Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system
Source abstract
Abstract
During the past decades many synthetic polymers have been studied for nanomedicine applications and in particular as drug delivery systems. For this purpose, polymers must be non-toxic, biodegradable, and biocompatible. Polylactic-co-glycolic acid (PLGA) is one of the most studied polymers due to its complete biodegradability and ability to self-assemble into nanometric micelles that are able to entrap small molecules like drugs and to release them into body in a time-dependent manner. Despite fine qualities, using PLGA polymeric nanoparticles for in vivo applications still remains an open challenge due to many factors such as poor stability in water, big diameter (150–200 nm), and the removal of these nanocarriers from the blood stream by the liver and spleen thus reducing the concentration of drugs drastically in tumor tissue. Polyethylene glycol (PEG) is the most used polymers for drug delivery applications and the first PEGylated product is already on the market for over 20 years. This is due to its stealth behavior that inhibits the fast recognition by the immune system (opsonization) and generally leads to a reduced blood clearance of nanocarriers increasing blood circulation time. Furthermore, PEG is hydrophilic and able to stabilize nanoparticles by steric and not ionic effects especially in water. PLGA–PEG block copolymer is an emergent system because it can be easily synthesized and it possesses all good qualities of PLGA and also PEG capability so in the last decade it arose as one of the most promising systems for nanoparticles formation, drug loading, and in vivo drug delivery applications. This review will discuss briefly on PLGA-b-PEG synthesis and physicochemical properties, together with its improved qualities with respect to the single PLGA and PEG polymers. Moreover, we will focus on but in particular will treat nanoparticles formation and uses as new drug delivery system for nanomedical applications.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Advanced Drug Delivery Systems · Graphene and Nanomaterials Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (82)
Show source-provided references
1. Abuchowski A, Van Es T, Palczuk NC, Davis FF (1977) Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J Biol Chem 252:3582–358610.1016/S0021-9258(17)40292-4 ↗
2. Alex R, Bodmeier R (1989) Encapsulation of water-soluble drugs by a modified solvent evaporation method: effect of process and formulation variables on drug entrapment. J Microencapsul 7:347–35510.3109/02652049009021845 ↗
3. Ashjari M, Khoee S, Mahdavian AR, Rahmatolahzadeh R (2012) Self-assembled nanomicelles using PLGA–PEG amphiphilic block copolymer for insulin delivery: a physicochemical investigation and determination of CMC values. J Mater Sci: Mater Med 23:943–95310.1007/s10856-012-4562-1 ↗
4. Astete CE, Sabliov CM (2006) Synthesis and characterization of PLGA nanoparticles. J Biomater Sci Polym Ed 17:247–28910.1163/156856206775997322 ↗
5. Avgoustakis K, Beletsi A, Panagi Z, Karydas AG, Klepetsanis P, Ithakissios DS (2002) PLGA–mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties. J Control Release 79:123–13510.1016/S0168-3659(01)00530-2 ↗
6. Avgoustakis K, Beletsi A, Panagi Z, Klepetsanis P, Livaniou E, Evangelatos G, Ithakissios DS (2003) Effect of copolymer composition on physicochemical characteristics, in vitro stability, and biodistribution of PLGA–mPEG nanoparticles. Int J Pharm 259:115–12710.1016/S0378-5173(03)00224-2 ↗
7. Bazile D, Prud’Homme C, Bassoulet MT, Marlard M, Spenlehauer G, Veillard M (1995) Stealth Me.PEG–PLA nanoparticles avoid uptake by mononuclear phagocytes system. J Pharm Sci 84:493–49810.1002/jps.2600840420 ↗
8. Beletsi A, Leontiadis L, Klepetsanis P, Ithakissios DS, Avgoustakis K (1999) Effect of preparative variables on the properties of poly(dl-lactide-co-glycolide)–methoxypoly(ethyleneglycol) copolymers related to their application in controlled drug delivery. Int J Pharm 182:187–19710.1016/S0378-5173(99)00058-7 ↗
9. Beletsi A, Panagi Z, Avgoustakis K (2005) Biodistribution properties of nanoparticles based on mixtures of PLGA with PLGA–PEG diblock copolymers. Int J Pharm 298:233–24110.1016/j.ijpharm.2005.03.024 ↗
