Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir

Li, Ziang; Lenk, Theodore I.; Yao, Letitia J.; Bates, Frank S.; Lodge, Timothy P.

doi:10.1021/acs.macromol.7b02297

Title: Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir

Abstract

In this work, two poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PND) statistical copolymers and a series of three poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)- b-polystyrene (PND-b-PS-C12) diblock polymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, in which the molecular weight of the thermoresponsive PND corona block was held constant while the polystyrene core block length was varied. The corona thickness and density of the micelles in phosphate-buffered saline (PBS, pH = 6.5) were quantified by a combination of dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Two hydrophobic model drugs, phenytoin and nilutamide, were used to examine the drug-polymer interactions in aqueous solution. Intermolecular interactions between the diblock polymer micelle corona and both drugs were revealed by 2D 1H nuclear Overhauser effect spectroscopy (NOESY). The drug-polymer “binding” strength, quantified by diffusion ordered NMR spectroscopy (DOSY), increased as corona density of the diblock polymer micelle increased for both drugs. The in vitro dissolution of the amorphous solid dispersions was systematically investigated as a function of drug type, drug loading, and the solution-state assembly of the polymers by using either a selective or nonselective spray drying solvent. Forming micelles prior to spray drying significantly enhanced phenytoin dissolution and supersaturation maintenance for the diblock polymers by storing the drug moleculesmore » in the corona.« less

Authors:

Li, Ziang ^[1]; Lenk, Theodore I. ^[1]; Yao, Letitia J. ^[1];

^[1];

^[1]

Univ. of Minnesota, Minneapolis, MN (United States)

Publication Date:: Wed Jan 03 00:00:00 EST 2018

Research Org.:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: The Dow Chemical Company; E.I. DuPont de Nemours & Co.; Northwestern University; USDOE Office of Science (SC); National Science Foundation (NSF); European Union’s Horizon 2020; National Institutes of Health (NIH)

OSTI Identifier:: 1424788

Grant/Contract Number:: AC02-06CH11357; DMR-0520547; 654000; DMR-1420013; S10OD011952

Resource Type:: Accepted Manuscript

Journal Name:: Macromolecules

Additional Journal Information:: Journal Volume: 51; Journal Issue: 2; Journal ID: ISSN 0024-9297

Publisher:: American Chemical Society

Country of Publication:: United States

Language:: ENGLISH

Subject:: 60 APPLIED LIFE SCIENCES; Hydrocarbons; Micelles; Dissolution; Aromatic compounds; Polymers

Citation Formats


                    Li, Ziang, Lenk, Theodore I., Yao, Letitia J., Bates, Frank S., and Lodge, Timothy P. Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir.  United States: N. p., 2018. 
Web.  doi:10.1021/acs.macromol.7b02297.

Copy to clipboard


                    Li, Ziang, Lenk, Theodore I., Yao, Letitia J., Bates, Frank S., & Lodge, Timothy P. Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir.  United States.  https://doi.org/10.1021/acs.macromol.7b02297

Copy to clipboard


                    Li, Ziang, Lenk, Theodore I., Yao, Letitia J., Bates, Frank S., and Lodge, Timothy P. Wed .  
"Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir".  United States.  https://doi.org/10.1021/acs.macromol.7b02297.  https://www.osti.gov/servlets/purl/1424788.

Copy to clipboard


                    
@article{osti_1424788,

  title        = {Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir},

  author       = {Li, Ziang and Lenk, Theodore I. and Yao, Letitia J. and Bates, Frank S. and Lodge, Timothy P.},

  abstractNote = {In this work, two poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PND) statistical copolymers and a series of three poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)- b-polystyrene (PND-b-PS-C12) diblock polymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, in which the molecular weight of the thermoresponsive PND corona block was held constant while the polystyrene core block length was varied. The corona thickness and density of the micelles in phosphate-buffered saline (PBS, pH = 6.5) were quantified by a combination of dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Two hydrophobic model drugs, phenytoin and nilutamide, were used to examine the drug-polymer interactions in aqueous solution. Intermolecular interactions between the diblock polymer micelle corona and both drugs were revealed by 2D 1H nuclear Overhauser effect spectroscopy (NOESY). The drug-polymer “binding” strength, quantified by diffusion ordered NMR spectroscopy (DOSY), increased as corona density of the diblock polymer micelle increased for both drugs. The in vitro dissolution of the amorphous solid dispersions was systematically investigated as a function of drug type, drug loading, and the solution-state assembly of the polymers by using either a selective or nonselective spray drying solvent. Forming micelles prior to spray drying significantly enhanced phenytoin dissolution and supersaturation maintenance for the diblock polymers by storing the drug molecules in the corona.},

  doi          = {10.1021/acs.macromol.7b02297},

  journal      = {Macromolecules},

  number       = 2,

  volume       = 51,

  place        = {United States},

  year         = {Wed Jan 03 00:00:00 EST 2018},

  month        = {Wed Jan 03 00:00:00 EST 2018}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (DOE)

