Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles

Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations.

[1]  Joseph M DeSimone,et al.  Top-down particle fabrication: control of size and shape for diagnostic imaging and drug delivery. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[2]  E. Allémann,et al.  Nanoprecipitation versus emulsion-based techniques for the encapsulation of proteins into biodegradable nanoparticles and process-related stability issues , 2005, AAPS PharmSciTech.

[3]  Daniel Forciniti.  Preparation of Aqueous Two-Phase Systems , 2000 .

[4]  Charles R. Mace,et al.  Aqueous multiphase systems of polymers and surfactants provide self-assembling step-gradients in density. , 2012, Journal of the American Chemical Society.

[5]  David A Weitz,et al.  Microfluidic fabrication of water-in-water (w/w) jets and emulsions. , 2012, Biomicrofluidics.

[6]  Nicholas A Peppas,et al.  Micro- and nanotechnologies for intelligent and responsive biomaterial-based medical systems. , 2009, Advanced drug delivery reviews.

[7]  Wilhelm T S Huck,et al.  Fabrication of microgel particles with complex shape via selective polymerization of aqueous two-phase systems. , 2012, Small.

[8]  Samir Mitragotri,et al.  Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[9]  Philip C Bevilacqua,et al.  Bioreactor droplets from liposome-stabilized all-aqueous emulsions , 2014, Nature Communications.

[10]  Sung‐Wook Choi,et al.  Preparation of poly(NIPAAm)-Pluronic F68 as a thermosensitive surfactant for a controlled drug release , 2011, International journal of pharmaceutical investigation.

[11]  T. A. Hatton,et al.  Poly(ethylene oxide)-poly(propylene oxide )-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling , 1995 .

[12]  H. Hoffmann,et al.  Phase Diagrams and Aggregation Behavior of Poly(oxyethylene)-Poly(oxypropylene)-Poly(oxyethylene) Triblock Copolymers in Aqueous Solutions , 1994 .

[13]  Hirenkumar K. Makadia,et al.  Poly Lactic-co-Glycolic Acid ( PLGA ) as Biodegradable Controlled Drug Delivery Carrier , 2011 .

[14]  Shuichi Takayama,et al.  Aqueous two-phase systems enable multiplexing of homogeneous immunoassays. , 2014, Technology.

[15]  J. Hsu,et al.  Phase diagrams for dextran-peg aqueous two-phase systems at 22°C , 1989 .

[16]  V. Préat,et al.  PLGA-based nanoparticles: an overview of biomedical applications. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Reinhard Vehring,et al.  Pharmaceutical Particle Engineering via Spray Drying , 2007, Pharmaceutical Research.

[18]  P. Albertsson,et al.  Partition of cell particles and macromolecules in polymer two-phase systems. , 1970, Advances in protein chemistry.

[19]  Young-Soo Han,et al.  SANS study on self-assembled structures of Pluronic F127 triblock copolymer induced by additives and temperature , 2014 .

[20]  S. Takayama,et al.  Microscale determination of aqueous two phase system binodals by droplet dehydration in oil. , 2013, Analytical chemistry.

[21]  B. Mosadegh,et al.  Nanoliter Liquid Patterning in Aqueous Environments for Spatially-defined Reagent Delivery to Mammalian Cells Hhs Public Access , 2022 .

[22]  Alexander V Kabanov,et al.  Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[23]  Surya K. Mallapragada,et al.  Synthesis and Characterization of Ionic Block Copolymer Templated Calcium Phosphate Nanocomposites , 2008 .

[24]  Fei Wu,et al.  Polymersomes of asymmetric bilayer membrane formed by phase-guided assembly. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[25]  S. Takayama,et al.  Aqueous two-phase system patterning of detection antibody solutions for cross-reaction-free multiplex ELISA , 2014, Scientific Reports.

[26]  Tejraj M Aminabhavi,et al.  Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Antonios G Mikos,et al.  Thermoresponsive hydrogels in biomedical applications. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[28]  Christine D. Keating,et al.  Aqueous Phase Separation as a Possible Route to Compartmentalization of Biological Molecules , 2012, Accounts of chemical research.