A Recent Review of PLGA-PEG Hybrid Nanoparticles for Anticancer and Anti-Inflammatory Applications

Authors

  • Sina Matalqah Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
  • Zainab Lafi Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
  • Aya Y. Al-Kabariti Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan

DOI:

https://doi.org/10.35516/jjps.v18i1.2737

Keywords:

Nanotechnology, PLGA NP, Medical application, Cancer, Anti-inflammatory

Abstract

Numerous synthetic polymers have been investigated to be used in nanomedicine over the past few decades, particularly in drug delivery systems. Necessitating properties including non-toxic, biodegradable, and biocompatible. Among these, polylactic-co-glycolic acid (PLGA) which stands out due to its complete biodegradability and ability to self-assemble into nanometric micelles. However, their large diameter (150–200 nm), poor stability in aqueous media, and their removal from the bloodstream by the liver and spleen hindering the in vivo treatments. Polyethylene glycol (PEG) is the most widely used polymer in drug delivery systems, and the first PEGylated product has been on the market for over 20 years. PEG has a stealth behavior; therefore, it will not be recognized by the immune system. Further, PEG is hydrophilic polymer that could stabilize nanoparticles through steric rather than ionic effects. In this review article, the important of utilizing PLGA-PEG nanoparticles as polymeric drug carriers has been revised and the advantages of employing PLGA-PEG copolymer to form stable and well-defined, nanoparticles for drug delivery applications have been summarized. Moreover, the review aimed to shed light on the various methods employed in their preparation. Additionally, recent advancements in PLGA-PEG copolymer preparations for anti-cancer and anti-inflammatory therapies, are discussed in detail. The other applications of PGA-PEG have been extensively reviewed in other publications. Therefore, it was not addressed in this review.

References

Swami, A., et al. Nanoparticles for targeted and temporally controlled drug delivery. 2012: p. 9-29. DOI: https://doi.org/10.1007/978-1-4614-2305-8_2

Nsairat, H., et al. Development and validation of reversed-phase-HPLC method for simultaneous quantification of fulvestrant and disulfiram in liposomes. Bioanalysis, 2023; 15(23): p. 1393-1405. DOI: https://doi.org/10.4155/bio-2023-0137

Lafi, Z., N. Aboalhaija, and F. Afifi. Ethnopharmacological importance of local flora in the traditional medicine of Jordan: (A mini review). Jordan Journal of Pharmaceutical Sciences, 2022; 15(1): p. 132-144. DOI: https://doi.org/10.35516/jjps.v15i1.300

Wulff-Perez, M., et al. In vitro duodenal lipolysis of lipid-based drug delivery systems studied by HPLC–UV and HPLC–MS. International Journal of Pharmaceutics, 2014; 465(1-2): p. 396-404. DOI: https://doi.org/10.1016/j.ijpharm.2014.02.027

Saucier-Sawyer, J.K., et al. Systemic delivery of blood–brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue. 2015; 23(7-8): p. 736-749. DOI: https://doi.org/10.3109/1061186X.2015.1065833

Abd Ellah, N.H. and S.A.J.E.o.o.d.d. Abouelmagd. Surface functionalization of polymeric nanoparticles for tumor drug delivery: approaches and challenges. 2017; 14(2): p. 201-214. DOI: https://doi.org/10.1080/17425247.2016.1213238

Munef, A., Z. Lafi, and N. Shalan. Investigating anti-cancer activity of dual-loaded liposomes with thymoquinone and vitamin C. Therapeutic Delivery, 2024; 15(4): p. 267-278. DOI: https://doi.org/10.4155/tde-2023-0140

Zainab, L., T. Hiba, and A. Hanan. An updated assessment on anticancer activity of screened medicinal plants in Jordan: Mini review. Journal of Pharmacognosy and Phytochemistry, 2020; 9(5): p. 55-58. DOI: https://doi.org/10.22271/phyto.2020.v9.i5a.12423

George, A., P.A. Shah, and P.S.J.I.j.o.p. Shrivastav. Natural biodegradable polymers based nano-formulations for drug delivery: A review. 2019; 561: p. 244-264. DOI: https://doi.org/10.1016/j.ijpharm.2019.03.011

Mukherjee, C., et al. Recent Advances in Biodegradable Polymers–Properties, Applications and Future Prospects. 2023: p. 112068. DOI: https://doi.org/10.1016/j.eurpolymj.2023.112068

Alshaer, W., et al. Quality by design approach in liposomal formulations: Robust product development. Molecules, 2022; 28(1): p. 10. DOI: https://doi.org/10.3390/molecules28010010

Nsairat, H., et al. Impact of Nanotechnology on the Oral Delivery of Phyto-bioactive Compounds. Food Chemistry, 2023: p. 136438.