Publisher's Version of Record

https://doi.org/10.1021/acs.macromol.7b02297

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 30 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs
journal, October 1999

Serajuddin, Abu T. M.
Journal of Pharmaceutical Sciences, Vol. 88, Issue 10
DOI: 10.1021/js980403l

Developing early formulations: Practice and perspective
journal, August 2007

Li, Ping; Zhao, Luwei
International Journal of Pharmaceutics, Vol. 341, Issue 1-2
DOI: 10.1016/j.ijpharm.2007.05.049

Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications
journal, November 2011

Kawabata, Yohei; Wada, Koichi; Nakatani, Manabu
International Journal of Pharmaceutics, Vol. 420, Issue 1
DOI: 10.1016/j.ijpharm.2011.08.032

The use of amorphous solid dispersions: A formulation strategy to overcome poor solubility and dissolution rate
journal, June 2012

Van den Mooter, Guy
Drug Discovery Today: Technologies, Vol. 9, Issue 2
DOI: 10.1016/j.ddtec.2011.10.002

Detection of Pharmaceutical Drug Crystallites in Solid Dispersions by Transmission Electron Microscopy
journal, February 2015

Ricarte, Ralm G.; Lodge, Timothy P.; Hillmyer, Marc A.
Molecular Pharmaceutics, Vol. 12, Issue 3
DOI: 10.1021/mp500682x

Solubility Advantage of Amorphous Drugs and Pharmaceutical Cocrystals
journal, July 2011

Babu, N. Jagadeesh; Nangia, Ashwini
Crystal Growth & Design, Vol. 11, Issue 7
DOI: 10.1021/cg200492w

Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: Polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs
journal, April 2014

Sarode, Ashish L.; Wang, Peng; Obara, Sakae
European Journal of Pharmaceutics and Biopharmaceutics, Vol. 86, Issue 3
DOI: 10.1016/j.ejpb.2013.10.005

Supersaturation–Nucleation Behavior of Poorly Soluble Drugs and its Impact on the Oral Absorption of Drugs in Thermodynamically High-Energy Forms
journal, January 2012

Ozaki, Shunsuke; Minamisono, Takuma; Yamashita, Taro
Journal of Pharmaceutical Sciences, Vol. 101, Issue 1
DOI: 10.1002/jps.22760

Strategies to Address Low Drug Solubility in Discovery and Development
journal, January 2013

Williams, Hywel D.; Trevaskis, Natalie L.; Charman, Susan A.
Pharmacological Reviews, Vol. 65, Issue 1
DOI: 10.1124/pr.112.005660

Utility of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) for Initiation and Maintenance of Drug Supersaturation in the GI Milieu
journal, March 2009

Curatolo, William; Nightingale, James A.; Herbig, Scott M.
Pharmaceutical Research, Vol. 26, Issue 6
DOI: 10.1007/s11095-009-9852-z

Solubility Advantage of Amorphous Pharmaceuticals, Part 3: Is Maximum Solubility Advantage Experimentally Attainable and Sustainable?
journal, October 2011

Murdande, Sharad B.; Pikal, Michael J.; Shanker, Ravi M.
Journal of Pharmaceutical Sciences, Vol. 100, Issue 10
DOI: 10.1002/jps.22643

Deconstructing HPMCAS: Excipient Design to Tailor Polymer–Drug Interactions for Oral Drug Delivery
journal, September 2015

Ting, Jeffrey M.; Navale, Tushar S.; Jones, Seamus D.
ACS Biomaterials Science & Engineering, Vol. 1, Issue 10
DOI: 10.1021/acsbiomaterials.5b00234

Advanced drug delivery devices via self-assembly of amphiphilic block copolymers
journal, December 2012

Rösler, Annette; Vandermeulen, Guido W. M.; Klok, Harm-Anton
Advanced Drug Delivery Reviews, Vol. 64
DOI: 10.1016/j.addr.2012.09.026

Block copolymer micelles for drug delivery: design, characterization and biological significance
journal, March 2001

Kataoka, Kazunori; Harada, Atsushi; Nagasaki, Yukio
Advanced Drug Delivery Reviews, Vol. 47, Issue 1
DOI: 10.1016/S0169-409X(00)00124-1

Physical chemistry of supersaturated solutions and implications for oral absorption
journal, June 2016

Taylor, Lynne S.; Zhang, Geoff G. Z.
Advanced Drug Delivery Reviews, Vol. 101
DOI: 10.1016/j.addr.2016.03.006

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
journal, December 2012

Lipinski, Christopher A.; Lombardo, Franco; Dominy, Beryl W.
Advanced Drug Delivery Reviews, Vol. 64
DOI: 10.1016/j.addr.2012.09.019

Stimuli-responsive polymers and their applications in drug delivery
journal, March 2009

Bawa, Priya; Pillay, Viness; Choonara, Yahya E.
Biomedical Materials, Vol. 4, Issue 2
DOI: 10.1088/1748-6041/4/2/022001

