Hyaluronated imatinib liposomes with hybrid approach to target CD44 and P-gp overexpressing MDR cancer: an in-vitro, in-vivo and mechanistic investigation.
J Drug Target
; 27(2): 183-192, 2019 02.
Article
en En
| MEDLINE
| ID: mdl-29972336
ABSTRACT
Multi Drug Resistance (MDR) of cancer cells is a constant threat to the clinically used drugs as well as new drug development. In present work, we aimed to assess in-vitro as well as in-vivo efficacy of the developed Imatinib loaded liposomes in MDR cancer. An array of tests was also carried out to comprehensively understand the bio-mechanism that enable these nanocarriers to modulate P-gp activity. Hyaluronic acid coated, Imatinib mesylate containing lipsomes (HA-LIPO-IM) were analysed through in-vitro and in-vivo studies in MDR cancer cells and tumour models. Effect of developed hyaluronated liposomes on various biomolecular mechanisms was also evaluated. Around 3.5 times lower IC50 for HA-LIPO-IM in comparison to drug solution in HT-29 and Colo-320 cells proved the enhanced action of the drug in MDR cells. HA-LIPO formulations were demonstrated to have inhibitory effect on ATPase enzyme. Molecular masking of Imatinib mesylate and CD-44 mediated endocytosis were also found responsible for anti-MDR effect. In-vivo studies revealed the prolonged tumour accumulation and 4-fold increase in tumour regression efficacy of HA-LIPO-IM in comparison to free drug solution. The work demonstrated the target specific accumulation of HA-LIPO-IM in CD-44 overexpressing cancer cells through P-gp modulation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
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Resistencia a Antineoplásicos
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Receptores de Hialuranos
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Mesilato de Imatinib
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Antineoplásicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Drug Target
Asunto de la revista:
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
India