In this study, attachment and growth of Baby Hamster Kidney (BHK) cells on ethylene diamine (EDA)-plasma-treated poly(L-lactide/epsilon-caprolactone) biodegradable copolymer films were investigated. The co-polymer (Mw: 58000; Mn: 35000 and PI 1.60) was synthesised by ring-opening polymerization of the respective dimers with using stannous octoate as the catalyst. The final ratio of L-lactide to epsilon-caprolactone obtained by 1H-NMR was 87:13. The co-polymer films were treated with the EDA-plasma in a glow-discharge apparatus. The BHK-30 cell line was cultured on plain and EDA-plasma-treated films and their pre-wetted forms (with ethanol and/or cell culture medium before use). Cell attachment and growth were followed. Alkaline phosphatase (ALP) activity and glucose uptake in cell culture medium were also investigated. There was no attachment in the first 12 h. Glow-discharge treatment increased significantly the attachment and growth. Pre-wetting with ethanol and cell culture medium was also increase significantly both the attachment and growth.
The aim of the study was to determine penetration properties of Famotidine fro the formulations through colon adenocarcinoma (Caco)-2 cell monolayers and to compare in vitro with in vivo test results. It also aimed to determine the effect of particle size on the penetration properties of Famotidine when microsphere formulations were used. Famotidine was chosen as a model drug and Caco-2 cell culture model was used. Biodegradable Famotidine microspheres of poly(lactide-co-glycolide)(PLGA) polymer (50:50) were prepared by using multiple emulsion technique. Microspheres were coded according to their particle size and polymer[LHIV:60 microm Famotidine-PLGA(high viscosity), SHIV:6 microm Famotidine PLGA(high viscosity), LLIV:60 microm Famotidine-PLGA (low viscosity), SLIV:6 microm Famotidine-PLGA (low viscosity)]. Famotidine solution(5 mg/ml) and microsphere formulations were administered orally to mice and blood drug levels were determined and compared with the Caco-2 cell experiments. Permeability values of Famotidine through Caco-2 cells from various formulations were determined (log k(solution) = 7,274 +/- 0,010,log kSHIV = -3,884 +/- 0,033,log kLHIV = -2,300 +/- 0,009,log kSLIV = -4,076 +/- 0,208,log kLLIV = 3,525 +/- 0,045). Our results showed that H2 receptor antagonists alter the barrier properties of the Caco-2 cell monolayer by causing an increment in the tightness of the tight junctions. Therefore, amount of the H2 receptor antagonist-like drug at the site of action was found to be important as well as polymer type and particle size of microspheres for drug permeation. Permeation of the drug was lower when higher amounts of Famotidine were present at the diffusion site. A controlled release dosage form of H2 receptor antagonist-like drugs may be beneficial for long-term treatments.
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