Patel, C.M., et al. Poly lactic glycolic acid (PLGA) as biodegradable polymer. 2010; 3(2): p. 353-360.

Makadia, H.K. and S.J.J.P. Siegel. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. 2011; 3(3): p. 1377-1397.

Lü, J.-M., et al. Current advances in research and clinical applications of PLGA-based nanotechnology. 2009; 9(4): p. 325-341. DOI: https://doi.org/10.1586/erm.09.15

Muthu, M.S., et al. PLGA nanoparticle formulations of risperidone: preparation and neuropharmacological evaluation. 2009; 5(3): p. 323-333. DOI: https://doi.org/10.1016/j.nano.2008.12.003

Knop, K., et al. Poly (ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. 2010; 49(36): p. 6288-6308. DOI: https://doi.org/10.1002/anie.200902672

Dingels, C. and H.J.H.M.S.Y.a.t.S.N.P.I. Frey. From Biocompatible to biodegradable: poly (ethylene glycol) s with predetermined breaking points. 2013: p. 167-190. DOI: https://doi.org/10.1007/12_2013_235

Cleveland, M.V., et al. New polyethylene glycol laxative for treatment of constipation in adults: a randomized, double-blind, placebo-controlled study. 2001; 94(5): p. 478-481. DOI: https://doi.org/10.1097/00007611-200194050-00006

Nsairat, H., et al. Impact of nanotechnology on the oral delivery of phyto-bioactive compounds. Food Chemistry, 2023; 424: p. 136438. DOI: https://doi.org/10.1016/j.foodchem.2023.136438

Alshaer, W., et al. Encapsulation of echinomycin in cyclodextrin inclusion complexes into liposomes: in vitro anti-proliferative and anti-invasive activity in glioblastoma. RSC Advances, 2019; 9(53): p. 30976-30988. DOI: https://doi.org/10.1039/C9RA05636J

Al Zubaidi Z.M., et al. Hyaluronic Acid–Coated Niosomes for Curcumin Targeted Delivery into Breast Cancer Cells. ChemistrySelect. 2024; 9(3):e202304649. DOI: https://doi.org/10.1002/slct.202304649

Sahu T., et al. Nanotechnology-Based Drug Delivery System: Current Strategies and Emerging Therapeutic Potential for Medical Science. 2021; 63:102487. DOI: https://doi.org/10.1016/j.jddst.2021.102487

Lafi Z., et al. Aptamer-Functionalized pH-Sensitive Liposomes for a Selective Delivery of Echinomycin into Cancer Cells. RSC Adv. 2021; 11(47):29164-29177. DOI: https://doi.org/10.1039/D1RA05138E

D’souza A.A., Shegokar R. Polyethylene Glycol (PEG): A Versatile Polymer for Pharmaceutical Applications. Eur. J. Pharm. Sci. 2016; 13(9):1257-1275. DOI: https://doi.org/10.1080/17425247.2016.1182485

Lafi Z., et al. Echinomycin: A Journey of Challenges. Jordan J. Pharm. Sci. 2023; 16(3). DOI: https://doi.org/10.35516/jjps.v16i3.918

Chen L., et al. Effects of Molecular Weight and Its Distribution of PEG Block on Micellization and Thermogellability of PLGA–PEG–PLGA Copolymer Aqueous Solutions. 2015; 48(11):3662-3671. DOI: https://doi.org/10.1021/acs.macromol.5b00168

Gref R., et al. Biodegradable Long-Circulating Polymeric Nanospheres. Science. 1994; 263(5153):1600-1603. DOI: https://doi.org/10.1126/science.8128245

Huh K.M., Cho Y.W., Park K.J.D.T. PLGA-PEG Block Copolymers for Drug Formulations. Drug Deliv. Technol. 2003; 3(5):42-44.

Cheng J., et al. Formulation of Functionalized PLGA-PEG Nanoparticles for In Vivo Targeted Drug Delivery. Biomaterials. 2007; 28(5):869-876.

