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The Effect of Polymerization Method in Stereo-active Block Copolymers on the Stability of Polymeric Micelles and their Drug Release Profile

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Abstract

Purpose

To investigate the effect of polymerization method on the stability and drug release properties of polymeric micelles formed using stereo-active block copolymers.

Methods

Diblock copolymers consisting of methoxy poly ethylene oxide (MePEO) and poly(lactide)s (PLA)s of different stereochemistry were synthesized by bulk or solution polymerization. Polymers and micelles were characterized for their chemical structure by 1H NMR, optical rotation by polarimetry, critical micellar concentration by fluorescence spectroscopy, thermal properties by differential scanning calorimetry, morphology by transmission electron microscopy and size as well as kinetic stability by dynamic light scattering. Release of encapsulated nimodipine from polymeric micelles at different levels of loading was also investigated.

Results

Solution polymerization yielded a higher degree of crystallinity for stereo-regular PLA blocks. Consequently, the related polymeric micelles were kinetically more stable than those prepared by bulk polymerization. At high drug loading levels, the release of nimodipine was more rapid from polymeric micelles with crystalline cores. At lower levels of drug loading, drug release was slower and independent of the stereochemistry of the core.

Conclusions

The results underline the effect of polymerization method in defining core crystallinity in stereoregular block copolymer micelles. It also shows the impact of core crystallinity on enhancing micellar stability and drug release.

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Abbreviations

CMC:

Critical micellar concentration

DL:

Drug loading

DLS:

Dynamic light scattering

DMSO:

Dimethyl sulfoxide

DSC:

Differential scanning calorimetry

EE:

Encapsulation efficiency

MD:

Molecular dynamic

Mn:

Number average molecular weight

NMR:

Nuclear magnetic resonance spectroscopy

PDLA:

Poly(D-lactide)

PD/LLA:

Poly(D/L-lactide)

PDLLA:

50–50 poly(D,L-lactide)

PEG:

Poly ethylene glycol

PEO:

Poly ethylene oxide

PI:

Polydispersity index

PLA:

Poly lactide

PLLA:

Poly(L-lactide)

RAC:

Racemic

ROP:

Ring opening polymerization

SnO2 :

Stannous octoate (tin(II) bis(2-ethylhexanoate))

SDS:

Sodium dodecyl sulfate

TEM:

Transmission electron microscopy

THF:

Tetrahydrofuran

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Acknowledgements And Disclosures

This study was supported by grants from Natural Science and Engineering Council of Canada (NSERC). A.L. also acknowledges support from Canadian Foundation for Innovation (CFI) and Alberta Advanced Education and Technology (AAET) for the infrastructure used in the study.

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Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada

    Hoda Soleymani Abyaneh, Mohammad Reza Vakili & Afsaneh Lavasanifar

  2. Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada

    Afsaneh Lavasanifar

Authors
  1. Hoda Soleymani Abyaneh
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  2. Mohammad Reza Vakili
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  3. Afsaneh Lavasanifar
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Correspondence to Afsaneh Lavasanifar.

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Soleymani Abyaneh, H., Vakili, M.R. & Lavasanifar, A. The Effect of Polymerization Method in Stereo-active Block Copolymers on the Stability of Polymeric Micelles and their Drug Release Profile. Pharm Res 31, 1485–1500 (2014). https://doi.org/10.1007/s11095-013-1255-5

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