10. Benoit JP, Marchais H, Rolland H, Velde VV (1996) Biodegradable microspheres. In: Benita S (ed) Advances in production technology microencapsulation. Methods and industrial applications. Marcel Dekker, New York, pp 36–72
11. Bouclier C, Moine L, Hillaireau H, Marsaud V, Oplon P, Connault E, Ccouvreur P, Fattal E, Renoir JM (2008) Physicochemical characteristics and preliminary in vivo evaluation of nanocapsules loaded with siRNA targeting estrogen receptor alpha. Biomacromolecules 9:2881–289010.1021/bm800664c ↗
12. Chen J, Li S, Shen Q, He H, Zhang Y (2011) Enhanced cellular uptake of folic acid-conjugated PLGA–PEG nanoparticles loaded with vincristine sulfate in human breast cancer. Drug Dev Ind Pharm 37:1339–134610.3109/03639045.2011.575162 ↗
13. Chen J, Li S, Shen Q (2012) Folic acid and cell-penetrating peptide conjugated PLGA–PEG bifunctional nanoparticles for vincristine sulfate delivery. Eur J Pharm Sci 47:430–44310.1016/j.ejps.2012.07.002 ↗
14. Cheng J, Teply BA, Sherifi I, Sung J, Luther G, Gu FX, Levy-Nissenbaum E, Radovic-Moreno AF, Langer R, Farokhzad OC (2007) Formulation of functionalized PLGA–PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 28:869–87610.1016/j.biomaterials.2006.09.047 ↗
15. Cleveland MV, Flavin DP, Ruben RA, Epstein RM, Clark GE (2001) New polyethylene glycol laxative for treatment of constipation in adults: a randomized, double-blind, placebo-controlled study. South Med J 94:478–48110.1097/00007611-200105000-00006 ↗
16. Comes Franchini M, Bonini BF, Camaggi CM, Gentili D, Pession A, Rani M, Strocchi E (2010a) Design and synthesis of novel pyrazoles for nanomedicine applications against malignant gliomas. Eur J Med Chem 45:2024–203310.1016/j.ejmech.2010.01.014 ↗
17. Comes Franchini M, Ponti J, Lemor R, Fournelle M, Broggi F, Locatelli E (2010b) Polymeric entrapped thiol-coated gold nanorods: cytotoxicity and suitability as molecular optoacoustic contrast agent. J Mater Chem 20:10908–1091410.1039/c0jm02209h ↗
18. Danhier F, Lecouturier N, Vroman B, Jérôme C, Marchand-Brynaert J, Feron O, Préat V (2009) Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J Control Release 133:11–1710.1016/j.jconrel.2008.09.086 ↗
19. Dhar S, Gu FX, Langer R, Farokhzad OC, Lippard SJ (2008) Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA–PEG nanoparticles. Proc Natl Acad Sci USA 105:17356–1736110.1073/pnas.0809154105 ↗
20. Dong Y, Feng S–S (2004) Methoxy poly(ethylene glycol)-poly(lactide) (MPEG–PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials 25:2843–284910.1016/j.biomaterials.2003.09.055 ↗
21. Duceppe N, Tabrizian M (2010) Advances in using chitosan-based nanoparticles for in vitro and in vivo drug and gene delivery. Expert Opin Drug Deliv 7:1191–120710.1517/17425247.2010.514604 ↗
22. Duncan R, Ringsdorf H, Satchi-Fainaro R (2006) Polymer therapeutics—polymers as drugs, drug and protein conjugates and gene delivery systems: past, present and future opportunities. Adv Polym Sci 192:1–810.1007/12_037 ↗
23. Dunn SE, Coombes AGA, Garnett MC, Davis SS, Davies MC, Illum L (1997) In vitro cell interaction and in vivo biodistribution of poly(lactide-co-glycolide) nanospheres surface modified by poloxamer and poloxamine copolymers. J Control Release 44:65–7610.1016/S0168-3659(96)01504-0 ↗
24. Esmaeili F, Ghahremani MH, Ostad SN, Atyabi F, Seydabadi M, Malekshani MR, Amini M, Dinarvand R (2008) Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA–PEG-folate conjugate. J Drug Target 16:415–42310.1080/10611860802088630 ↗
25. Farokhzad OC, Cheng J, Teply BA, Sherifi I, Jon S, Kantoff PW, Richie JP, Langer R (2006) Targeted nanoparticle–aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci USA 103:6315–632010.1073/pnas.0601755103 ↗
26. Feczkò T, Toth J, Gyenis J (2008) Comparison of the preparation of PLGA–BSA nano- and microparticles by PVA, polaxamer and PVP. Colloid Surf A 319:188–19510.1016/j.colsurfa.2007.07.011 ↗
27. Feczkò T, Toth J, Dosa G, Gyenis J (2011) Optimization of protein encapsulation in PLGA nanoparticles. Chem Eng Process 50:757–76510.1016/j.cep.2011.06.008 ↗
28. Gentili D, Ori G, Comes Franchini M (2009) Double phase transfer of gold nanorods for surface functionalization and entrapment into PEG-based nanocarriers. Chem Comm 39:5874–587610.1039/b911582j ↗
