Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity

Si Dong; Sheng Ma; Zhi-Lin Liu; Li-Li Ma; Yu Zhang; Zhao-Hui Tang; Ming-Xiao Deng; Wan-Tong Song

doi:10.1007/s10118-021-2547-6

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Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity

ARTICLE | Updated：2021-05-13

- Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity
- Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity
- Chinese Journal of Polymer Science 2021年39卷第7期页码：865-873
- Affiliations：
  
  a.College of Chemistry, Northeast Normal University, Changchun 130024, China
  b.Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- Author bio：
  
  dengmx330@nenu.edu.cn (M.X.D.)
  wtsong@ciac.ac.cn (W.T.S.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 51673185, 51973215, 51673189, 51829302, 52003268 and 52025035), as well as the support from the Youth Innovation Promotion Association of Chinese Academy of Sciences (No. 2020232).
- DOI：10.1007/s10118-021-2547-6
  中图分类号：
- 收稿：2020-11-14，
  
  修回：2020-12-22，
  
  录用：2021-1-4，
  
  网络首发：2021-05-13，
  
  纸质出版：2021-05-14
- Accepted：
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Dong, S.; Ma, S.; Liu, Z. L.; Ma, L. L.; Zhang, Y.; Tang, Z. H.; Deng, M. X.; Song, W. T. Functional amphiphilic poly(2-oxazoline) block copolymers as drug carriers: the relationship between structure and drug loading capacity. Chinese J. Polym. Sci. 2021, 39, 865–873

Si Dong, Sheng Ma, Zhi-Lin Liu, et al. Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity[J]. Chinese Journal of Polymer Science, 2021, 39(7): 865-873.
Dong, S.; Ma, S.; Liu, Z. L.; Ma, L. L.; Zhang, Y.; Tang, Z. H.; Deng, M. X.; Song, W. T. Functional amphiphilic poly(2-oxazoline) block copolymers as drug carriers: the relationship between structure and drug loading capacity. Chinese J. Polym. Sci. 2021, 39, 865–873 DOI： 10.1007/s10118-021-2547-6.

Si Dong, Sheng Ma, Zhi-Lin Liu, et al. Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity[J]. Chinese Journal of Polymer Science, 2021, 39(7): 865-873. DOI： 10.1007/s10118-021-2547-6.

摘要

Abstract

Poly(2-oxazoline) (POx) is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto- and hemo-compatibility

and is promising to be used as drug carriers. However

the drug loading capacity (DLC) of POx for many drugs is still low except several hydrophobic ones including paclitaxel (PTX). Herein

we prepared a series of amphiphilic POx block copolymers with various functional groups

and investigated the relationship between functional structures and the DLC. Functional POxs with benzyl

carboxyl

and amino groups in the side-chain were synthesized based on a poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline-

-2-butenyl-2-oxazoline) (PMeOx-P(

BuOx-

-ButenOx)

PMBEOx) precursor

followed by click reaction between vinyl and the 2-phenylethanethiol

thioglycolic acid and cysteamine. Using thin-film hydration method

eight commonly used drugs with various characteristics were encapsulated within these functional POx polymers. We found that amine-containing drugs were more easily encapsulated by POx with carboxyl groups

while amine functionalities in POx enhanced the loading capacity of drugs with carboxyl groups. In addition

interactions resulted in enhanced DLC of most drugs

except several hydrophobic drugs with aromatic to total carbon ratios less than 0.5. In general

we could successfully encapsulate all the selected drugs with a DLC% over 10% using properly selected functional POxs. The above results confirm that the DLC of polymeric carriers can be adjusted by modifying the functional groups

and the prepared series of functional POxs provide an option for various drug loadings.

关键词

Keywords

references

Lasic, D. D. . Doxorubicin in sterically stabilized liposomes . Nature , 1996 . 380 561 - 562 . DOI: 10.1038/380561a0 http://doi.org/10.1038/380561a0 .

Couvreur, P.; Puisieux, F. . Nanopartiles and microparticles for the delivery of polypeptides and proteins . Adv. Drug Deliv. Rev. , 1993 . 10 141 - 162 . DOI: 10.1016/0169-409X(93)90046-7 http://doi.org/10.1016/0169-409X(93)90046-7 .

