Highly loaded deoxypodophyllotoxin nano-formulation delivered by methoxy polyethylene glycol-block-poly (D,L-lactide) micelles for efficient cancer therapy

Autor: Yu Caiwei, Yi Li, Birendra Chaurasiya, Yinglan Yu, Chang Zu, Jiasheng Tu, Yan Shen, Baoqiang Tang, Runing Sun, Daquan Chen
Rok vydání: 2020
Předmět:
Male
Time Factors
Polyesters
lyophilization
Cancer therapy
Mice
Nude
Pharmaceutical Science
RM1-950
02 engineering and technology
Polyethylene glycol
030226 pharmacology & pharmacy
Micelle
Polyethylene Glycols
Nano formulation
Mice
03 medical and health sciences
Human health
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
Cell Line
Tumor
Neoplasms
otorhinolaryngologic diseases
Animals
Humans
Tissue Distribution
Particle Size
anti-tumor
Micelles
deoxypodophyllotoxin
Podophyllotoxin
polymeric micelles
Antitumor activity
Polymeric micelles
mpeg-pdlla
General Medicine
021001 nanoscience & nanotechnology
Antineoplastic Agents
Phytogenic
Combinatorial chemistry
Freeze Drying
chemistry
Nanoparticles
Poly d l lactide
Therapeutics. Pharmacology
0210 nano-technology
Drugs
Chinese Herbal
Research Article
Zdroj: Drug Delivery, Vol 27, Iss 1, Pp 248-257 (2020)
Drug Delivery
ISSN: 1521-0464
1071-7544
DOI: 10.1080/10717544.2020.1716875
Popis: Cancer is a kind of malignant diseases that threatens human health and the research application of anti-tumor drug therapeutics is growingly always been focused on. Many new compounds with great anticancer activity were synthesized but cannot be hard to be developed into clinical use due to its poor water solubility. Deoxypodophyllotoxin (DPT) is just an example. We develop lyophilized Deoxypodophyllotoxin (DPT) loaded polymeric micelles using methoxy polyethylene glycol-block-Poly (D, L-lactide) (mPEG-PLA). DPT-PM freeze-dried powder was successfully prepared using optimized formulation. mPEG-PLA was added to hydration media before hydrating as cryoprotectants. The freeze-dried powder exhibited white pie-solid without collapsing, and the particle size of DPT-PM reconstituted with water was about 20-35 nm. The entrapment efficiency of the reconstituted solution was 98%, which shows no differences with the micelles before lyophilization. In-vitro cytotoxicity and cellular uptake studies showed that DPT-PM has a higher degree of cytotoxicity comparing with DPT and mPEG-PLA micelles and uptake of mPEG-PLA was concentration and time-dependent. In vivo characterization of DPT-PM was done for pharmacokinetics behaviors, antitumor activity and safety. The obtained results showed significant improvement in plasma clearance bioavailability (p
Databáze: OpenAIRE
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