resumo
Bisphosphonates, used for a long time in osteoporosis management, are currently the target of intensive research, from pre-formulation studies to more advanced stages of clinical practice. This review presents an overview of the contributions of this family of compounds to human health, starting with the chemistry and clinical uses of bisphosphonates. Following this, their pharmacology is described, highlighting administration-borne handicaps and undesirable effects. The last three sections of the review describe the research efforts that seek to curb delivery-related issues and expand bisphosphonate use. Innovative routes and strategies of administration, such as nano-encapsulation for oral intake or injectable cements for local or in-bone delivery are presented, as well as the latest results of case studies or preclinical studies proposing new therapeutic indications for the clinically approved bisphosphonates. Finally, a selection of anti-infectious bisphosphonate new drug candidates is shown, with focus on the molecules reported in the last two decades.
palavras-chave
IN-VITRO EVALUATION; 1-PERCENT ALENDRONATE GEL; LOCAL-DRUG DELIVERY; NITROGEN-CONTAINING BISPHOSPHONATES; HIV-1 REVERSE-TRANSCRIPTASE; RHEUMATOID-ARTHRITIS; ZOLEDRONIC ACID; MEVALONATE PATHWAY; INTRAVENOUS BISPHOSPHONATE; OSTEOGENESIS IMPERFECTA
categoria
Chemistry, Medicinal
autores
Barbosa, JS; Paz, FAA; Braga, SS
nossos autores
Filipe Alexandre Almeida Paz
Investigador Principal
Jéssica Barbosa
Estudante de doutoramento
Susana Isabel Fonseca de Almeida Santos Braga
Investigadoragradecimentos
Thanks are due to the University of Aveiro and Foundation for Science and Technology/MCTES for the financial support for the QOPNA research Unit (FCT UID/QUI/00062/2019), to the associated laboratory LAQV-REQUIMTE (project reference UIDB/50006/2020) and to CICECO-Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020), through national founds and, where applicable, cofinanced by the FEDER, within the PT2020 Partnership Agreement, and to the Portuguese NMR Network. We also thank FCT for the Ph.D. grant No. PD/BD/135104/2017 to J.S.B.