Future perspectives and recent advances in stimuli-responsive materials
journal, January 2010

Roy, Debashish; Cambre, Jennifer N.; Sumerlin, Brent S.
Progress in Polymer Science, Vol. 35, Issue 1-2
DOI: 10.1016/j.progpolymsci.2009.10.008

Enhanced Performance of Blended Polymer Excipients in Delivering a Hydrophobic Drug through the Synergistic Action of Micelles and HPMCAS
journal, March 2017

Li, Ziang; Johnson, Lindsay M.; Ricarte, Ralm G.
Langmuir, Vol. 33, Issue 11
DOI: 10.1021/acs.langmuir.7b00325

Impact of Polymer Excipient Molar Mass and End Groups on Hydrophobic Drug Solubility Enhancement
journal, January 2017

Johnson, Lindsay M.; Li, Ziang; LaBelle, Andrew J.
Macromolecules, Vol. 50, Issue 3
DOI: 10.1021/acs.macromol.6b02474

Solution-State Polymer Assemblies Influence BCS Class II Drug Dissolution and Supersaturation Maintenance
journal, January 2014

Dalsin, Molly C.; Tale, Swapnil; Reineke, Theresa M.
Biomacromolecules, Vol. 15, Issue 2
DOI: 10.1021/bm401431t

Micellization and Micellar Aggregation of Poly(ethylene- alt -propylene)- b -poly(ethylene oxide)- b -poly( N -isopropylacrylamide) Triblock Terpolymers in Water
journal, March 2011

Zhou, Can; Hillmyer, Marc A.; Lodge, Timothy P.
Macromolecules, Vol. 44, Issue 6
DOI: 10.1021/ma102786q

Self-Assembly of Hydrophilic Homopolymers: A Matter of RAFT End Groups
journal, June 2011

Du, Jianzhong; Willcock, Helen; Patterson, Joseph P.
Small, Vol. 7, Issue 14
DOI: 10.1002/smll.201100382

Growth mechanism and morphology of phenytoin and their relationship with crystallographic structure
journal, August 1993

Zipp, G. L.; Rodriguez-Hornedo, N.
Journal of Physics D: Applied Physics, Vol. 26, Issue 8B
DOI: 10.1088/0022-3727/26/8B/007

Crystallization Tendency of Active Pharmaceutical Ingredients Following Rapid Solvent Evaporation—Classification and Comparison with Crystallization Tendency from Under cooled Melts
journal, September 2010

Van Eerdenbrugh, Bernard; Baird, Jared A.; Taylor, Lynne S.
Journal of Pharmaceutical Sciences, Vol. 99, Issue 9
DOI: 10.1002/jps.22214

Functional Polymers from Novel Carboxyl-Terminated Trithiocarbonates as Highly Efficient RAFT Agents
journal, August 2002

Lai, John T.; Filla, Debby; Shea, Ronald
Macromolecules, Vol. 35, Issue 18
DOI: 10.1021/ma020362m

Living Free-Radical Polymerization by Reversible Addition−Fragmentation Chain Transfer: The RAFT Process
journal, August 1998

Chiefari, John; Chong, Y. K. (Bill); Ercole, Frances
Macromolecules, Vol. 31, Issue 16
DOI: 10.1021/ma9804951

Living Radical Polymerization by the RAFT Process - A Second Update
journal, January 2009

Moad, Graeme; Rizzardo, Ezio; Thang, San H.
Australian Journal of Chemistry, Vol. 62, Issue 11
DOI: 10.1071/CH09311

pH- and Ionic-Strength-Induced Contraction of Polybasic Micelles in Buffered Aqueous Solutions
journal, April 2015

Laaser, Jennifer E.; Jiang, Yaming; Sprouse, Dustin
Macromolecules, Vol. 48, Issue 8
DOI: 10.1021/acs.macromol.5b00360

Light-scattering studies of poly(N-isopropylacrylamide) in tetrahydrofuran and aqueous solution
journal, March 1995

Zhou, Shuiqin; Fan, Shiyan; Au-yeung, Steve C. F.
Polymer, Vol. 36, Issue 7
DOI: 10.1016/0032-3861(95)95910-S

Association of Block Copolymer in Nonselective Solvent
journal, June 2009

Ke, Fuyou; Mo, Xiulei; Yang, Runmiao
Macromolecules, Vol. 42, Issue 14
DOI: 10.1021/ma900740b

Regularized Positive Exponential Sum (REPES) Program - A Way of Inverting Laplace Transform Data Obtained by Dynamic Light Scattering
journal, January 1995

Jakeš, Jaromír
Collection of Czechoslovak Chemical Communications, Vol. 60, Issue 11
DOI: 10.1135/cccc19951781

Water Suppression That Works. Excitation Sculpting Using Arbitrary Wave-Forms and Pulsed-Field Gradients
journal, February 1995

