Exploration of docetaxel palmitate and its solid lipid nanoparticles as a novel option for alleviating the rising concern of multi-drug resistance.
Animals
Antineoplastic Agents
/ administration & dosage
Apoptosis
/ drug effects
Cell Survival
/ drug effects
Docetaxel
/ administration & dosage
Drug Liberation
Drug Resistance, Multiple
/ drug effects
Drug Resistance, Neoplasm
/ drug effects
Erythrocytes
/ drug effects
Female
Humans
Lipids
/ administration & dosage
MCF-7 Cells
Male
Mammary Neoplasms, Experimental
/ drug therapy
Mice, Inbred BALB C
Nanoparticles
/ administration & dosage
Rats, Wistar
Serum Albumin, Human
/ chemistry
Computational studies
Drug conjugate
In-vivo tumor
Pharmacokinetics
SLNs
Taxanes
Journal
International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127
Informations de publication
Date de publication:
30 Mar 2020
30 Mar 2020
Historique:
received:
01
08
2019
revised:
23
01
2020
accepted:
24
01
2020
pubmed:
1
2
2020
medline:
1
12
2020
entrez:
1
2
2020
Statut:
ppublish
Résumé
Docetaxel (DTX), a widely prescribed anticancer agent, is now associated with increased instances of multidrug resistance. Also, being a problematic BCS class IV drug, it poses challenges for the formulators. Henceforth, it was envisioned to synthesize an analogue of DTX with a biocompatible lipid, i.e., palmitic acid. The in-silico studies (molecular docking and simulation) inferred lesser binding of docetaxel palmitate (DTX-PL) with P-gp vis-à-vis DTX and paclitaxel, indicating it to be a poor substrate for P-gp efflux. Solid lipid nanoparticles (SLNs) of the conjugate were prepared using various lipids, viz. palmitic acid, stearic acid, cetyl palmitate and glyceryl monostearate. The characterization studies for the nanocarrier were performed for the surface charge, drug payload, micromeritics, release pattern of drug and surface morphology. From the cytotoxicity assays on resistant MCF-7 cells, it was established that the new analogue offered substantially decreased IC
Identifiants
pubmed: 32001291
pii: S0378-5173(20)30072-7
doi: 10.1016/j.ijpharm.2020.119088
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Lipids
0
Docetaxel
15H5577CQD
Serum Albumin, Human
ZIF514RVZR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
119088Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.