RESUMO
The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (e.g. pain, needle-stick injuries or needle re-use). This review focuses on dissolving microneedles that after penetration into the skin dissolve releasing the encapsulated antigen. The microneedle patch fabrication techniques and their challenges are discussed as well as the microneedle characterization methods and antigen stability aspects. The immunogenicity of antigens formulated in dissolving microneedles are addressed. Finally, the early clinical development is discussed.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Agulhas , Adesivo Transdérmico , Vacinação/métodos , Vacinas/administração & dosagem , Administração Cutânea , Animais , Antígenos/imunologia , Humanos , Imunização , Pele/metabolismoRESUMO
Star-shaped poly(epsilon-caprolactone) oligomers functionalized with succinic anhydride were used as prepolymers to prepare photocrosslinked poly(ester anhydride) to evaluate their in vivo drug delivery functionality and biocompatibility. Thus, in this work, erosion, drug release and safety of the photocrosslinked poly(ester anhydride) were examined in vitro and in vivo. A small water-soluble drug, propranolol HCl (M(w) 296 g/mol, solubility 50 mg/ml), was used as the model drug in an evaluation of the erosion controlled release. Drug-free and drug-loaded (10-60% w/w) poly(ester anhydride) discoids eroded in vitro (pH 7.4 buffer, +37 degrees C) linearly within 24-48 h. A strong correlation between the polymer erosion and the linear drug release in vitro was observed, indicating that the release had been controlled by the erosion of the polymer. Similarly, in vivo studies (s.c. implantation of discoids in rats) indicated that surface erosion controlled drug release from the discoids (drug loading 40% w/w). Oligomers did not decrease cell viability in vitro and the implanted discoids (s.c., rats) did not evoke any cytokine activity in vivo. In summary, surface erosion controlled drug release and the safety of photocrosslinked poly(ester anhydride) were demonstrated in this study.