Hwang, T. L.; Shaka, A. J.
Journal of Magnetic Resonance, Series A, Vol. 112, Issue 2
DOI: 10.1006/jmra.1995.1047

Hydroxypropyl Methylcellulose Acetate Succinate-Based Spray-Dried Dispersions: An Overview
journal, November 2008

Friesen, Dwayne T.; Shanker, Ravi; Crew, Marshall
Molecular Pharmaceutics, Vol. 5, Issue 6
DOI: 10.1021/mp8000793

Molecular-weight Determination by Light Scattering.
journal, January 1947

Debye, P.
The Journal of Physical and Colloid Chemistry, Vol. 51, Issue 1
DOI: 10.1021/j150451a002

On the effect of branching and polydispersity on the angular distribution of the light scattered by gaussian coils
journal, November 1953

Benoit, H.
Journal of Polymer Science, Vol. 11, Issue 5
DOI: 10.1002/pol.1953.120110512

Form factors of block copolymer micelles with spherical, ellipsoidal and cylindrical cores
journal, June 2000

Pedersen, Jan Skov
Journal of Applied Crystallography, Vol. 33, Issue 3
DOI: 10.1107/S0021889899012248

Polymer-probe interactions in forced Rayleigh scattering measurements of probe diffusion in poly(vinyl acetate) solutions
journal, October 1987

Lee, J. A.; Lodge, T. P.
The Journal of Physical Chemistry, Vol. 91, Issue 22
DOI: 10.1021/j100306a010

Permeability of Rubbery and Glassy Membranes of Ionic Liquid Filled Polymersome Nanoreactors in Water
journal, November 2015

So, Soonyong; Yao, Letitia J.; Lodge, Timothy P.
The Journal of Physical Chemistry B, Vol. 119, Issue 48
DOI: 10.1021/acs.jpcb.5b08425

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers
journal, October 2017

Zhang, Wenjia; Haman, Karen J.; Metzger, Joseph M.
Langmuir, Vol. 33, Issue 44
DOI: 10.1021/acs.langmuir.7b02279

High-Throughput Excipient Discovery Enables Oral Delivery of Poorly Soluble Pharmaceuticals
journal, October 2016

Ting, Jeffrey M.; Tale, Swapnil; Purchel, Anatolii A.
ACS Central Science, Vol. 2, Issue 10
DOI: 10.1021/acscentsci.6b00268

Direct Observation of Nanostructures during Aqueous Dissolution of Polymer/Drug Particles
journal, April 2017

Ricarte, Ralm G.; Li, Ziang; Johnson, Lindsay M.
Macromolecules, Vol. 50, Issue 8
DOI: 10.1021/acs.macromol.7b00372

Thermodynamic Driving Force in Nucleation and Growth Processes
journal, November 1958

Hoffman, John D.
The Journal of Chemical Physics, Vol. 29, Issue 5
DOI: 10.1063/1.1744688

Role of Molecular Interactions for Synergistic Precipitation Inhibition of Poorly Soluble Drug in Supersaturated Drug–Polymer–Polymer Ternary Solution
journal, January 2016

Prasad, Dev; Chauhan, Harsh; Atef, Eman
Molecular Pharmaceutics, Vol. 13, Issue 3
DOI: 10.1021/acs.molpharmaceut.5b00655

An Investigation and Quantitative Assessment of Particle Shape in Milk Powders from a Laboratory-Scale Spray Dryer
journal, December 2006

Langrish, T. A. G.; Marquez, N.; Kota, K.
Drying Technology, Vol. 24, Issue 12
DOI: 10.1080/07373930601031133

Pharmaceutical Particle Engineering via Spray Drying
journal, November 2007

Vehring, Reinhard
Pharmaceutical Research, Vol. 25, Issue 5
DOI: 10.1007/s11095-007-9475-1

The Rate Of Solution Of Solid Substances In Their Own Solutions
journal, December 1897

Noyes, Arthur A.; Whitney, Willis R.
Journal of the American Chemical Society, Vol. 19, Issue 12, p. 930-934
DOI: 10.1021/ja02086a003

Thermo- and pH-responsive polymers in drug delivery☆
journal, December 2006

Schmaljohann, D.
Advanced Drug Delivery Reviews, Vol. 58, Issue 15
DOI: 10.1016/j.addr.2006.09.020

Blending block copolymer micelles in solution; obstacles of blending
journal, January 2016

Wright, Daniel B.; Patterson, Joseph P.; Gianneschi, Nathan C.
Polymer Chemistry, Vol. 7, Issue 8
DOI: 10.1039/C5PY02006A

pH-Responsive Vesicles Based on a Hydrolytically Self-Cross-Linkable Copolymer
journal, September 2005

Du, Jianzhong; Armes, Steven P.
Journal of the American Chemical Society, Vol. 127, Issue 37
DOI: 10.1021/ja054755n

Drug targeting using thermally responsive polymers and local hyperthermia
journal, July 2001

