Guanylyl cyclase activation reverses resistive breathing–induced lung injury and inflammation

Inspiratory resistive breathing (RB), encountered in obstructive lung diseases, induces lung injury. The soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is down-regulated in chronic and acute animal models of RB, such as asthma, chronic obstructive pulmonary disease, and in endotoxin-induced acute lung injury. Our objectives were to: (1) characterize the effects of increased concurrent inspiratory and expiratory resistance in mice via tracheal banding; and (2) investigate the contribution of the sGC/cGMP pathway in RB-induced lung injury. Anesthetized C57BL/6 mice underwent RB achieved by restricting tracheal surface area to 50% (tracheal banding). RB for 24 hours resulted in increased bronchoalveolar lavage fluid cellularity and protein content, marked leukocyte infiltration in the lungs, and perturbed respiratory mechanics (increased tissue resistance and elasticity, shifted static pressure–volume curve right and downwards, decreased static compliance), consistent with the presence of acute lung injury. RB down-regulated sGC expression in the lung. All manifestations of lung injury caused by RB were exacerbated by the administration of the sGC inhibitor, 1H-[1,2,4]oxodiazolo[4,3-]quinoxalin-l-one, or when RB was performed using sGCα1 knockout mice. Conversely, restoration of sGC signaling by prior administration of the sGC activator BAY 58-2667 (Bayer, Leverkusen, Germany) prevented RB-induced lung injury. Strikingly, direct pharmacological activation of sGC with BAY 58-2667 24 hours after RB reversed, within 6 hours, the established lung injury. These findings raise the possibility that pharmacological targeting of the sGC–cGMP axis could be used to ameliorate lung dysfunction in obstructive lung diseases

Mucoadhesive in situ gel formulations of miconazole nitrate for the treatment of mucosal candidiasis

This study focused on developing in situ gel formulations of miconazole nitrate with poloxamer 188 and 407 for treatment of mucosal candidiasis. In situ gel formulations were prepared and gelation temperature, rheological, mechanical and mucoadhesive properties, syringeability and release profiles were evaluated. Based on their suitable gelation temperature properties, formulations containing the poloxamer (Plx) 407 and 188 in ratios of 15:15 (F1), 15:20 (F2) and 20:10 (F3) were chosen for further studies. F3 exhibited typical gel-type mechanical spectra at 37 °C whereas F1 and F2 behaved like weakly cross-linked gels. Texture profile analysis demonstrated that F3 showed the highest cohesiveness, adhesiveness, hardness and compressibility. According to the these results, F3 was chosen for in vivo studies and it was shown that it is effective for the treatment of the vaginal candidiasis. Histopathologic evaluation also supported the effectiveness of the formulation. As a result, in situ gel formulations prepared with Plx 407 and 188 mixture of miconazole nitrate proved to be a promising alternative dosage form for treatment of mucosal candidiasisColegio de Farmacéuticos de la Provincia de Buenos Aire

Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis

Razvoj i karakterizacija mukoadhezivnih flastera salbutamol sulfata za jednosmjernu bukalnu isporuku

Buccal patches of salbutamol sulfate were prepared using five different water soluble polymers in various proportions and combinations using PEG-400/PG as plasticizers. A 32 full factorial design was used to design the experiments for each polymer combination. Patches were laminated on one side with a water impermeable backing layer for unidirectional drug release. The thickness of medicated patches ranged between 0.2 and 0.4 mm and showed an increase in mass whenever PEG-400 was used as plasticizer. The surface pH of all patches approached neutral. Eight formulations which had shown high folding endurance (> 300) were selected for evaluation. Patches prepared with PEG-400 showed a high swelling index. The residence time of the tested patches ranged between 105 and 130 min. Formulations A10, A32, B10 and B32 fitted the Higuchi model best, whereas formulations A19 and B19 showed super case II transport drug release. Stability studies indicated that there was no change in the chemical and physical characteristics during the test period of 6 months.U radu je opisana priprava flastera za bukalnu primjenu upotrebom različitih omjera pet vodotopljivih polimera i PEG-400/PG kao plastifikatora. Potpuni 32 faktorijalni dizajn upotrebljen je za dizajniranje eksperimenata za svaku kombinaciju polimera. Flasteri su postavljeni na jednu stranu usta s vodonepropusnom podlogom, koja omogućava jednosmjerno oslobađanje lijeka. Debljina flastera varirala je između 0,2 i 0,4 nm. Flasteri s PEG-400 bili su malo veće mase. pH na površini svih flastera bio je blizu neutralnog. Osam pripravaka vrlo otpornih na presavijanje (300) izabrano je za daljnju evaluaciju. Flasteri pripravljeni s PEG 400 imali su veliku sposobnost bubrenja. Flasteri su se zadržali na mjestu primjene između 105 i 130 min. Pripravci A10, A32, B10 i B32 najbolje su slijedili Higuchijev model, dok su pripravci A19 i B19 pokazivali anomalno oslobađanje koje ne slijedi Fickov zakon. Ispitivanje stabilnosti pokazalo je da ne postoje promjene u kemijskim i fizikalnim svojstvima pripravaka tijekom 6 mjeseci

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Utilização de nanopartículas no tratamento de feridas: revisão sistemática

RESUMO Objetivo: Analisar, com base nas evidências científicas, os efeitos dos curativos à base de nanopartículas no processo de cicatrização de feridas em animais e células humanas in vitro. Método: Revisão sistemática da literatura realizada nas bases de dados LILACS, PubMed e Science Direct. Os artigos foram selecionados e avaliados quanto ao nível de evidência pela aplicação do STROBE. Resultados: A amostra foi composta por 12 artigos. A aplicação dos produtos se deu em feridas cirúrgicas, queimaduras, feridas infectadas e úlceras gengivais em animais de laboratório, além de alguns testes in vitro, demonstrando que os curativos à base de nanopartículas aumentaram a velocidade de cicatrização, possuíam boa capacidade antibacteriana e não eram citotóxicos, dentre outras vantagens. Conclusão: Tomando por base os artigos analisados, pode-se afirmar que os curativos contendo nanocompostos são bastante promissores e mostramse como uma ótima opção terapêutica na cicatrização de feridas