Sánchez-López E., et al. Memantine Loaded PLGA PEGylated Nanoparticles for Alzheimer’s Disease: In Vitro and In Vivo Characterization. 2018; 16:1-16. DOI: https://doi.org/10.1186/s12951-018-0356-z

Hosseininasab S., et al. Retracted: Synthesis, Characterization, and In Vitro Studies of PLGA–PEG Nanoparticles for Oral Insulin Delivery. J. Control. Release. 2014; 84(3):307-315. DOI: https://doi.org/10.1111/cbdd.12318

Cheng J., et al. Formulation of Functionalized PLGA–PEG Nanoparticles for In Vivo Targeted Drug Delivery. Biomaterials. 2007; 28(5):869-876. DOI: https://doi.org/10.1016/j.biomaterials.2006.09.047

Khalil N.M., et al. Pharmacokinetics of Curcumin-Loaded PLGA and PLGA–PEG Blend Nanoparticles After Oral Administration in Rats. J. Pharm. Pharmacol. 2013; 101:353-360. DOI: https://doi.org/10.1016/j.colsurfb.2012.06.024

Andima M., et al. Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity. Nanomaterials. 2018; 10(4):232. DOI: https://doi.org/10.3390/pharmaceutics10040232

Beletsi A., Panagi Z., Avgoustakis K. Biodistribution Properties of Nanoparticles Based on Mixtures of PLGA with PLGA–PEG Diblock Copolymers. Int. J. Pharm. 2005; 298(1):233-241. DOI: https://doi.org/10.1016/j.ijpharm.2005.03.024

Afshari M., Derakhshandeh K., Hosseinzadeh L. Characterisation, Cytotoxicity, and Apoptosis Studies of Methotrexate-Loaded PLGA and PLGA-PEG Nanoparticles. J. Med. 2014; 31(3):239-245. DOI: https://doi.org/10.3109/02652048.2013.834991

Ali I., et al. Advances in Nanocarriers for Anticancer Drugs Delivery. 2016; 23(20):2159-2187. DOI: https://doi.org/10.2174/0929867323666160405111152

Rafiei P., Haddadi A.J. Docetaxel-Loaded PLGA and PLGA-PEG Nanoparticles for Intravenous Application: Pharmacokinetics and Biodistribution Profile. Int. J. Nanomedicine. 2017; p. 935-947.

Duceppe N., Tabrizian M.J. Advances in Using Chitosan-Based Nanoparticles for In Vitro and In Vivo Drug and Gene Delivery. Eur. J. Pharm. Sci. 2010; 7(10):1191-1207. DOI: https://doi.org/10.1517/17425247.2010.514604

Zhu G., Mallery S.R., Schwendeman S.P. Stabilization of Proteins Encapsulated in Injectable Poly (Lactide-Co-Glycolide). Nat. Biotechnol. 2000; 18(1):52-57. DOI: https://doi.org/10.1038/71916

Mallik A.K., et al. Poly (Lactic Acid)(PLA)-Based Nanosystems in Biomedical Applications. 2022; p. 63-89. DOI: https://doi.org/10.1002/9783527832095.ch20

Abudayah A.A.F. Implication of Nanotechnology for Pulmonary Delivery of Docetaxel. Jordan J. Pharm. Sci. 2023; 16(2):470-470. DOI: https://doi.org/10.35516/jjps.v16i2.1527

Rocha C.V., et al. PLGA-Based Composites for Various Biomedical Applications. Int. J. Mol. Sci. 2022; 23(4). DOI: https://doi.org/10.3390/ijms23042034

Al-Azzawi H., et al. Multifunctional Nanoparticles Recruiting Hyaluronic Acid Ligand and Polyplexes Containing Low Molecular Weight Protamine and ATP-Sensitive DNA Motif for Doxorubicin Delivery. J. Drug Deliv. Sci. Technol. 2022; 69:103169. DOI: https://doi.org/10.1016/j.jddst.2022.103169

Cao L.-B., Zeng S., Zhao W. Highly Stable PEGylated Poly (Lactic-Co-Glycolic Acid)(PLGA) Nanoparticles for the Effective Delivery of Docetaxel in Prostate Cancers. Nanoscale Res. Lett. 2016; 11(1):305. DOI: https://doi.org/10.1186/s11671-016-1509-3

Rafiei P., Haddadi A. Docetaxel-Loaded PLGA and PLGA-PEG Nanoparticles for Intravenous Application: Pharmacokinetics and Biodistribution Profile. Int. J. Nanomedicine. 2017; 12:935-947. DOI: https://doi.org/10.2147/IJN.S121881

Jin H., et al. EGFR-Targeting PLGA-PEG Nanoparticles as a Curcumin Delivery System for Breast Cancer Therapy. Nanoscale. 2017; 9(42):16365-16374. DOI: https://doi.org/10.1039/C7NR06898K

Gholizadeh S., et al. PLGA-PEG Nanoparticles for Targeted Delivery of the mTOR/PI3 Kinase Inhibitor Dactolisib to Inflamed Endothelium. Int. J. Pharm. 2018; 548(2):747-758. DOI: https://doi.org/10.1016/j.ijpharm.2017.10.032

Fathi Karkan S., Davaran S., Akbarzadeh A. Cisplatin-Loaded Superparamagnetic Nanoparticles Modified with PCL-PEG Copolymers as a Treatment of A549 Lung Cancer Cells. Nanomedicine Res. J. 2019; 4(4):209-219.

