Mitotane liposomes for potential treatment of adrenal cortical carcinoma:ex vivointestinal permeation andin vivobioavailability

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Zancanella, P (Author) Other; Oliveira, DML (Author) Other; de Oliveira, BH (Author) Other; Woiski, TD (Author) Other; Pinto, CC (Author) Other; Santana, MHA (Author) Other; Souto, EB (Author) Other; Severino, P (Author) Other

Journal

Title: Pharmaceutical Development and Technology

Vol. 25

Pages: 949-961

ISSN: 1083-7450

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00S-6F0

DOI: 10.1080/10837450.2020.1762645

Abstract (EN): 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 1 mu m 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(R)CM). Our results support the conclusion that the loading of mitotane in liposomes enhanced its intestinal absorption and relative bioavailability.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13