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Advisor(s)
Abstract(s)
A administração ocular de fármacos constitui, ainda nos dias de hoje, um desafio devido à complexa arquitetura do olho. Atualmente, grande parte das formulações comercializadas apresentam-se sob a forma de colírio, não só devido à sua simplicidade de utilização e pela elevada adesão por parte do doente, mas também pelo facto de se tratar de uma solução terapêutica não invasiva. No entanto, a biodisponibilidade ocular dos fármacos administrados topicamente é limitada, tanto pelas propriedades físico-químicas pouco favoráveis das substâncias ativas, como pelos diversos mecanismos de proteção do olho, que são responsáveis por impedir a entrada de xenobióticos. Se por um lado, os tratamentos tópicos convencionais não conseguem entregar o fármaco no local de ação pretendido, por outro, as injeções intravítreas entregam o fármaco diretamente na cavidade vítrea. Contudo, injeções frequentes podem provocar efeitos adversos como por exemplo, descolamento da retina, endoftalmite e hemorragia na retina. Deste modo, torna-se urgente continuar a investigar formas para melhorar a penetração na estrutura ocular, aumentar a biodisponibilidade do fármaco e prolongar o tempo de retenção na superfície ocular. Nos últimos anos, novos sistemas de veiculação de fármacos foram propostos para contornar os principais problemas das formulações oftálmicas convencionais. As nanopartículas surgiram como transportadores promissores, dando origem a colírios e soluções injetáveis “modificados” com o objetivo de melhorar a eficácia do medicamento, sem comprometer a sua segurança e a adesão do doente. Esta revisão aborda não só os diferentes fatores envolvidos no desenvolvimento de nanopartículas como sistemas veiculadores de fármacos, com especial ênfase nas nanopartículas poliméricas, lipídicas e nas de ouro, como também os desafios regulamentares implicados no desenvolvimento das nanopartículas. Por fim, são apresentadas algumas orientações adicionais publicadas pela Agência Europeia do Medicamento, de forma a ultrapassar determinadas questões regulamentares devido à natureza multidisciplinar dos sistemas nanoparticulados com aplicações no campo terapêutico de determinadas patologias oculares.
Ocular drug administration still remains a challenge nowadays due to the complex architecture of the eye. Currently, most of the commercialized formulations are presented in the form of eye drops, not only due to their simplicity of use and the high compliance by the patient, but also because it is a non-invasive therapeutic solution. However, the ocular bioavailability of topically administered drugs is limited, both by the unfavorable physicochemical properties of the active substances, and by the various protective mechanisms of the eye, which are responsible for preventing the entry of xenobiotics. If, on the one hand, conventional topical treatments fail to deliver the drug to the intended site of action, on the other, intravitreal injections deliver the drug directly to the vitreous cavity. However, frequent injections can cause adverse effects such as retinal detachment, endophthalmitis and retinal hemorrhage. Thus, there is an urgent need to continue investigating ways to improve penetration into the ocular structure, increase bioavailability and prolong the retention time on the ocular surface. In recent years, new drug delivery systems have been proposed to overcome the main problems of conventional ophthalmic formulations. Nanoparticles have emerged as promising carriers, giving rise to “modified” eye drops and injectable solutions with the aim of improving the effectiveness of the drug, without compromising its safety and patient compliance. This review addresses not only the different factors involved in the development of nanoparticles as drug delivery systems, with a special emphasis on polymeric, lipidic and gold nanoparticles, but also the regulatory challenges involved in the development of nanoparticles. Finally, some additional guidelines published by the European Medicines Agency are presented in order to overcome certain regulatory issues due to the multidisciplinary nature of nanoparticulate systems with applications in the therapeutic field of certain ocular pathologies.
Ocular drug administration still remains a challenge nowadays due to the complex architecture of the eye. Currently, most of the commercialized formulations are presented in the form of eye drops, not only due to their simplicity of use and the high compliance by the patient, but also because it is a non-invasive therapeutic solution. However, the ocular bioavailability of topically administered drugs is limited, both by the unfavorable physicochemical properties of the active substances, and by the various protective mechanisms of the eye, which are responsible for preventing the entry of xenobiotics. If, on the one hand, conventional topical treatments fail to deliver the drug to the intended site of action, on the other, intravitreal injections deliver the drug directly to the vitreous cavity. However, frequent injections can cause adverse effects such as retinal detachment, endophthalmitis and retinal hemorrhage. Thus, there is an urgent need to continue investigating ways to improve penetration into the ocular structure, increase bioavailability and prolong the retention time on the ocular surface. In recent years, new drug delivery systems have been proposed to overcome the main problems of conventional ophthalmic formulations. Nanoparticles have emerged as promising carriers, giving rise to “modified” eye drops and injectable solutions with the aim of improving the effectiveness of the drug, without compromising its safety and patient compliance. This review addresses not only the different factors involved in the development of nanoparticles as drug delivery systems, with a special emphasis on polymeric, lipidic and gold nanoparticles, but also the regulatory challenges involved in the development of nanoparticles. Finally, some additional guidelines published by the European Medicines Agency are presented in order to overcome certain regulatory issues due to the multidisciplinary nature of nanoparticulate systems with applications in the therapeutic field of certain ocular pathologies.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Sistemas de veiculação de fármacos Nanopartículas Via oftálmica Segmento anterior Segmento posterior Mestrado integrado - 2020