Meyer, D. E.; Shin, B. C.; Kong, G. A.
Journal of Controlled Release, Vol. 74, Issue 1-3
DOI: 10.1016/S0168-3659(01)00319-4

Biocompatibility and Fatigue Properties of Polystyrene−Polyisobutylene−Polystyrene, an Emerging Thermoplastic Elastomeric Biomaterial
journal, March 2006

El Fray, Miroslawa; Prowans, Piotr; Puskas, Judit E.
Biomacromolecules, Vol. 7, Issue 3
DOI: 10.1021/bm050971c

Biocompatibility, uptake and endocytosis pathways of polystyrene nanoparticles in primary human renal epithelial cells
journal, January 2015

Monti, Daria Maria; Guarnieri, Daniela; Napolitano, Giuliana
Journal of Biotechnology, Vol. 193
DOI: 10.1016/j.jbiotec.2014.11.004

Influence of Additives on the Properties of Nanodroplets Formed in Highly Supersaturated Aqueous Solutions of Ritonavir
journal, July 2013

Ilevbare, Grace A.; Liu, Haoyu; Pereira, Junia
Molecular Pharmaceutics, Vol. 10, Issue 9
DOI: 10.1021/mp400228x

Works referencing / citing this record:

Tuning PNIPAm self-assembly and thermoresponse: roles of hydrophobic end-groups and hydrophilic comonomer
journal, January 2019

Ohnsorg, Monica L.; Ting, Jeffrey M.; Jones, Seamus D.
Polymer Chemistry, Vol. 10, Issue 25
DOI: 10.1039/c9py00180h

Gastroretentive floating matrix tablets of cephradine based on psyllium husk
journal, September 2019

Sher, Muhammad; Basharat, Bushra; Hassan, Faiza
Bioinspired, Biomimetic and Nanobiomaterials, Vol. 8, Issue 3
DOI: 10.1680/jbibn.18.00049

Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine: Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine
journal, September 2018

Karmakar, Puja Das; Seesala, Venkata Sundeep; Pal, Aniruddha
Journal of Polymer Science Part A: Polymer Chemistry, Vol. 56, Issue 20
DOI: 10.1002/pola.29210

Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
journal, November 2019

Johnson, Lindsay M.; Hillmyer, Marc A.
ACS Omega, Vol. 4, Issue 21
DOI: 10.1021/acsomega.9b02383

Similar Records in DOE PAGES and OSTI.GOV collections:

Polymer Nanogels as Reservoirs To Inhibit Hydrophobic Drug Crystallization

Journal Article Li, Ziang ; Van Zee, Nicholas J. ; Bates, Frank S. ; ... - ACS Nano

Herein the effects of cross-link density and composition on the loading and in vitro dissolution of the drug phenytoin as amorphous solid dispersions in emulsion polymerized poly(N-isopropylacrylamide) (PNIPAm) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) nanogels were investigated near the lower critical solution temperature (LCST). Nanogel size and particle density in phosphate buffered saline were quantified by dynamic light scattering (DLS) and viscometry experiments, while drug–nanogel interactions were revealed by cross peaks in aqueous-state nuclear Overhauser effect spectroscopy measurements. Spray-dried dispersions (SDDs) of drug-loaded PNIPAm nanogel particles (R ≈ 43 nm) were directly visualized by cryogenic transmission electron microscopy and further quantified by small-angle X-raymore »« less
Cited by 25
https://doi.org/10.1021/acsnano.8b06393

Full Text Available
Thermoresponsive magnetic micelles for simultaneous magnetic hyperthermia and drug delivery.

Conference Kim, D -H ; Rozhkova, E A ; Rajh, T ; ...

Hyperthermia has been shown to be a potentially effective therapeutic modality in cancer treatment as it intensifies the efficacy of chemotherapy. The hyperthermia has a good synergic effect with chemotherapy. Their sensitivity to chemotherapy after hyperthermia treatment is increased. Therefore, a simultaneous hyperthermia and chemotherapy can be a new approach for cancer treatment. Multifunctional magnetic nanoparticles with thermoresponsive polymer allowed the simultaneous cancer therapy because the functions of thermo triggered drug release and heating for hyperthermia can be performed simultaneously by applied magnetic field. In our study, magnetic nanoparticles loaded thermoresponsive micelles were synthesized for the simultaneous magnetic hyperthermia andmore »« less
Poly(methyl methacrylate)-block-poly(n-butyl methacrylate) Diblock Copolymer Micelles in an Ionic Liquid: Scaling of Core and Corona Size with Core Block Length

Journal Article Ma, Yuanchi ; Lodge, Timothy P. - Macromolecules

Here, the structure of poly(methyl methacrylate)-block-poly(n-butyl methacrylate) (PMMA-b-PnBMA) micelles in the room temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]), a selective solvent for the PMMA block, has been studied using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). A series of seven PMMA-b-PnBMA diblock copolymers were prepared by reversible addition–fragmentation chain-transfer (RAFT) polymerization, in which the degree of polymerization of the PMMA block was kept constant while the PnBMA block length was varied. All the polymers formed spherical micelles at ambient temperature in dilute solution; their hydrodynamic radius (R_h) and core radius (R_c) were obtained by DLS and SAXS, respectively.more »« less
Cited by 21
https://doi.org/10.1021/acs.macromol.6b00315

