Docetaxel-loaded human serum albumin (HSA) nanoparticles: synthesis, characterization, and evaluation.
Controlled release
Cytotoxicity
Docetaxel
Human serum albumin
Maximum tolerated dose
Nanoparticles
Self-assembly
Journal
Biomedical engineering online
ISSN: 1475-925X
Titre abrégé: Biomed Eng Online
Pays: England
ID NLM: 101147518
Informations de publication
Date de publication:
31 Jan 2019
31 Jan 2019
Historique:
received:
26
10
2018
accepted:
12
01
2019
entrez:
2
2
2019
pubmed:
2
2
2019
medline:
15
6
2019
Statut:
epublish
Résumé
Docetaxel (DTX) is an anticancer drug that is currently formulated with polysorbate 80 and ethanol (50:50, v/v) in clinical use. Unfortunately, this formulation causes hypersensitivity reactions, leading to severe side-effects, which have been primarily attributed to polysorbate 80. In this study, a DTX-loaded human serum albumin (HSA) nanoparticle (DTX-NP) was designed to overcome the hypersensitivity reactions that are induced by polysorbate 80. The methods of preparing the DTX-NPs have been optimized based on factors including the drug-to-HSA weight ratio, the duration of HSA incubation, and the choice of using a stabilizer. Synthesized DTX-NPs were characterized with regard to their particle diameters, drug loading capacities, and drug release kinetics. The morphology of the DTX-NPs was observed via scanning electron microscopy (SEM) and the successful preparation of DTX-NPs was confirmed via differential scanning calorimetry (DSC). The cytotoxicity and cellular uptake of DTX-NPs were investigated in the non-small cell lung cancer cell line A549 and the maximum tolerated dose (MTD) of DTX-NPs was evaluated via investigations with BALB/c mice. The study showed that the loading capacity and the encapsulation efficiency of DTX-NPs prepared under the optimal conditions was 11.2 wt% and 63.1 wt%, respectively and the mean diameter was less than 200 nm, resulting in higher permeability and controlled release. Similar cytotoxicity against A549 cells was exhibited by the DTX-NPs in comparison to DTX alone while higher maximum tolerated dose (MTD) with the DTX-NPs (75 mg/kg) than with DTX (30 mg/kg) was demonstrated in mice, suggesting that the DTX-NPs prepared with HSA yielded similar anti-tumor activity but were accompanied by less systemic toxicity than solvent formulated DTX. DTX-NPs warrant further investigation and are promising candidates for clinical applications.
Sections du résumé
BACKGROUND
BACKGROUND
Docetaxel (DTX) is an anticancer drug that is currently formulated with polysorbate 80 and ethanol (50:50, v/v) in clinical use. Unfortunately, this formulation causes hypersensitivity reactions, leading to severe side-effects, which have been primarily attributed to polysorbate 80.
METHODS
METHODS
In this study, a DTX-loaded human serum albumin (HSA) nanoparticle (DTX-NP) was designed to overcome the hypersensitivity reactions that are induced by polysorbate 80. The methods of preparing the DTX-NPs have been optimized based on factors including the drug-to-HSA weight ratio, the duration of HSA incubation, and the choice of using a stabilizer. Synthesized DTX-NPs were characterized with regard to their particle diameters, drug loading capacities, and drug release kinetics. The morphology of the DTX-NPs was observed via scanning electron microscopy (SEM) and the successful preparation of DTX-NPs was confirmed via differential scanning calorimetry (DSC). The cytotoxicity and cellular uptake of DTX-NPs were investigated in the non-small cell lung cancer cell line A549 and the maximum tolerated dose (MTD) of DTX-NPs was evaluated via investigations with BALB/c mice.
RESULTS
RESULTS
The study showed that the loading capacity and the encapsulation efficiency of DTX-NPs prepared under the optimal conditions was 11.2 wt% and 63.1 wt%, respectively and the mean diameter was less than 200 nm, resulting in higher permeability and controlled release. Similar cytotoxicity against A549 cells was exhibited by the DTX-NPs in comparison to DTX alone while higher maximum tolerated dose (MTD) with the DTX-NPs (75 mg/kg) than with DTX (30 mg/kg) was demonstrated in mice, suggesting that the DTX-NPs prepared with HSA yielded similar anti-tumor activity but were accompanied by less systemic toxicity than solvent formulated DTX.
CONCLUSIONS
CONCLUSIONS
DTX-NPs warrant further investigation and are promising candidates for clinical applications.
Identifiants
pubmed: 30704488
doi: 10.1186/s12938-019-0624-7
pii: 10.1186/s12938-019-0624-7
pmc: PMC6357434
doi:
Substances chimiques
Drug Carriers
0
Docetaxel
15H5577CQD
Serum Albumin, Human
ZIF514RVZR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11Subventions
Organisme : National Natural Science Foundation of China
ID : 31700713
Organisme : Department of Science and Technology of Jilin Province
ID : 20170520034JH
Organisme : Education Department of Jilin Province
ID : JJKH20180174KJ
Organisme : Key platform and Major Research Program of Guangdong Provincial University
ID : 2017GXJK221
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