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Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery
- Source :
- International Journal of Nanomedicine
- Publication Year :
- 2017
-
Abstract
- Yutong Wang,1–3,* Liping Huang,1,2,* Yan Shen,1,2,* Lidan Tang,1,2,4 Runing Sun,1,5 Di Shi,6 Thomas J Webster,6 Jiasheng Tu,1,2 Chunmeng Sun1,2 1Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, China Pharmaceutical University, 2State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 3Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 4Changzhou Second People’s Hospital, Changzhou, 5School of Engineering, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA *These authors contributed equally to this work Abstract: To achieve enhanced physical stability of poly(ethylene glycol)-poly(D,L-lactide) polymeric micelles (PEG-PDLLA PMs), a mixture of methoxy PEG-PDLLA-polyglutamate (mPEG-PDLLA-PLG) and mPEG-PDLLA-poly(L-lysine) (mPEG-PDLLA-PLL) copolymers was applied to self-assembled stable micelles with polyion-stabilized cores. Prior to micelle preparation, the synthetic copolymers were characterized by 1H-nuclear magnetic resonance (NMR) and infrared spectroscopy (IR), and their molecular weights were calculated by 1H-NMR and gel permeation chromatography (GPC). Dialysis was used to prepare PMs with deoxypodophyllotoxin (DPT). Transmission electron microscopy (TEM) images showed that DPT polyion complex micelles (DPT-PCMs) were spherical, with uniform distribution and particle sizes of 36.3±0.8nm. In addition, compared with nonpeptide-modified DPT-PMs, the stability of DPT-PCMs was significantly improved under various temperatures. In the meantime, the pH sensitivity induced by charged peptides allowed them to have a stronger antitumor effect and a pH-triggered release profile. As a result, the dynamic characteristic of DPT-PCM was retained, and high biocompatibility of DPT-PCM was observed in an in vivo study. These results indicated that the interaction of anionic and cationic charged polyionic segments could be an effective strategy to control drug release and to improve the stability of polymer-based nanocarriers. Keywords: polyion complex micelles, electrostatic interaction, oligopeptide, stability, pharmacokinetics
- Subjects :
- Male
Magnetic Resonance Spectroscopy
Proton Magnetic Resonance Spectroscopy
Pharmaceutical Science
02 engineering and technology
01 natural sciences
Micelle
Polyethylene Glycols
Gel permeation chromatography
Rats, Sprague-Dawley
chemistry.chemical_compound
International Journal of Nanomedicine
oligopeptide
Drug Discovery
Polylysine
Micelles
Podophyllotoxin
Original Research
chemistry.chemical_classification
Drug Carriers
Temperature
General Medicine
Polymer
Hydrogen-Ion Concentration
021001 nanoscience & nanotechnology
Biochemistry
Polyglutamic Acid
electrostatic interaction
Rabbits
0210 nano-technology
Drug carrier
pharmacokinetics
Polyesters
polyion complex micelles
Static Electricity
Biophysics
Bioengineering
010402 general chemistry
complex mixtures
Biomaterials
otorhinolaryngologic diseases
Animals
Particle Size
Organic Chemistry
Cationic polymerization
stability
0104 chemical sciences
Molecular Weight
Drug Liberation
chemistry
Chemical engineering
Nanocarriers
Ethylene glycol
Drugs, Chinese Herbal
Subjects
Details
- ISSN :
- 11782013
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- International journal of nanomedicine
- Accession number :
- edsair.doi.dedup.....466c423f0a721ce753563f000fec0b0f