4-49.6 °C). ISIs containing complexes with more β-CD content showed higher surface and bulk porosity.Higher β-CD portion in complexes improved solvent release, decreased initial burst release and facilitated diffusion out of drug for corresponding ISIs. Complexation of LA with β-CD (1/10, w/w) significantly improved its stability within PLGA matrix before release (total LA release of 91.3%). ISIs did not show any cellular cytotoxic effects against L929 fibroblast cells.

Optimization and in Vitro Evaluation of Injectable Sustained-Release of Levothyroxine Using PLGA-PEG-PLGA

“…10. Rahimi et al evaluated the cytotoxicity effects of ISFI formulation on fibroblast cells after 24 h and reported cell viability values from 89 to 100% [39]. The cell viability of the ISFG 50% (96.17 ± 1.15%) was higher than that of the ISFG 30% (86.37 ± 0.76), ISFG 40% (90.27 ± 2.01), and ISFI (91.70 ± 2.17%) as shown in Fig.…”

“…A mixture of double-distilled water (59.5% v/v), acetonitrile (40% v/v), phosphoric acid (0.5% v/v) (isocratic) with a flow rate of 1.2 mL/min was used as eluent. The NMP was also detected in the release medium at 220 nm with double-distilled water (68% v/v) containing trifluoroacetic acid (0.1% v/v) and acetonitrile (32% v/v) (isocratic) as eluent with a flow rate 0.5 mL/min [38,39].…”

“…for each group was prepared and incubated for 24 h. Then, a sterile membrane (pore size 0.22 μm) was employed to filter 2 mL of this solution, and subsequently, 20 μL of the filtered solution was directly added into the center of each well and incubated for 24 h. Then, the culture medium was discarded, and the cell viability % was determined by adding 500 μL of MTT solution (0.5 mg/mL in PBS). After 4 h, 100 μL of DMSO was replaced with the culture medium, then the plate was agitated for 1 h. Finally, the absorbance was measured by a microplate reader (VMax®, Canada) at 570 nm (sample) and a reference wavelength was set up at 630 nm [39].…”

“…For any subcutaneously administered formulation, it is vital to investigate its side effects on the skin [50]. To this end, the biocompatibility projections of ISFI formulation including their cytotoxic effects were carried out via mouse L929 cell line (fibroblast cells) that has been initiated from adipose tissue with fibroblast morphology [11,39]. The cell viability after 24 h was investigated by employing MTT assay [51] and the results were shown in Fig.…”

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

“…In vitro NMP release was evaluated via quantifying the total of NMP that was released from the formulations into the release media by HPLC at λ 220 nm, C18 column (Brisa LC2, 4.6 × 250 mm, 5 µm), injection volume 20 µL, and flow rate 0.6 mL/min at room temperature. An isocratic mixture of trifluoroacetic acid (0.1% v/v) (68% v/v) and acetonitrile (32% v/v) was used as eluent with a flow rate of 0.5 mL/min as mobile phase [28,29].…”