Akiyoshi, K.; Kobayashi, S.; Shichibe, S.; Mix, D.; Baudys, M.; Kim, S. W.; Sunamoto, J. . Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin . J. Control. Rel. , 1998 . 54 313 - 320 . DOI: 10.1016/S0168-3659(98)00017-0 http://doi.org/10.1016/S0168-3659(98)00017-0 .

Allemann, E.; Gurny, R.; Doelker, E. . Drug-loaded nanoparticles - preparation methods and drug targeting issues . Eur. J. Pharm. Biopharm. , 1993 . 39 173 - 191 . .

Duncan, R. . Drug polymer conjugates—potential for improved chemotherapy . Anti-Cancer Drugs , 1992 . 3 175 - 210 . DOI: 10.1097/00001813-199206000-00001 http://doi.org/10.1097/00001813-199206000-00001 .

Jiang, G. B.; Geng, B. W.; Fang, Y. S.; Gao, Y. F. . Polymeric micelles as new drug carriers . Modern Chem. Ind. , 2007 . 27 69 .

Li, Y.; Kwon, G. S. . Micelle-like structures of poly(ethylene oxide)-block-poly(2-hydroxyetbyl aspartamide)-methotrexate conjugates . Colloid Surf. B-Biointerfaces , 1999 . 16 217 - 226 . DOI: 10.1016/S0927-7765(99)00072-7 http://doi.org/10.1016/S0927-7765(99)00072-7 .

Li, Y.; Kwon, G. S. . Methotrexate esters of poly(ethylene oxide)-block-poly(2-hydroxyethyl-L-aspartamide). Part I: effects of the level of methotrexate conjugation on the stability of micelles and on drug release . Pharm. Res. , 2000 . 17 607 - 611 . DOI: 10.1023/A:1007529218802 http://doi.org/10.1023/A:1007529218802 .

Gref, R.; Minamitake, Y.; Peracchia, M. T.; Trubetskoy, V.; Torchilin, V.; Langer, R. . Biodegradable long-circulating polymeric nanospheres . Science , 1994 . 263 1600 - 1603 . DOI: 10.1126/science.8128245 http://doi.org/10.1126/science.8128245 .

La, S. B.; Okano, T.; Kataoka, K. . Preparation and characterization of the micelle-forming polymeric drug indomethacin-incorporated poly(ethylene oxide)-poly( β -benzyl L-aspartate) block copolymer micelles . J. Pharm. Sci. , 1996 . 85 85 - 90 . DOI: 10.1021/js950204r http://doi.org/10.1021/js950204r .

Cao, T.; Munk, P.; Ramireddy, C.; Tuzar, Z.; Webber, S. E. . Fluorescence studies of amphiphilic poly(methacrylic acid)-block-polystyrene-block-poly(methacrylic acid) micelles . Macromolecules , 1991 . 24 6300 - 6305 . DOI: 10.1021/ma00023a036 http://doi.org/10.1021/ma00023a036 .

Kwon, G.; Naito, M.; Yokoyama, M.; Okano, T.; Sakurai, Y.; Kataoka, K. . Block copolymer micelles for drug delivery: loading and release of doxorubicin . J. Control. Rel. , 1997 . 48 195 - 201 . DOI: 10.1016/S0168-3659(97)00039-4 http://doi.org/10.1016/S0168-3659(97)00039-4 .

Kwon, G. S.; Naito, M.; Yokoyama, M.; Okano, T.; Sakurai, Y.; Kataoka, K. . Physical entrapment of adriamycin in ab block-copolymer micelles . Pharm. Res. , 1995 . 12 192 - 195 . DOI: 10.1023/A:1016266523505 http://doi.org/10.1023/A:1016266523505 .

Piskin, E.; Kaitian, X.; Denkbas, E. B.; Kucukyavuz, Z. . Novel PDLLA/PEG copolymer micelles as drug carriers . J. Biomater. Sci.-Polym. Ed. , 1995 . 7 359 - 373 . .

Ma, S.; Song, W.; Xu, Y.; Si, X.; Zhang, D.; Lv, S.; Yang, C.; Ma, L.; Tang, Z.; Chen, X. . Neutralizing tumor-promoting inflammation with polypeptide-dexamethasone conjugate for microenvironment modulation and colorectal cancer therapy . Biomaterials , 2020 . 232 .

Ma, S.; Song, W.; Xu, Y.; Si, X.; Zhang, Y.; Tang, Z.; Chen, X. . A ROS-responsive aspirin polymeric prodrug for modulation of tumor microenvironment and cancer immunotherapy . CCS Chem. , 2020 . 390 - 400 . .

Jones, M. C.; Leroux, J. C. . Polymeric micelles—a new generation of colloidal drug carriers . Eur. J. Pharm. Biopharm. , 1999 . 48 101 - 111 . DOI: 10.1016/S0939-6411(99)00039-9 http://doi.org/10.1016/S0939-6411(99)00039-9 .

Woodle, M. C.; Engbers, C. M.; Zalipsky, S. . New amphipatic polymer lipid conjugates forming long-circulating reticuloendothelial system-evading liposomes . Bioconjugate Chem. , 1994 . 5 493 - 496 . DOI: 10.1021/bc00030a001 http://doi.org/10.1021/bc00030a001 .

Bayley, D.; Sancho, M. R.; Brown, J.; Brookman, L.; Petrak, K.; Goddard, P.; Steward, A. . Soluble polymeric carriers for drug delivery. 6. preparation and biodistribution of N 5 -hydroxyethyl- l -glutamine- co - l -glutamic acid copolymers in rats . J. Bioact. Compat. Polym. , 1993 . 8 51 - 68 . DOI: 10.1177/088391159300800104 http://doi.org/10.1177/088391159300800104 .

He, Z. J.; Wan, X. M.; Schulz, A.; Bludau, H.; Dobrovolskaia, M. A.; Stern, S. T.; Montgomery, S. A.; Yuan, H.; Li, Z. B.; Alakhova, D.; Sokolsky, M.; Darr, D. B.; Perou, C. M.; Jordan, R.; Luxenhofer, R.; Kabanov, A. V. . A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity . Biomaterials , 2016 . 101 296 - 309 . DOI: 10.1016/j.biomaterials.2016.06.002 http://doi.org/10.1016/j.biomaterials.2016.06.002 .

Lorson, T.; Lubtow, M. M.; Wegener, E.; Haider, M. S.; Borova, S.; Nahm, D.; Jordan, R.; Sokolski-Papkov, M.; Kabanov, A. V.; Luxenhofer, R. . Poly(2-oxazoline)s based biomaterials: a comprehensive and critical update . Biomaterials , 2018 . 178 204 - 280 . DOI: 10.1016/j.biomaterials.2018.05.022 http://doi.org/10.1016/j.biomaterials.2018.05.022 .

Luxenhofer, R.; Schulz, A.; Roques, C.; Li, S.; Bronich, T. K.; Batrakova, E. V.; Jordan, R.; Kabanov, A. V. . Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs . Biomaterials , 2010 . 31 4972 - 4979 . DOI: 10.1016/j.biomaterials.2010.02.057 http://doi.org/10.1016/j.biomaterials.2010.02.057 .

Han, Y. C.; He, Z. J.; Schulz, A.; Bronich, T. K.; Jordan, R.; Luxenhofer, R.; Kabanov, A. V. . Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles . Mol. Pharm. , 2012 . 9 2302 - 2313 . DOI: 10.1021/mp300159u http://doi.org/10.1021/mp300159u .

Wan, X. M.; Min, Y. Z.; Bludau, H.; Keith, A.; Sheiko, S. S.; Jordan, R.; Wang, A. Z.; Sokolsky-Papkov, M.; Kabanov, A. V. . Drug combination synergy in worm-like polymeric micelles improves treatment outcome for small cell and non-small cell lung cancer . ACS Nano , 2018 . 12 2426 - 2439 . DOI: 10.1021/acsnano.7b07878 http://doi.org/10.1021/acsnano.7b07878 .

Hwang, D.; Ramsey, J. D.; Makita, N.; Sachse, C.; Jordan, R.; Sokolsky-Papkov, M.; Kabanov, A. V. . Novel poly(2-oxazoline) block copolymer with aromatic heterocyclic side chains as a drug delivery platform . J. Control. Rel. , 2019 . 307 261 - 271 . DOI: 10.1016/j.jconrel.2019.06.037 http://doi.org/10.1016/j.jconrel.2019.06.037 .

Harada, A.; Kataoka, K. . Formation of polyion complex micelles in an aqueous milieu from a pair of oppositely-charged block-copolymers with poly(ethylene glycol) segments . Macromolecules , 1995 . 28 5294 - 5299 . DOI: 10.1021/ma00119a019 http://doi.org/10.1021/ma00119a019 .

Harada, A.; Kataoka, K. . Formation of stable and monodispersive polyion complex micelles in aqueous medium from poly(L-lysine) and poly(ethylene glycol)-poly(aspartic acid) block copolymer . J. Macromol. Sci. Pure Appl. Chem. , 1997 . A34 2119 - 2133 . .

Kataoka, K.; Ishihara, A.; Harada, A.; Miyazaki, H. . Effect of the secondary structure of poly(L-lysine) segments on the micellization in aqueous milieu of poly(ethylene glycol) poly(L-lysine) block copolymer partially substituted with a hydrocinnamoyl group at the N - ε -position . Macromolecules , 1998 . 31 6071 - 6076 . DOI: 10.1021/ma971838i http://doi.org/10.1021/ma971838i .

Yokoyama, M.; Fukushima, S.; Uehara, R.; Okamoto, K.; Kataoka, K.; Sakurai, Y.; Okano, T. . Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor . J. Control. Rel. , 1998 . 50 79 - 92 . DOI: 10.1016/S0168-3659(97)00115-6 http://doi.org/10.1016/S0168-3659(97)00115-6 .

Li, Q. S.; Yang, Y.; Hong, H.; Chen, X. S. . Nanoscaled poly(L-glutamic acid)/doxorubicin-amphiphile complex as pH-responsive drug delivery system for effective treatment of nonsmall cell lung cancer . ACS Appl. Mater. Interfaces , 2013 . 5 1781 - 1792 . DOI: 10.1021/am303073u http://doi.org/10.1021/am303073u .

Lv, S.; Li, M.; Tang, Z.; Song, W.; Sun, H.; Liu, H.; Chen, X. . Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy . Acta Biomater. , 2013 . 9 9330 - 9342 . DOI: 10.1016/j.actbio.2013.08.015 http://doi.org/10.1016/j.actbio.2013.08.015 .

Shi, Y.; van Steenbergen, M. J.; Teunissen, E. A.; Novo, L.; Gradmann, S.; Baldus, M.; van Nostrum, C. F.; Hennink, W. E. . π - π Stacking increases the stability and loading capacity of thermosensitive polymeric micelles for chemotherapeutic drugs . Biomacromolecules , 2013 . 14 1826 - 1837 . DOI: 10.1021/bm400234c http://doi.org/10.1021/bm400234c .

Lv, S. X.; Wu, Y. C.; Cai, K. M.; He, H.; Li, Y. J.; Lan, M.; Chen, X. S.; Cheng, J. J.; Yin, L. C. . High drug loading and sub-quantitative loading efficiency of polymeric micelles driven by donor-receptor coordination interactions . J. Am. Chem. Soc. , 2018 . 140 1235 - 1238 . DOI: 10.1021/jacs.7b12776 http://doi.org/10.1021/jacs.7b12776 .

Hahn, L.; Luebtow, M. M.; Lorson, T.; Schmitt, F.; Appelt-Menzel, A.; Schobert, R.; Luxenhofer, R. . Investigating the influence of aromatic moieties on the formulation of hydrophobic natural products and drugs in poly(2-oxazoline)-based amphiphiles . Biomacromolecules , 2018 . 19 3119 - 3128 . DOI: 10.1021/acs.biomac.8b00708 http://doi.org/10.1021/acs.biomac.8b00708 .

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