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https://hdl.handle.net/1822/66981
Título: | Mitotane liposomes for potential treatment of adrenal cortical carcinoma: ex vivo intestinal permeation and in vivo bioavailability |
Autor(es): | Zancanella, Patricia Oliveira, Daniele M. L. Oliveira, Bonald H. de Woiski, Thiago D. Pinto, Cesar C. Santana, Maria H. A. Souto, Eliana B. Severino, Patrícia |
Palavras-chave: | Mitotane Liposomes Adrenal cortical carcinoma Spray-drying Intestinal absorption Bioavailability |
Data: | 19-Mai-2020 |
Editora: | Marcel Dekker Inc. |
Revista: | Pharmaceutical Development and Technology |
Citação: | Zancanella, Patricia; Oliveira, Daniele M. L.; Oliveira, Bonald H. de; Woiski, Thiago D.; Pinto, Cesar C.; Santana, Maria H. A.; Souto, Eliana; Severino, Patrícia, Mitotane liposomes for potential treatment of adrenal cortical carcinoma: ex vivo intestinal permeation and in vivo bioavailability. Pharmaceutical Development and Technology, 25(8), 949-961, 2020 |
Resumo(s): | The adrenal cortical carcinoma (ACC) treatment, for which mitotane (o,p-DDD) is the drug of choice, still remains a challenge both because of the well-known solubility problems of the drug, and its serious side effects. Mitotane is currently administered as oral tablets. The loading of mitotane into nanocarriers has been suggested as a way to circumvent the low solubility of the drug and its limited oral bioavailability. In this work, we have developed liposomes containing mitotane to enhance its intestinal absorption and oral bioavailability. Liposomes were produced by spray-drying of a mixture of phospholipids and the developed formulation was optimized by studying the degree of crystallinity, spray-drying conditions, phospholipid/mitotane ratio, and influence of mannitol in the hydrating ethanolic solution. An optimal liposomal formulation was produced with a phospholipid:mitotane combination (3.34:1), exhibiting a mean hydrodynamic diameter around 1m and spherical shape. The produced mitotane liposomes were re-suspended by hydrating the spray-dried powders in a stirred tank, and tested their intestinal permeability (ex vivo) and relative bioavailability (in vivo), against a free drug solution (with or without Trigliceril®CM). Our results support the conclusion that the loading of mitotane in liposomes enhanced its intestinal absorption and relative bioavailability. |
Tipo: | Artigo |
Descrição: | accepted manuscript |
URI: | https://hdl.handle.net/1822/66981 |
DOI: | 10.1080/10837450.2020.1762645 |
ISSN: | 1083-7450 |
e-ISSN: | 1097-9867 |
Versão da editora: | https://www.tandfonline.com/loi/iphd20 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_53736_1.pdf Acesso restrito! | 908,5 kB | Adobe PDF | Ver/Abrir |