Wani S.U.D., et al. A Review on Nanoparticles Categorization, Characterization, and Applications in Drug Delivery Systems. Vibrational Spectroscopy. 2022; 121:103407. DOI: https://doi.org/10.1016/j.vibspec.2022.103407

Amirsaadat S., et al. Metformin and Silibinin Co-Loaded PLGA-PEG Nanoparticles for Effective Combination Therapy Against Human Breast Cancer Cells. J. Drug Deliv. Sci. Technol. 2021; 61:102107.

Fahmy S.A., et al. PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum Harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities. Pharmaceutics. 2022; 14(1):142. DOI: https://doi.org/10.3390/pharmaceutics14010142

Minh N.H., et al. Stability of Soluble Honokiol Loaded PLGA-PEG Nanoparticles Under Normal and Accelerated-Aging Conditions. Adv. Nat. Sci. Nanoscience Nanotechnol. 2023; 14(3):035004. DOI: https://doi.org/10.1088/2043-6262/ace3b9

Watcharadulyarat N., et al. PEG-PLGA Nanoparticles for Encapsulating Ciprofloxacin. Sci. Rep. 2023; 13(1):266. DOI: https://doi.org/10.1038/s41598-023-27500-y

Ramôa A.M., et al. Antimicrobial Peptide-Grafted PLGA-PEG Nanoparticles to Fight Bacterial Wound Infections. Biomater. Sci. 2023; 11(2):499-508. DOI: https://doi.org/10.1039/D2BM01127A

Jafari-Gharabaghlou D., et al. Potentiation of Folate-Functionalized PLGA-PEG Nanoparticles Loaded with Metformin for the Treatment of Breast Cancer: Possible Clinical Application. 2023; 50(4):3023-3033. DOI: https://doi.org/10.1007/s11033-022-08171-w

Amirsaadat S., et al. Metformin and Silibinin Co-Loaded PLGA-PEG Nanoparticles for Effective Combination Therapy Against Human Breast Cancer Cells. 2021; 61:102107. DOI: https://doi.org/10.1016/j.jddst.2020.102107

Khaledi S., et al. Preparation and Characterization of PLGA-PEG-PLGA Polymeric Nanoparticles for Co-Delivery of 5-Fluorouracil and Chrysin. 2020; 31(9):1107-1126. DOI: https://doi.org/10.1080/09205063.2020.1743946

Dhar S., et al. Targeted Delivery of Cisplatin to Prostate Cancer Cells by Aptamer Functionalized Pt (IV) Prodrug-PLGA-PEG Nanoparticles. 2008; 105(45):17356-17361. DOI: https://doi.org/10.1073/pnas.0809154105

Farokhzad O.C., et al. Targeted Nanoparticle-Aptamer Bioconjugates for Cancer Chemotherapy In Vivo. 2006; 103(16):6315-6320. DOI: https://doi.org/10.1073/pnas.0601755103

Fekri Aval S., et al. Gene Silencing Effect of SiRNA-Magnetic Modified with Biodegradable Copolymer Nanoparticles on hTERT Gene Expression in Lung Cancer Cell Line. Artif Cells Nanomed Biotechnol. 2016; 44(1):188-193. DOI: https://doi.org/10.3109/21691401.2014.934456

Vij N. Synthesis and Evaluation of Airway-Targeted PLGA-PEG Nanoparticles for Drug Delivery in Obstructive Lung Diseases. In: Nanoparticles in Biology and Medicine: Methods and Protocols. Springer, 2020; 147-154.