Full Text Available
A Stepwise "Micellization-Crystallization" Route to Oblate Ellipsoidal, Cylindrical, and Bilayer Micelles with Polyethylene Cores in Water

Journal Article Yin, Ligeng ; Lodge, Timothy P ; Hillmyer, Marc A - Macromolecules

Micellar polymorphism from block copolymers has been well documented, but most attention has focused on noncrystalline hydrophobic systems. We have investigated the micellization in water of model diblock copolymers with semicrystalline polyethylene (PE) as the core-forming component. Poly(N,N-dimethylacrylamide)–polyethylene (AE) diblock copolymers were synthesized by a combination of anionic and RAFT polymerizations. The bulk nanostructures were probed by small-angle X-ray scattering (SAXS) and AE diblock copolymers were found to be moderately segregated at 140 °C. Dispersions of AE amphiphiles in water were prepared by direct dissolution at 120 °C (i.e., above the melting transition of PE) followed by cooling to 25more »« less
https://doi.org/10.1021/ma302069s
Synthesis of hybrid gold/iron oxide nanoparticles in block copolymer micelles for imaging, drug delivery and magnetic hyperthermia.

Journal Article Kim, D -H ; Rozhkova, E A ; Rajh, T ; ... - IEEE Trans. Magn.

In our study, hybrid gold/iron oxide loaded thermoresponsive micelles were synthesized for combined hyperthermia and chemotherapy, and optical imaging. Polymeric micelles made of amphiphilic block copolymer of poly(N-isopropylacrylamide-co-acrylamide)-block-poly({var_epsilon}-caprolactone) were conjugated with gold/iron oxide particles which are self-assembled at the hydrophobic polymer core. Thermal sensitivity and magnetic and optical properties of the hybrid gold/iron oxide micelles were investigated for the combined therapy and optical imaging.
https://doi.org/10.1109/TMAG.2009.2024000

Similar Records

Title: Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir

Abstract

Citation Formats

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs journal, October 1999

Developing early formulations: Practice and perspective journal, August 2007

Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications journal, November 2011

The use of amorphous solid dispersions: A formulation strategy to overcome poor solubility and dissolution rate journal, June 2012

Detection of Pharmaceutical Drug Crystallites in Solid Dispersions by Transmission Electron Microscopy journal, February 2015

Solubility Advantage of Amorphous Drugs and Pharmaceutical Cocrystals journal, July 2011

Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: Polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs journal, April 2014

Supersaturation–Nucleation Behavior of Poorly Soluble Drugs and its Impact on the Oral Absorption of Drugs in Thermodynamically High-Energy Forms journal, January 2012

Strategies to Address Low Drug Solubility in Discovery and Development journal, January 2013

Utility of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) for Initiation and Maintenance of Drug Supersaturation in the GI Milieu journal, March 2009

Solubility Advantage of Amorphous Pharmaceuticals, Part 3: Is Maximum Solubility Advantage Experimentally Attainable and Sustainable? journal, October 2011

Deconstructing HPMCAS: Excipient Design to Tailor Polymer–Drug Interactions for Oral Drug Delivery journal, September 2015

Advanced drug delivery devices via self-assembly of amphiphilic block copolymers journal, December 2012

Block copolymer micelles for drug delivery: design, characterization and biological significance journal, March 2001

Physical chemistry of supersaturated solutions and implications for oral absorption journal, June 2016

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings journal, December 2012

Stimuli-responsive polymers and their applications in drug delivery journal, March 2009

Future perspectives and recent advances in stimuli-responsive materials journal, January 2010

Enhanced Performance of Blended Polymer Excipients in Delivering a Hydrophobic Drug through the Synergistic Action of Micelles and HPMCAS journal, March 2017

Impact of Polymer Excipient Molar Mass and End Groups on Hydrophobic Drug Solubility Enhancement journal, January 2017

Solution-State Polymer Assemblies Influence BCS Class II Drug Dissolution and Supersaturation Maintenance journal, January 2014

Micellization and Micellar Aggregation of Poly(ethylene- alt -propylene)- b -poly(ethylene oxide)- b -poly( N -isopropylacrylamide) Triblock Terpolymers in Water journal, March 2011

Self-Assembly of Hydrophilic Homopolymers: A Matter of RAFT End Groups journal, June 2011

Growth mechanism and morphology of phenytoin and their relationship with crystallographic structure journal, August 1993

Crystallization Tendency of Active Pharmaceutical Ingredients Following Rapid Solvent Evaporation—Classification and Comparison with Crystallization Tendency from Under cooled Melts journal, September 2010

Functional Polymers from Novel Carboxyl-Terminated Trithiocarbonates as Highly Efficient RAFT Agents journal, August 2002

