PEGylated Ethyl Cellulose Micelles As a Nanocarrier for Drug Delivery

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Apr 28

PMID 35479870

Authors

Amarnath Singam

Naresh Killi

Pratikshkumar R Patel

Rathna V N Gundloori

Affiliations

Soon will be listed here.

Abstract

Natural polymers provide a better alternative to synthetic polymers in the domain of drug delivery systems (DDSs) because of their renewability, biocompatibility, and low immunogenicity; therefore, they are being studied for the development of bulk/nanoformulations. Likewise, current methods for engineering natural polymers into micelles are in their infancy, and in-depth studies are required using natural polymers as controlled DDSs. Accordingly, in our present study, a new micellar DDS was synthesized using ethyl cellulose (EC) grafted with polyethylene glycol (PEG); it was characterized, its properties, cell toxicity, and hemocompatibility were evaluated, and its drug release kinetics were demonstrated using doxorubicin (DOX) as a model drug. Briefly, EC was grafted with PEG to form the amphiphilic copolymers EC-PEG1 and EC-PEG2 with varying PEG concentrations, and nano-micelles were prepared with and without the drug (DOX) a dialysis method; the critical micelle concentrations (CMCs) were recorded to be 0.03 mg mL and 0.00193 mg mL for EC-PEG1 and EC-PEG2, respectively. The physicochemical properties of the respective nano-micelles were evaluated various characterization techniques. The morphologies of the nano-micelles were analyzed transmission electron microscopy (TEM), and the average size of the nano-micelles was recorded to be ∼80 nm. , drug release studies were done for 48 h, where 100% DOX release was recorded at pH 5.5 and 52% DOX release was recorded at pH 7.4 from the micelles. In addition, cytotoxicity studies suggested that DOX-loaded micelles were potent in killing MDA-MB-231 and MCF-7 cancer cells, and the blank micelles were non-toxic toward cancerous and normal cells. A cellular uptake study fluorescence microscopy indicated the internalization of DOX-loaded micelles by cancer cells, delivering the DOX into the cellular compartments. Based on these studies, we concluded that the developed material should be studied further studies to understand its potential as a controlled DDS to treat cancer.

Citing Articles

Development and Characterization of Biocompatible Cellulose-Tetraphenylethylene Hydrazone Self-Assembling Nanomicelles with Acidity-Triggered Release of Doxorubicin for Cancer Therapy.

Rupel K, Fanfoni L, Dus J, Tommasini M, Porrelli D, Medagli B Curr Issues Mol Biol. 2024; 46(12):14244-14258.

PMID: 39727981 PMC: 11674980. DOI: 10.3390/cimb46120853.

Critical Review of Food Colloidal Delivery System for Bioactive Compounds: Physical Characterization and Application.

Wang B, LvYe J, Yang S, Shi Y, Chen Q Foods. 2024; 13(16).

PMID: 39200523 PMC: 11353541. DOI: 10.3390/foods13162596.

Breaking barriers: The potential of nanosystems in antituberculosis therapy.

Carnero Canales C, Marquez Cazorla J, Marquez Cazorla R, Roque-Borda C, Polinario G, Figueroa Banda R Bioact Mater. 2024; 39:106-134.

PMID: 38783925 PMC: 11112550. DOI: 10.1016/j.bioactmat.2024.05.013.

Sponges from Plasma Treated Cellulose Nanofibers Grafted with Poly(ethylene glycol)methyl Ether Methacrylate.

Chiulan I, Panaitescu D, Serafim A, Radu E, Ionita G, Raditoiu V Polymers (Basel). 2022; 14(21).

PMID: 36365713 PMC: 9656828. DOI: 10.3390/polym14214720.

References

Biswas S, Kumari P, Lakhani P, Ghosh B . Recent advances in polymeric micelles for anti-cancer drug delivery. Eur J Pharm Sci. 2016; 83:184-202. DOI: 10.1016/j.ejps.2015.12.031. View

Chen J, Qiu X, Ouyang J, Kong J, Zhong W, Xing M . pH and reduction dual-sensitive copolymeric micelles for intracellular doxorubicin delivery. Biomacromolecules. 2011; 12(10):3601-11. DOI: 10.1021/bm200804j. View

Arora H, Jensen M, Yuan Y, Wu A, Vogt S, Paunesku T . Nanocarriers enhance Doxorubicin uptake in drug-resistant ovarian cancer cells. Cancer Res. 2011; 72(3):769-78. PMC: 3657469. DOI: 10.1158/0008-5472.CAN-11-2890. View