Vij N., et al. Neutrophil Targeted Nano-Drug Delivery System for Chronic Obstructive Lung Diseases. 2016; 12(8):2415-2427. DOI: https://doi.org/10.1016/j.nano.2016.06.008

Galindo-Camacho R.M., et al. Cell Penetrating Peptides-Functionalized Licochalcone-A-Loaded PLGA Nanoparticles for Ocular Inflammatory Diseases: Evaluation of In Vitro Anti-Proliferative Effects, Stabilization by Freeze-Drying and Characterization of an In-Situ Forming Gel. Int. J. Pharm. 2023; 639:122982. DOI: https://doi.org/10.1016/j.ijpharm.2023.122982

Palacio J., et al. Preparation and Evaluation of PLGA-PEG/Gusperimus Nanoparticles as a Controlled Delivery Anti-Inflammatory Drug. 2022; 77:103889.

Li Z., et al. Prevention of Oxidized Low-Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound. 2017; 18(4):815. DOI: https://doi.org/10.3390/ijms18040815

Mohan L.J., et al. Optimising PLGA-PEG Nanoparticle Size and Distribution for Enhanced Drug Targeting to the Inflamed Intestinal Barrier. Pharmaceutics. 2020; 12(11). DOI: https://doi.org/10.3390/pharmaceutics12111114

Ismail J., et al. PEG-Lipid-PLGA Hybrid Particles for Targeted Delivery of Anti-Inflammatory Drugs. Pharmaceutics. 2024; 16(2). DOI: https://doi.org/10.3390/pharmaceutics16020187

Palacio J., et al. Preparation and Evaluation of PLGA-PEG/Gusperimus Nanoparticles as a Controlled Delivery Anti-Inflammatory Drug. J. Drug Deliv. Sci. Technol. 2022; 77:103889. DOI: https://doi.org/10.1016/j.jddst.2022.103889

Vij N. Synthesis and Evaluation of Airway-Targeted PLGA-PEG Nanoparticles for Drug Delivery in Obstructive Lung Diseases. Methods Mol Biol. 2020; 2118:147-154. DOI: https://doi.org/10.1007/978-1-0716-0319-2_11

Galindo R., et al. Development of Peptide Targeted PLGA-PEGylated Nanoparticles Loading Licochalcone-A for Ocular Inflammation. Pharmaceutics. 2022; 14(2):285. DOI: https://doi.org/10.3390/pharmaceutics14020285

Wang J., et al. Prophylactic and Therapeutic Potential of Magnolol-Loaded PLGA-PEG Nanoparticles in a Chronic Murine Model of Allergic Asthma. Front. Bioeng. Biotechnol. 2023; 11:1182080. DOI: https://doi.org/10.3389/fbioe.2023.1182080

Peng K.T., et al. Treatment of Osteomyelitis with Teicoplanin-Encapsulated Biodegradable Thermosensitive Hydrogel Nanoparticles. Biomaterials. 2010; 31(19):5227-5236. DOI: https://doi.org/10.1016/j.biomaterials.2010.03.027

Cao H., et al. Effects of rAmb a 1-Loaded PLGA-PEG Nanoparticles in a Murine Model of Allergic Conjunctivitis. Molecules. 2022; 27(3). DOI: https://doi.org/10.3390/molecules27030598

Dave V., et al. PEG-PLGA-Hybrid Nanoparticles Loaded with Etoricoxib-Phospholipid Complex for Effective Treatment of Inflammation in Rat Model. J. Microencapsulation. 2019; 36(3):236-249. DOI: https://doi.org/10.1080/02652048.2019.1617362

Danhier F., et al. PLGA-Based Nanoparticles: An Overview of Biomedical Applications. J. Control. Release. 2012; 161(2):505-522. DOI: https://doi.org/10.1016/j.jconrel.2012.01.043

Makadia H.K., Siegel S.J. Poly Lactic-Co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers. 2011; 3(3):1377-1397. DOI: https://doi.org/10.3390/polym3031377

Ishida T., Kiwada H. Accelerated Blood Clearance (ABC) Phenomenon Upon Repeated Injection of PEGylated Liposomes. Int. J. Pharm. 2008; 354(1-2):56-62. DOI: https://doi.org/10.1016/j.ijpharm.2007.11.005

Brigger I., Dubernet C., Couvreur P. Nanoparticles in Cancer Therapy and Diagnosis. Adv. Drug Deliv. Rev. 2012; 64:24-36. DOI: https://doi.org/10.1016/j.addr.2012.09.006

Downloads

Published

2025-03-25

How to Cite

Matalqah, S., Lafi, Z., & Al-Kabariti, A. Y. (2025). A Recent Review of PLGA-PEG Hybrid Nanoparticles for Anticancer and Anti-Inflammatory Applications. Jordan Journal of Pharmaceutical Sciences, 18(1), 180–195. https://doi.org/10.35516/jjps.v18i1.2737

Issue

Section

Articles