Living Free-Radical Polymerization by Reversible Addition−Fragmentation Chain Transfer: The RAFT Process journal, August 1998

Living Radical Polymerization by the RAFT Process - A Second Update journal, January 2009

pH- and Ionic-Strength-Induced Contraction of Polybasic Micelles in Buffered Aqueous Solutions journal, April 2015

Light-scattering studies of poly(N-isopropylacrylamide) in tetrahydrofuran and aqueous solution journal, March 1995

Association of Block Copolymer in Nonselective Solvent journal, June 2009

Regularized Positive Exponential Sum (REPES) Program - A Way of Inverting Laplace Transform Data Obtained by Dynamic Light Scattering journal, January 1995

Water Suppression That Works. Excitation Sculpting Using Arbitrary Wave-Forms and Pulsed-Field Gradients journal, February 1995

Hydroxypropyl Methylcellulose Acetate Succinate-Based Spray-Dried Dispersions: An Overview journal, November 2008

Molecular-weight Determination by Light Scattering. journal, January 1947

On the effect of branching and polydispersity on the angular distribution of the light scattered by gaussian coils journal, November 1953

Form factors of block copolymer micelles with spherical, ellipsoidal and cylindrical cores journal, June 2000

Polymer-probe interactions in forced Rayleigh scattering measurements of probe diffusion in poly(vinyl acetate) solutions journal, October 1987

Permeability of Rubbery and Glassy Membranes of Ionic Liquid Filled Polymersome Nanoreactors in Water journal, November 2015

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers journal, October 2017

High-Throughput Excipient Discovery Enables Oral Delivery of Poorly Soluble Pharmaceuticals journal, October 2016

Direct Observation of Nanostructures during Aqueous Dissolution of Polymer/Drug Particles journal, April 2017

Thermodynamic Driving Force in Nucleation and Growth Processes journal, November 1958

Role of Molecular Interactions for Synergistic Precipitation Inhibition of Poorly Soluble Drug in Supersaturated Drug–Polymer–Polymer Ternary Solution journal, January 2016

An Investigation and Quantitative Assessment of Particle Shape in Milk Powders from a Laboratory-Scale Spray Dryer journal, December 2006

Pharmaceutical Particle Engineering via Spray Drying journal, November 2007

The Rate Of Solution Of Solid Substances In Their Own Solutions journal, December 1897

Thermo- and pH-responsive polymers in drug delivery☆ journal, December 2006

Blending block copolymer micelles in solution; obstacles of blending journal, January 2016

pH-Responsive Vesicles Based on a Hydrolytically Self-Cross-Linkable Copolymer journal, September 2005

Drug targeting using thermally responsive polymers and local hyperthermia journal, July 2001

Biocompatibility and Fatigue Properties of Polystyrene−Polyisobutylene−Polystyrene, an Emerging Thermoplastic Elastomeric Biomaterial journal, March 2006

Biocompatibility, uptake and endocytosis pathways of polystyrene nanoparticles in primary human renal epithelial cells journal, January 2015

Influence of Additives on the Properties of Nanodroplets Formed in Highly Supersaturated Aqueous Solutions of Ritonavir journal, July 2013

Tuning PNIPAm self-assembly and thermoresponse: roles of hydrophobic end-groups and hydrophilic comonomer journal, January 2019

Gastroretentive floating matrix tablets of cephradine based on psyllium husk journal, September 2019

Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine: Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine journal, September 2018

Critical Excipient Properties for the Dissolution Enhancement of Phenytoin journal, November 2019

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs
journal, October 1999

Developing early formulations: Practice and perspective
journal, August 2007

Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications
journal, November 2011

The use of amorphous solid dispersions: A formulation strategy to overcome poor solubility and dissolution rate
journal, June 2012

Detection of Pharmaceutical Drug Crystallites in Solid Dispersions by Transmission Electron Microscopy
journal, February 2015

Solubility Advantage of Amorphous Drugs and Pharmaceutical Cocrystals
journal, July 2011

Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: Polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs
journal, April 2014

Supersaturation–Nucleation Behavior of Poorly Soluble Drugs and its Impact on the Oral Absorption of Drugs in Thermodynamically High-Energy Forms
journal, January 2012

Strategies to Address Low Drug Solubility in Discovery and Development
journal, January 2013

Utility of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) for Initiation and Maintenance of Drug Supersaturation in the GI Milieu
journal, March 2009

Solubility Advantage of Amorphous Pharmaceuticals, Part 3: Is Maximum Solubility Advantage Experimentally Attainable and Sustainable?
journal, October 2011

Deconstructing HPMCAS: Excipient Design to Tailor Polymer–Drug Interactions for Oral Drug Delivery
journal, September 2015

Advanced drug delivery devices via self-assembly of amphiphilic block copolymers
journal, December 2012

Block copolymer micelles for drug delivery: design, characterization and biological significance
journal, March 2001

