Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs’ bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (∆η). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties.
Osteomyelitis is an inflammatory bone disorder caused by infection, leading to necrosis and destruction of bone. It can affect all ages, involve any bone, become a chronic disease and cause persistent morbidity. Treatment of osteomyelitis is challenging particularly when complex multiresistant bacterial biofilm has already been established. Bacteria in biofilm persist in a low metabolic phase, causing persistent infection due to increased resistance to antibiotics. Staphylococcus aureus and Staphylococcus epidermidis are the most common causative organism responsible for more than 50% of osteomyelitis cases. Osteomyelitis treatment implies the administration of high doses of antibiotics (AB) by means of endovenous and oral routes and should take a period of at least 6 weeks. Local drug delivery systems, using non-biodegradable (polymethylmethacrylate) or biodegradable and osteoactive materials such as calcium orthophosphates bone cements, have been shown to be promising alternatives for the treatment of osteomyelitis. These systems allow the local delivery of AB in situ with bactericidal concentrations for long periods of time and without the toxicity associated with other means of administration. This review examines the most recent literature evidence on the causes, pathogeneses and pharmacological treatment of osteomyelitis. A osteomielite é um processo inflamatório do tecido ósseo, de origem infecciosa, que resulta em destruição inflamatória, necrose e formação de novo osso. Pode aparecer em qualquer idade, afetar qualquer osso e tornar-se uma doença crônica com morbidade persistente. Apesar dos progressos na quimioterapia infecciosa, o tratamento da osteomielite é caro e difícil, em particular quando associada à presença de biofilmes bacterianos, especialmente de Staphylococcus aureus e Staphylococcus epidermidis. O tratamento da osteomielite inclui a administração de doses elevadas de antibióticos (AB) por via endovenosa e oral, durante um período de pelo menos 6 semanas. Os sistemas de veiculação localizada de fármacos, utilizando materiais não biodegradáveis (polimetilmetacrilato) ou biodegradáveis e osteoativos como os cimentos ósseos de ortofosfatos de cálcio e vidro bioativo, surgiram como uma alternativa promissora para o tratamento da osteomielite. Estes sistemas permitem a veiculação de AB in situ com concentrações bactericidas por longos períodos de tempo e sem a toxicidade associada às outras vias de administração. O presente trabalho propõe uma revisão da literatura relativa às causas, à patogenia e ao tratamento farmacológico da osteomielite. A metodologia do estudo da revisão consistiu numa pesquisa bibliográfica, nas bases de dados Google Scholar, Science Direct, Pubmed, Springer link, B-on. Foram revistos e analisados diversos artigos publicados desde o ano de 1979.Unitermos: Osteomielite/tratamento farmacológico. Osteomielite/terapia antimicrobial. Staphylococcus aureus/presença/osteomielite. Antibióticos/uso/tratamento da osteomielite.
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