Study of antimycobacterial, cytotoxic, and mutagenic potential of polymeric nanoparticles of copper (II) complex.

This study aimed to encapsulate and characterise a potential anti-tuberculosis copper complex (CuCl2(INH)2.H2O:I1) into polymeric nanoparticles (PNs) of polymethacrylate copolymers (Eudragit®, Eu) developed by nanoprecipitation method. NE30D, S100 and, E100 polymers were tested. The physicochemical characterisations were performed by DLS, TEM, FTIR, encapsulation efficiency and, in vitro release studies. Encapsulation of I1 in PN-NE30D, PN-E100, and PN-S100 was 26.3%, 94.5%, 22.6%, respectively. The particle size and zeta potentials were 82.3 nm and -24.5 mV for PNs-NE30D, 304.4 nm and +18.7 mV for PNs-E100, and 517.9 nm and -6.9 mV for PNs-S100, respectively. All PDIs were under 0.5. The formulations showed an I1 controlled release at alkaline pH with 29.7% from PNs-NE30D, 7.9% from PNs-E100 and, 28.1% from PNs-S100 at 1 h incubation. PNs were stable for at least 3 months. Particularly, PNs-NE30D demonstrated moderate inhibition of M. tuberculosis and low cytotoxic activity. None of the PNs induced mutagenicity.

In situ Formed Implants, Based on PLGA and Eudragit Blends, for Novel Florfenicol Controlled Release Formulations.

Drug controlled release technologies (DCRTs) represent an opportunity for designing new therapies. Main objectives are dose number optimization and secondary effects reduction to improve the level of patient/client acceptance. The present work studies DCRTs based in blended polymeric implants for single dose and long-term therapies of florfenicol (FF), a broad spectrum antibiotic. Polymers used were PLGA and Eudragit E100/S100 types. Eudragit/PLGA and FF/PLGA ratios were the main studied factors in terms of encapsulation efficiencies (EEs) and drug release profiles. In addition, morphological and physicochemical characterization were carried out. EEs were of 50-100% depending on formulation composition, and the FF releasing rate was increased or diminished when E100 or S100 were added, respectively. PLGA hydrolytic cleavage products possibly affect Eudragit solubility and matrix stability. Different mathematical models were used for better understanding and simulating release processes. Implants maintained the antimicrobial activity against Pseudomonas aeruginosa up to 12 days on agar plates. The developed DCRTs represents a suitable alternative for florfenicol long-term therapies.

An analysis of the microencapsulation of ceftiofur in chitosan particles using the spray drying technology.

Ceftiofur is a third-generation cephalosporin approved to treat numerous infections in production animals. Its commercial formulations are administered daily due to the mean life time, leading to several inconveniences, like operative challenges and non-uniform plasma levels. The objective of this work was to microencapsulate ceftiofur in chitosan particles using spray drying technology to extend the delivery and consequently reduce the dosage frequency. The effect of formulation factors on particle features was studied using a multilevel factorial design. In addition, ceftiofur thermal stability was assayed by differential scanning calorimetry and microbiological assays. Finally, a pharmacokinetic model was developed to predict theoretical plasma concentration in goats. Results showed that ceftiofur thermal stability increased after microencapsulation, indicating a protective effect of chitosan particles. Besides, MIC, IC50 and inhibition halos against E. coli and S. aureus were similar than those of the commercial product. In addition, suitable plasma levels can be theoretically maintained in goats during 48 h with a single injection. These findings suggest that chitosan microparticles could be a good vehicle for ceftiofur administration.

Design and evaluation of a recyclable intravaginal device made of ethylene vinyl acetate copolymer for bovine estrus synchronization.

In bovine estrus synchronization, intravaginal devices made of silicone are used to administer exogenous progesterone with the aim of maintain plasmatic levels above 2 ng ml-1 during the treatment. After their use, devices must be discarded. There is an important concern on the environmental impact of the disposal of these used products due mainly to the non-degradability of the silicone and to the residual content of the hormone. Different alternatives are being studied, and the use of ecological materials appears as the more important. The objective of the present contribution was to design and evaluate a recyclable intravaginal prototype using ethylene vinyl acetate copolymer (EVA). Devices were fabricated by an injection-molding technique and characterized in terms of dimensions, loading efficiency, release rate, and wing tension. An analysis was first conducted to compare three different matrices and two supports. Secondly, the best candidate prototype was assayed in both beef and dairy cattle. Finally, used matrices were recycled measuring the progesterone content in the resulting devices and testing them in vitro. According to release tests, no differences were observed between the three matrices both in vitro and in vivo. On the contrary, a better performance was achieved when a support with a more flexible Y shape was used in comparison with a rigid T geometry. Successful results were observed in non-lactating cows, with plasma concentrations above the threshold value defined for the synchronization therapy. However, lower progesterone levels resulted when devices were tested in animals with large milk production. By last, recycled matrices presented a similar initial content and in vitro release rate than original matrices. These findings could open the possibility to use recyclable EVA devices as an alternative to the non-degradable silicone intravaginal inserts. Future research must be carried out to optimize the performance of the recycled matrices in dairy cattle. Modifications of the release surface and/or the initial loading can give a solution to the lower values observed in these animals. Graphical abstract.