Yuan W, Yuan J, Zhang F, Xie X . Syntheses, characterization, and in vitro degradation of ethyl cellulose-graft-poly(epsilon-caprolactone)-block-poly(L-lactide) copolymers by sequential ring-opening polymerization. Biomacromolecules. 2007; 8(4):1101-8. DOI: 10.1021/bm0610018. View

Balzus B, Colombo M, Sahle F, Zoubari G, Staufenbiel S, Bodmeier R . Comparison of different in vitro release methods used to investigate nanocarriers intended for dermal application. Int J Pharm. 2016; 513(1-2):247-254. DOI: 10.1016/j.ijpharm.2016.09.033. View

Gong J, Chen M, Zheng Y, Wang S, Wang Y . Polymeric micelles drug delivery system in oncology. J Control Release. 2012; 159(3):312-23. DOI: 10.1016/j.jconrel.2011.12.012. View

Hwang D, Ramsey J, Kabanov A . Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. Adv Drug Deliv Rev. 2020; 156:80-118. PMC: 8173698. DOI: 10.1016/j.addr.2020.09.009. View

Gref R, Domb A, Quellec P, Blunk T, Muller R, Verbavatz J . The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev. 2014; 16(2-3):215-233. PMC: 4144462. DOI: 10.1016/0169-409X(95)00026-4. View

Cabral H, Kataoka K . Progress of drug-loaded polymeric micelles into clinical studies. J Control Release. 2014; 190:465-76. DOI: 10.1016/j.jconrel.2014.06.042. View

10.

Su X, Yang Z, Tan K, Chen J, Huang J, Li Q . Preparation and characterization of ethyl cellulose film modified with capsaicin. Carbohydr Polym. 2020; 241:116259. DOI: 10.1016/j.carbpol.2020.116259. View

11.

Lv S, Li M, Tang Z, Song W, Sun H, Liu H . Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy. Acta Biomater. 2013; 9(12):9330-42. DOI: 10.1016/j.actbio.2013.08.015. View

12.

Asadi H, Rostamizadeh K, Salari D, Hamidi M . Preparation of biodegradable nanoparticles of tri-block PLA-PEG-PLA copolymer and determination of factors controlling the particle size using artificial neural network. J Microencapsul. 2011; 28(5):406-16. DOI: 10.3109/02652048.2011.576784. View

13.

Justus C, Dong L, Yang L . Acidic tumor microenvironment and pH-sensing G protein-coupled receptors. Front Physiol. 2013; 4:354. PMC: 3851830. DOI: 10.3389/fphys.2013.00354. View

14.

Fang J, Nakamura H, Maeda H . The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev. 2010; 63(3):136-51. DOI: 10.1016/j.addr.2010.04.009. View

15.

Ding B, Ye Y, Cheng J, Wang K, Luo J, Jiang B . TEMPO-mediated selective oxidation of substituted polysaccharides--an efficient approach for the determination of the degree of substitution at C-6. Carbohydr Res. 2008; 343(18):3112-6. DOI: 10.1016/j.carres.2008.09.005. View

16.

Lv S, Tang Z, Li M, Lin J, Song W, Liu H . Co-delivery of doxorubicin and paclitaxel by PEG-polypeptide nanovehicle for the treatment of non-small cell lung cancer. Biomaterials. 2014; 35(23):6118-29. DOI: 10.1016/j.biomaterials.2014.04.034. View

17.

Kaldeus T, Nordenstrom M, Carlmark A, Wagberg L, Malmstrom E . Insights into the EDC-mediated PEGylation of cellulose nanofibrils and their colloidal stability. Carbohydr Polym. 2017; 181:871-878. DOI: 10.1016/j.carbpol.2017.11.065. View

18.

Wasilewska K, Winnicka K . Ethylcellulose-A Pharmaceutical Excipient with Multidirectional Application in Drug Dosage Forms Development. Materials (Basel). 2019; 12(20). PMC: 6829386. DOI: 10.3390/ma12203386. View

19.

Wang H, Zhao Y, Wu Y, Hu Y, Nan K, Nie G . Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials. 2011; 32(32):8281-90. DOI: 10.1016/j.biomaterials.2011.07.032. View

20.

Zhao Q, Han B, Wang Z, Gao C, Peng C, Shen J . Hollow chitosan-alginate multilayer microcapsules as drug delivery vehicle: doxorubicin loading and in vitro and in vivo studies. Nanomedicine. 2007; 3(1):63-74. DOI: 10.1016/j.nano.2006.11.007. View