Oxytetracycline versus Doxycycline Collagen Sponges Designed as Potential Carrier Supports in Biomedical Applications

Many research studies are directed toward developing safe and efficient collagen-based biomaterials as carriers for drug delivery systems. This article presents a comparative study of the properties of new collagen sponges prepared and characterized by different methods intended for biomedical applications. The structural integrity is one of the main properties for a biomaterial in order for it to be easily removed from the treated area. Thus, the effect of combining a natural polymer such as collagen with an antimicrobial drug such as oxytetracycline or doxycycline and glutaraldehyde as the chemical cross-linking agent influences the cross-linking degree of the material, which is in direct relation to its resistance to collagenase digestion, the drug kinetic release profile, and in vitro biocompatibility. The enzymatic degradation results identified oxytetracycline as the best inhibitor of collagenase when the collagen sponge was cross-linked with 0.5% glutaraldehyde. The drug release kinetics revealed an extended release of the antibiotic for oxytetracycline-loaded collagen sponges compared with doxycycline-loaded collagen sponges. Considering the behavior of differently prepared sponges, the collagen sponge with oxytetracycline and 0.5% glutaraldehyde could represent a viable polymeric support for the prevention/treatment of infections at the application site, favoring tissue regeneration.

Waterborne poly(urethane-urea)s films as a sustained release system for ketoconazole

Ketoconazole (KTZ) was incorporated in waterborne poly(urethane-urea)s dispersions (WPUU), aiming at the production of films for drug sustained release. Dispersions based on poly(ethylene glycol-block-propylene glycol) (PEG-b-PPG) (four monomers with different contents of PEG hydrophilic segments), poly(propylene glycol), isophorone diisocyanate, dime-thylolpropionic acid and hydrazine were produced and characterized by apparent viscosity and average particle size (APS). Cast films-drug interaction was investigated by Fourier-Transform infrared spectrometry (FTIR). In vitro dissolution assays were performed in simulated gastrointestinal juices, followed by application of kinetic models. Stable pseudoplastic dispersions, with APS between 27 to 320 nm were obtained. FTIR from KTZ-loaded films indicated interactions between polymer and drug. In vitro release of KTZ was achieved above 80%, notably influenced by PEG-based segments content up to 2 h, followed by sustained release for 8 h. Higuchi’s and first-order equations described the drug kinetic profile, as diffusion of the drug and erosion of the swollen polymer, respectively.

Metal-Organic Framework MIL-53(Fe) as an Adsorbent for Ibuprofen Drug Removal from Aqueous Solutions: Response Surface Modeling and Optimization

Ibuprofen contamination from water sources has been increasingly alarming due to its environmentally accumulative retention; however, the strategies for ibuprofen-containing water treatment are still an enormous challenge. Herein, we described the utilization of metal-organic frameworks MIL-53(Fe) (MIL = Materials of Institute Lavoisier) for the adsorption of ibuprofen in synthetic solution. Firstly, the MIL-53(Fe) was solvothemally synthesized and then characterized using the X-ray diffraction and Fourier-transform infrared spectroscopy techniques. The optimization of ibuprofen adsorption over MIL-53(Fe) was performed with three independent variables including ibuprofen concentration (1.6–18.4 mg/L), adsorbent dosage (0.16–1.84 g/L), and pH (2.6–9.4) according to the experimental design from response surface methodology. Under the optimized conditions, more than 80% of ibuprofen could be eliminated from water, indicating the promising potential of the MIL-53(Fe) material for treatment of this drug. Kinetic and isotherm models also were used to elucidate the chemisorption and monolayer behavior mechanisms of ibuprofen over MIL-53(Fe).

An analytical study of drug release kinetics from a degradable polymeric matrix

In modern days, biodegradable polymeric matrix used as the kingpin of local drug delivery system is in the center of attention. This work is concentrated on the formulation of mathematical model elucidating degradation of drug-loaded polymeric matrix followed by drug release to the adjacent biological tissues. Polymeric degradation is penciled with mass conservation equations. Drug release phenomenon is modeled by considering solubilization dynamics of drug particles, diffusion of the solubilized drug through polymeric matrix along with reversible dissociation/recrystallization process. In the tissue phase, reversible dissociation/association along with internalization processes of drug are taken into account. For this, a two-phase spatio-temporal model is postulated, which has ensued to a system of partial differential equations. They are solved analytically with appropriate choice of initial, interface and boundary conditions. In order to reflect the potency of the advocated model, the simulated results are analogized with corresponding experimental data and found laudable agreement so as to validate the applicability of the model considered. This model seems to foster the delicacy of the mantle enacted by important drug kinetic parameters such as diffusion coefficients, mass transfer coefficients, particle binding and internalization parameters, which is illustrated through local sensitivity analysis.

Intracellular and Plasma Trough Concentration and Pharmacogenetics of Telaprevir

PURPOSE: Triple therapy for HCV-1 infection consists in boceprevir or telaprevir, ribavirin and PEG-interferon. Telaprevir is a P-glycoprotein substrate and it is metabolized by CYP3A4/5. No data have been published on intracellular penetration of telaprevir. We determined peripheral blood mononuclear cells (PBMCs) and trough plasma S and R telaprevir isomers concentrations; moreover, we evaluated the influence of some single nucleotide polymorphisms (SNPs) on these pharmacokinetic data after 1 month of triple therapy in humans. METHODS: Plasma and intracellular telaprevir concentrations were determined at the end of dosing interval (Ctrough) using ULPC-MS/MS validated methods; allelic discrimination was performed through real-time PCR. RESULTS: Median telaprevir Ctrough plasma concentrations were 2579 ng/mL and 2233 ng/mL for the pharmacologically more active S, and R, enantiomers, respectively, with median S/R plasma ratio of 1.11. In PBMC, the medians were 6863 ng/mL and 1096 ng/mL for S and R, respectively, with median S/R being 5.73. The PBMC:plasma ratio for S was 2.59 for R. Plasma ribavirin concentrations were directly correlated with plasma S-telaprevir concentrations. In linear regression analysis, only CYP24A1_rs2585428 SNP (p=0.003) and body mass index (p=0.038) were able to predict S-telaprevir PBMC concentrations. CONCLUSIONS: Our preliminary data could increase the understanding of mechanisms underlying telaprevir intracellular and plasma exposure, suggesting the implementation of pharmacogenetics in these drug kinetic studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.