Solubilization of therapeutic agents in micellar nanomedicines.
Langmuir
; 29(51): 15747-54, 2013 Dec 23.
Article
em En
| MEDLINE
| ID: mdl-24283508
ABSTRACT
We use atomistic molecular dynamics simulations to reveal the binding mechanisms of therapeutic agents in PEG-ylated micellar nanocarriers (SSM). In our experiments, SSM in buffer solutions can solubilize either ≈11 small bexarotene molecules or ≈6 (2 in low ionic strength buffer) human vasoactive intestinal peptide (VIP) molecules. Free energy calculations reveal that molecules of the poorly water-soluble drug bexarotene can reside at the micellar ionic interface of the PEG corona, with their polar ends pointing out. Alternatively, they can reside in the alkane core center, where several bexarotene molecules can self-stabilize by forming a cluster held together by a network of hydrogen bonds. We also show that highly charged molecules, such as VIP, can be stabilized at the SSM ionic interface by Coulombic coupling between their positively charged residues and the negatively charged phosphate headgroups of the lipids. The obtained results illustrate that atomistic simulations can reveal drug solubilization character in nanocarriers and be used in efficient optimization of novel nanomedicines.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidronaftalenos
/
Portadores de Fármacos
/
Nanoestruturas
/
Nanomedicina
/
Simulação de Dinâmica Molecular
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Micelas
Limite:
Humans
Idioma:
En
Revista:
Langmuir
Assunto da revista:
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos