Functional Block Copolymer Micelles Based on Poly (jasmine Lactone) for Improving the Loading Efficiency of Weakly Basic Drugs

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Nov 2

PMID 36320859

Authors

Aliaa Ali

Rajendra Bhadane

Afshin Ansari Asl

Carl-Eric Wilen

Outi Salo-Ahen

Jessica M Rosenholm

Kuldeep K Bansal

Affiliations

Soon will be listed here.

Abstract

Functionalization of polymers is an attractive approach to introduce specific molecular forces that can enhance drug-polymer interaction to achieve higher drug loading when used as drug delivery systems. The novel amphiphilic block copolymer of methoxy poly(ethylene glycol) and poly(jasmine lactone) , mPEG--PJL, derived from renewable jasmine lactone provides free allyl groups on the backbone thus, allowing flexible and facile post-synthesis functionalization. In this study, mPEG--PJL and its carboxyl functionalized polymer mPEG--PJL-COOH were utilised to explore the effect of ionic interactions on the drug-polymer behaviour. Various drugs with different p values were employed to prepare drug-loaded polymeric micelles (PMs) of mPEG--PJL, mPEG--PJL-COOH and Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) a nanoprecipitation method. Electrostatic interactions between the COOH pendant on mPEG--PJL-COOH and the basic drugs were shown to influence the entrapment efficiency. Additionally, molecular dynamics (MD) simulations were employed to understand the polymer-drug interactions at the molecular level and how polymer functionalization influenced these interactions. The release kinetics of the anti-cancer drug sunitinib from mPEG--PJL and mPEG--PJL-COOH was assessed, and it demonstrated a sustainable drug release pattern, which depended on both pH and temperature. Furthermore, the cytotoxicity of sunitinib-loaded micelles on cancer cells was evaluated. The drug-loaded micelles exhibited dose-dependent toxicity. Also, haemolysis capacity of these polymers was investigated. In summary, polymer functionalization seems a promising approach to overcome challenges that hinder the application of polymer-based drug delivery systems such as low drug loading degree.

Citing Articles

Reactive Oxygen Species-Regulated Conjugates Based on Poly(jasmine) Lactone for Simultaneous Delivery of Doxorubicin and Docetaxel.

Verma J, Kumar V, Wilen C, Rosenholm J, Bansal K Pharmaceutics. 2024; 16(9).

PMID: 39339200 PMC: 11434831. DOI: 10.3390/pharmaceutics16091164.

Advancement in Solubilization Approaches: A Step towards Bioavailability Enhancement of Poorly Soluble Drugs.

Kumari L, Choudhari Y, Patel P, Gupta G, Singh D, Rosenholm J Life (Basel). 2023; 13(5).

PMID: 37240744 PMC: 10221903. DOI: 10.3390/life13051099.

References

Liu J, Lee H, Allen C . Formulation of drugs in block copolymer micelles: drug loading and release. Curr Pharm Des. 2006; 12(36):4685-701. DOI: 10.2174/138161206779026263. View

Ghosh B, Biswas S . Polymeric micelles in cancer therapy: State of the art. J Control Release. 2021; 332:127-147. DOI: 10.1016/j.jconrel.2021.02.016. View

Zheng S, Xie Y, Li Y, Li L, Tian N, Zhu W . Development of high drug-loading nanomicelles targeting steroids to the brain. Int J Nanomedicine. 2014; 9:55-66. PMC: 3872275. DOI: 10.2147/IJN.S52576. View

Shih Y, Peng C, Chiang P, Shieh M . Dual-Functional Polymeric Micelles Co-Loaded with Antineoplastic Drugs and Tyrosine Kinase Inhibitor for Combination Therapy in Colorectal Cancer. Pharmaceutics. 2022; 14(4). PMC: 9030189. DOI: 10.3390/pharmaceutics14040768. View

Kost B, Gonciarz W, Krupa A, Socka M, Rogala M, Biela T . pH-tunable nanoparticles composed of copolymers of lactide and allyl-glycidyl ether with various functionalities for the efficient delivery of anti-cancer drugs. Colloids Surf B Biointerfaces. 2021; 204:111801. DOI: 10.1016/j.colsurfb.2021.111801. View

