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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and represents one of the leading causes of mortality worldwide due to multidrug-resistant TB (MDR-TB). In our work, a new formulation of biodegradable PLGA microparticles was developed for pulmonary administration of gatifloxacin, using a surface modifier agent to actively target alveolar macrophages thereby allowing to gain access of the drug to Mycobacterium tuberculosis. For this, rapid uptake of the particles by macrophages is beneficial. This process was evaluated with fluorescein-loaded microparticles using PLGA 502 or PLGA 502H as polymers and labrafil as surface modifier. Cell phagocytosis was studied in raw 264.7 mouse macrophage cell line after 3, 5, 24, and 48 h incubation with the microparticles. Labrafil enhanced the uptake rate of PLGA 502H microparticles by macrophages which was directly related to the modification of the polymer matrix. Gatifloxacin-loaded PLGA microparticles using PLGA 502 or PLGA 502H and labrafil were prepared. From our results, only microparticles prepared with PLGA 502H and labrafil exhibited high encapsulation efficiency (89.6 ± 0.2%), rapid phagocytosis by macrophages (3 h), and remained inside the cells for at least 48 h, thereby resulting in a suitable carrier to potentially treat MDR-TB.

Background: Clioquinol (CQ), a metal chelator, has gained renewed attention due to its ability to modulate metal homeostasis in neurodegenerative disorders such as Alzheimer''s disease. Purpose: To investigate the protective effects of a wide range of concentrations of CQ on two human neuroblastoma cell lines (IMR-32 and SKN-AS) and to develop and characterize a new controlled release system of CQ consisting of biodegradable microspheres. Results: H2O2 (400 μμM) adequately induced death cell in IMR-32 and SKN-AS cell lines thereby resulting in a useful model for neuroprotective studies. CQ (20--50 μμM) induced a potent and robust protective effect against peroxide-mediated oxidative stress in human neuronal-like cells (SKN-AS) determined by both MTT and flow cytometry (cell viability). These results were also confirmed by means of reactive oxygen species (ROS) production. Biodegradable poly( dl-lactic- co-glycolic acid) (PLGA) resomers assayed for microspheres preparation were PLGA-502 and PLGA-502H. Optimization by using an experimental design resulted in a formulation prepared with CQ (112 mg) and PLGA-502H (400 mg). With this formulation, mean encapsulation efficiency of 82.37% ±± 6.67% and, zero-order release rate of 58 ±± 3µµg CQ/day/10 mg microspheres between Days 10 and 35 were obtained. Conclusion: We have developed a promising formulation for the treatment of Alzheimer''s disease. [ABSTRACT FROM AUTHOR]

Aciclovir (acicloguanosine) has been demonstrated to be effective in the treatment of intraocular pathologies such as herpes simplex virus retinitis and acute retinal necrosis. Although intravitreal injections have been used with fewer side-effects than intravenous administration, the risk of complications increases with the frequency of intravitreous injections. For this reason, a biodegradable drug-delivery system, such as microspheres, able to promote prolonged release of the drug, offers a good alternative to multiple intraocular administrations. In this work, aciclovir-containing poly (D,L-lactide-co-glycolide) microspheres were prepared by the solvent evaporation method. Seven additives were incorporated in the microspheres to modulate the in vitro release rate of the drug: four non-fatty substances (polyethylene glycol 300, polyethylene glycol 1500, hidroxypropyl methylcellulose and gelatin) and three fatty substances (isopropyl myristate, vitamin E and Labrafil® M 1944 CS). Morphology of microspheres was evaluated by scanning electron microscopy. Granulometric analysis showed that particle size distribution was significantly influenced by the incorporation of additives. Loading efficiency decreased when fatty substances were added, whereas non-fatty additives promoted higher incorporation of the drug. Infrared and differential scanning calorimetry analyses indicated that microspheres prepared by the solvent evaporation process were not influenced by the type of additive used. In all cases, the initial burst resulted less than 5%. Additive-free microspheres showed a slow release within the first days, but when additives were incorporated, in general, the release rates of the drug were increased. Best release results were obtained for gelatin-containing microspheres. The release of aciclovir from these microspheres was adjusted to a zero-order kinetic from 1 to 49 days with a release constant of 1.13 µg/day/mg microspheres. A dose of 0.74 mg microspheres would be therapeutic for the herpes simplex and Epstein-Barr viruses (MIC 0.1 µg/ml) and 7.4 mg for varicella zoster virus (MIC 1 µg/ml) treatment in an animal model. [ABSTRACT FROM AUTHOR]

Abstract: Microencapsulation of rasagiline mesylate (RM) into PLGA microspheres was performed by method A (O/W emulsion) and method B (W/O/W double emulsion). The best formulation regarding process yield, encapsulation efficiency and in vitro drug release was that prepared with method A, which exhibited constant drug release for two weeks (K 0 =62.3μg/day/20mg microspheres). Exposure of SKN-AS cells to peroxide-induced oxidative stress (1mM) resulted in cell apoptosis which was significantly reduced by RM (40.7–102.5μM) as determined by cell viability, ROS production and DNA fragmentation. Daily doses of rotenone (2mg/kg) given i.p. to rats for 45 days induced neuronal and behavioral changes similar to those occurring in PD. Once an advanced stage of PD was achieved, animals received RM in saline (1mg/kg/day) or encapsulated within PLGA microspheres (amount of microspheres equivalent to 15mg/kg RM given on days 15 and 30). After 45 days RM showed a robust effect on all analytical outcomes evaluated with non-statistically significant differences found between its administration in solution or within microparticles however; with this controlled release system administration of RM could be performed every two weeks thereby making this new therapeutic system an interesting approach for the treatment of PD. [Copyright &y& Elsevier]

Abstract: The incorporation of additives such as polyoxyethylated oleic acid glycerides (PEG-derivative) can modify the release of drugs from microparticles. PEG-derivative decreases the release rate of drugs that are dissolved in PLGA matrices but if un-dissolved the initial release rate slightly increases. To clarify this behaviour the influence of adding PEG-derivative in the preparation of microspheres was investigated by scanning electron microscopy, differential scanning calorimetry, gel permeation chromatography, nuclear magnetic resonance and infrared spectroscopy. Cytotoxicity of this resulting PLGA/PEG-derivative matrix was evaluated in cell lines (fibroblasts) which are more reproducible but less specific and in primary cell cultures (splenocytes and human leucocytes) which have the advantage of their specificity. Scanning electron microscopy revealed that PLGA/PEG-derivative microspheres exhibited small surface concavities with a highly porous polymeric matrix. The incorporation of PEG-derivative caused a slight reduction in the T g values of PLGA. In vitro degradation studies showed that PEG-derivative remains within the microspheres as long as the matrix does. This PLGA/PEG-derivative matrix was well tolerated exhibiting cell viabilities similar to PLGA microspheres and can be used to modulate the release of drugs from microparticulate systems destined for parenteral administration. [Copyright &y& Elsevier]