Physical chemistry of supersaturated solutions and implications for oral absorption
journal, June 2016

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
journal, December 2012

Stimuli-responsive polymers and their applications in drug delivery
journal, March 2009

Future perspectives and recent advances in stimuli-responsive materials
journal, January 2010

Enhanced Performance of Blended Polymer Excipients in Delivering a Hydrophobic Drug through the Synergistic Action of Micelles and HPMCAS
journal, March 2017

Impact of Polymer Excipient Molar Mass and End Groups on Hydrophobic Drug Solubility Enhancement
journal, January 2017

Solution-State Polymer Assemblies Influence BCS Class II Drug Dissolution and Supersaturation Maintenance
journal, January 2014

Micellization and Micellar Aggregation of Poly(ethylene- alt -propylene)- b -poly(ethylene oxide)- b -poly( N -isopropylacrylamide) Triblock Terpolymers in Water
journal, March 2011

Self-Assembly of Hydrophilic Homopolymers: A Matter of RAFT End Groups
journal, June 2011

Growth mechanism and morphology of phenytoin and their relationship with crystallographic structure
journal, August 1993

Crystallization Tendency of Active Pharmaceutical Ingredients Following Rapid Solvent Evaporation—Classification and Comparison with Crystallization Tendency from Under cooled Melts
journal, September 2010

Functional Polymers from Novel Carboxyl-Terminated Trithiocarbonates as Highly Efficient RAFT Agents
journal, August 2002

Living Free-Radical Polymerization by Reversible Addition−Fragmentation Chain Transfer: The RAFT Process
journal, August 1998

Living Radical Polymerization by the RAFT Process - A Second Update
journal, January 2009

pH- and Ionic-Strength-Induced Contraction of Polybasic Micelles in Buffered Aqueous Solutions
journal, April 2015

Light-scattering studies of poly(N-isopropylacrylamide) in tetrahydrofuran and aqueous solution
journal, March 1995

Association of Block Copolymer in Nonselective Solvent
journal, June 2009

Regularized Positive Exponential Sum (REPES) Program - A Way of Inverting Laplace Transform Data Obtained by Dynamic Light Scattering
journal, January 1995

Water Suppression That Works. Excitation Sculpting Using Arbitrary Wave-Forms and Pulsed-Field Gradients
journal, February 1995

Hydroxypropyl Methylcellulose Acetate Succinate-Based Spray-Dried Dispersions: An Overview
journal, November 2008

Molecular-weight Determination by Light Scattering.
journal, January 1947

On the effect of branching and polydispersity on the angular distribution of the light scattered by gaussian coils
journal, November 1953

Form factors of block copolymer micelles with spherical, ellipsoidal and cylindrical cores
journal, June 2000

Polymer-probe interactions in forced Rayleigh scattering measurements of probe diffusion in poly(vinyl acetate) solutions
journal, October 1987

Permeability of Rubbery and Glassy Membranes of Ionic Liquid Filled Polymersome Nanoreactors in Water
journal, November 2015

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers
journal, October 2017

High-Throughput Excipient Discovery Enables Oral Delivery of Poorly Soluble Pharmaceuticals
journal, October 2016

Direct Observation of Nanostructures during Aqueous Dissolution of Polymer/Drug Particles
journal, April 2017

Thermodynamic Driving Force in Nucleation and Growth Processes
journal, November 1958

Role of Molecular Interactions for Synergistic Precipitation Inhibition of Poorly Soluble Drug in Supersaturated Drug–Polymer–Polymer Ternary Solution
journal, January 2016

An Investigation and Quantitative Assessment of Particle Shape in Milk Powders from a Laboratory-Scale Spray Dryer
journal, December 2006

Pharmaceutical Particle Engineering via Spray Drying
journal, November 2007

The Rate Of Solution Of Solid Substances In Their Own Solutions
journal, December 1897

Thermo- and pH-responsive polymers in drug delivery☆
journal, December 2006

Blending block copolymer micelles in solution; obstacles of blending
journal, January 2016

pH-Responsive Vesicles Based on a Hydrolytically Self-Cross-Linkable Copolymer
journal, September 2005

Drug targeting using thermally responsive polymers and local hyperthermia
journal, July 2001

Biocompatibility and Fatigue Properties of Polystyrene−Polyisobutylene−Polystyrene, an Emerging Thermoplastic Elastomeric Biomaterial
journal, March 2006

Biocompatibility, uptake and endocytosis pathways of polystyrene nanoparticles in primary human renal epithelial cells
journal, January 2015

Influence of Additives on the Properties of Nanodroplets Formed in Highly Supersaturated Aqueous Solutions of Ritonavir
journal, July 2013

Tuning PNIPAm self-assembly and thermoresponse: roles of hydrophobic end-groups and hydrophilic comonomer
journal, January 2019

Gastroretentive floating matrix tablets of cephradine based on psyllium husk
journal, September 2019

Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine: Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine
journal, September 2018

Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
journal, November 2019