Jhaveri A, Torchilin V . Multifunctional polymeric micelles for delivery of drugs and siRNA. Front Pharmacol. 2014; 5:77. PMC: 4007015. DOI: 10.3389/fphar.2014.00077. View

Hooshmand S, Eshaghi Z . Hydrophilic modified magnetic multi-walled carbon nanotube for dispersive solid/liquid phase microextraction of sunitinib in human samples. Anal Biochem. 2017; 542:76-83. DOI: 10.1016/j.ab.2017.11.019. View

Bachar M, Mandelbaum A, Portnaya I, Perlstein H, Even-Chen S, Barenholz Y . Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles. J Control Release. 2012; 160(2):164-71. DOI: 10.1016/j.jconrel.2012.01.004. View

Lee J, Cho E, Cho K . Incorporation and release behavior of hydrophobic drug in functionalized poly(D,L-lactide)-block-poly(ethylene oxide) micelles. J Control Release. 2004; 94(2-3):323-35. DOI: 10.1016/j.jconrel.2003.10.012. View

10.

Rahman M, Ali A, Sjoholm E, Soindinsalo S, Wilen C, Bansal K . Significance of Polymers with "Allyl" Functionality in Biomedicine: An Emerging Class of Functional Polymers. Pharmaceutics. 2022; 14(4). PMC: 9025249. DOI: 10.3390/pharmaceutics14040798. View

11.

Wang H, Williams G, Wu J, Wu J, Niu S, Xie X . Pluronic F127-based micelles for tumor-targeted bufalin delivery. Int J Pharm. 2019; 559:289-298. DOI: 10.1016/j.ijpharm.2019.01.049. View

12.

Remko M, von der Lieth C . Theoretical study of gas-phase acidity, pKa, lipophilicity, and solubility of some biologically active sulfonamides. Bioorg Med Chem. 2004; 12(20):5395-403. DOI: 10.1016/j.bmc.2004.07.049. View

13.

Husseini G, Pitt W . Micelles and nanoparticles for ultrasonic drug and gene delivery. Adv Drug Deliv Rev. 2008; 60(10):1137-52. PMC: 2490710. DOI: 10.1016/j.addr.2008.03.008. View

14.

Teo J, Chin W, Ke X, Gao S, Liu S, Cheng W . pH and redox dual-responsive biodegradable polymeric micelles with high drug loading for effective anticancer drug delivery. Nanomedicine. 2016; 13(2):431-442. DOI: 10.1016/j.nano.2016.09.016. View

15.

Linn M, Collnot E, Djuric D, Hempel K, Fabian E, Kolter K . Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo. Eur J Pharm Sci. 2011; 45(3):336-43. DOI: 10.1016/j.ejps.2011.11.025. View

16.

Williams H, Trevaskis N, Charman S, Shanker R, Charman W, Pouton C . Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013; 65(1):315-499. DOI: 10.1124/pr.112.005660. View

17.

Granero G, Longhi M, Mora M, Junginger H, Midha K, Shah V . Biowaiver monographs for immediate release solid oral dosage forms: furosemide. J Pharm Sci. 2009; 99(6):2544-56. DOI: 10.1002/jps.22030. View

18.

Zhao L, Zhang W . Recent progress in drug delivery of pluronic P123: pharmaceutical perspectives. J Drug Target. 2017; 25(6):471-484. DOI: 10.1080/1061186X.2017.1289538. View

19.

Liu Z, Liu D, Wang L, Zhang J, Zhang N . Docetaxel-loaded pluronic p123 polymeric micelles: in vitro and in vivo evaluation. Int J Mol Sci. 2011; 12(3):1684-96. PMC: 3111627. DOI: 10.3390/ijms12031684. View

20.

Giacomelli C, Schmidt V, Borsali R . Specific interactions improve the loading capacity of block copolymer micelles in aqueous media. Langmuir. 2007; 23(13):6947-55. DOI: 10.1021/la700337s. View