Nanoparticles based on biocompatible methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG113-b-P(D,L)LAn) copolymers as potential vehicles for the anticancer agent oxaliplatin were prepared by a nanoprecipitation technique. It was demonstrated that an increase in the hydrophobic PLA block length from 62 to 173 monomer units leads to an increase of the size of nanoparticles from 32 to 56 nm. Small-angle X-ray scattering studies confirmed the “core-corona” structure of mPEG113-b-P(D,L)LAn nanoparticles and oxaliplatin loading. It was suggested that hydrophilic oxaliplatin is adsorbed on the core-corona interface of the nanoparticles during the nanoprecipitation process. The oxaliplatin loading content decreased from 3.8 to 1.5% wt./wt. (with initial loading of 5% wt./wt.) with increasing PLA block length. Thus, the highest loading content of the anticancer drug oxaliplatin with its encapsulation efficiency of 76% in mPEG113-b-P(D,L)LAn nanoparticles can be achieved for block copolymer with short hydrophobic block.
The
effect of the hydrophobic block length in diblock (PLLA
x
-b-PEO113, x = 64, 166, 418) and triblock (PLLA
y
-b-PEO91-b-PLLA
y
, y = 30, 52, 120) copolymers
of l-lactic acid and ethylene oxide on the structure of micelles
prepared by dialysis was studied by wide- and small-angle X-ray scattering
in dilute aqueous solution, dynamic light scattering, transmission
electron microscopy, atomic force microscopy, and force spectroscopy.
It was found that the size of the crystalline PLLA core is weakly
dependent on the PLLA block length. In addition to individual micelles,
a number of their micellar clusters were detected with characteristic
distance between adjacent micelle cores decreasing with an increase
in PLLA block length. This effect was explained by the change in the
conformation of PEO chains forming the micellar corona because of
their overcrowding. Force spectroscopy experiments also reveal a more
stretched conformation of the PEO chains for the block copolymers
with a shorter PLLA block. A model describing the structure of the
individual micelles and their clusters was proposed.
Modern pharmaceutics are actively developing towards the design of targeted drugs. The development of selectively acting formulations requires the creation of smart delivery systems based on carriers that would first find the target cells and enter them and then release the active substance locally. Nanoparticles of biocompatible and biodegradable polymers can be effectively used as such carriers. Flexible regulation of the molecular structure and architecture of polymers, as well as the modification of nanoparticles with vector molecules, allows one to construct carrier particles for the development of nanoformulations for active agents of various nature. This review presents the main approaches to the design of nanoformulations for targeted delivery, describes the methods for the preparation and study of nanoparticles based on hydrophobic and amphiphilic biodegradable lactide polymers, and discusses the effect of the molecular structure and preparation conditions on the characteristics of nanoparticles in detail. Some results of research in this area of the Kurchatov complex of NBIСS nature-like technologies are also presented.
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