29. Ginlding DK, Reed AM (1979) Biodegradable polymers for use in surgery. Polyglycolic/poy(lactic acid) homo- and copolymers. Polymer 20:1459–146410.1016/0032-3861(79)90009-0 ↗
30. Graf N, Bielenberg DR, Kolishetti N, Muus C, Banyard J, Farokhzad OC, Lippard SJ (2012) ανβ3 Integrin-Targeted PLGA–PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug. ACS Nano 6:4530–453910.1021/nn301148e ↗
31. Greenwald RB, Choe YH, McGuire J, Conover CD (2003) Effective drug delivery by PEGylated drug conjugates. Adv Drug Deliv Rev 55:217–25010.1016/S0169-409X(02)00180-1 ↗
32. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R (1994) Biodegradable long-circulating polymeric nanospheres. Science 263:1600–160310.1126/science.8128245 ↗
33. Gref R, Domb A, Quellec P, Blunk T, Muller RH, Verbavatz JM, Langer R (1995) The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev 16:215–23310.1016/0169-409X(95)00026-4 ↗
34. Grobmyer SR, Moudgil BM (2010) Cancer nanotechnology: methods and protocols. Method Mol Biol 624:1–39610.1007/978-1-60761-609-2_1 ↗
35. Guo J, Gao X, Su L, Xia H, Gu G, Pang Z, Jiang X, Yao L, Chen J, Chen H (2011) Aptamer-functionalized PEG–PLG Ananoparticles for enhanced anti-glioma drug delivery. Biomaterials 32:8010–802010.1016/j.biomaterials.2011.07.004 ↗
36. Hans ML, Lowman AM (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–32710.1016/S1359-0286(02)00117-1 ↗
37. Huh KM, Cho YW, Park K (2003) PLGA–PEG block copolymers for drug formulations. Drug Dev Deliv 3:5
38. Iwata M, McGinity JW (1992) Preparation of multi-phase microspheres of poly(lactic acid) and poly(lactic-co-glycolic acid) containing a W:O emulsion by a multiple solvent evaporation technique. J Microencapsul 7:201–214
39. Joralemon MJ, McRae S, Emrick T (2010) PEGylated polymers for medicine: from conjugation to self-assembled systems. Chem Comm 46:1377–139310.1039/b920570p ↗
40. Khalil NM, Frabel do Nascimento TC, Casa DM, Dalmolin LF, de Mattos AC, Hoss I, Romano MA, Mainardes RM (2013) Pharmacokinetics of curcumin-loaded PLGA and PLGA–PEG blend nanoparticles after oral administration in rats. Coll Surf B: Biointerfaces 101:353–36010.1016/j.colsurfb.2012.06.024 ↗
41. Knop K, Hoogenboom R, Fischer D, Schubert US (2010) Poly(ethylene glycol) in drug delivery: pros and cons as Wellas potential alternatives. Angew Chem Int Ed 49:6288–630810.1002/anie.200902672 ↗
42. Kreuter J (1994) Colloidal drug delivery systems. Dekker, New York
43. Kreuter J (2004) Nanoparticles as drug delivery systems. Encycl Nanosci Nanotechnol 7:161–180
44. Kumar N, Ravikumarb MVN, Domb AJ (2001) Biodegradable block copolymers. Adv Drug Deliv Rev 53:23–4410.1016/S0169-409X(01)00219-8 ↗
45. Lewis DH (1990) Controlled release of bioactive agents from lactide/glycolide polymers. In: Chasin M, Langer R (eds) Biodegradable polymers as drug delivery systems, drugs and the pharmaceutical sciences. Marcel Dekker, New York, pp 1–41
46. Li S, McCarthy SP (1999) Influence of crystallinity and stereochemistry on the enzymatic degradation of poly(lactide)s. Macromolecules 32:4454–445610.1021/ma990117b ↗
47. Li YP, Pei YY, Zhang XY, Gu ZH, Zhou ZH, Yuan WF, Zhou JJ, Zhu JH, Gao XJ (2001) PEGylated PLGA nanoparticles as protein carriers: synthesis preparation and biodistribution in rats. J Control Release 71:203–21110.1016/S0168-3659(01)00218-8 ↗
48. Liang C, Yang Y, Ling Y, Huang Y, Li T, Li X (2011) Improved therapeutic effect of folate-decorated PLGA–PEG nanoparticles for endometrial carcinoma. Bioorganic Med Chem 19:4057–406610.1016/j.bmc.2011.05.016 ↗
49. Liu Y, Miyoshi H, Nakamura M (2007) Nanomedicine for drug delivery and imaging: a promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. Int J Cancer 120:2527–253710.1002/ijc.22709 ↗
50. Locatelli E, Ori G, Fournelle M, Lemor R, Montorsi M, Comes Franchini M (2011) Click chemistry for the assembly of gold nanorods and silver nanoparticles. Chem Eur J 17:9052–905610.1002/chem.201101027 ↗
51. Locatelli E, Broggi F, Ponti J, Marmorato P, Franchini F, Lena S, Comes Franchini M (2012) Lipophilic silver nanoparticles and their polymeric entrapment into targeted-PEG-based micelles for the treatment of glioblastoma. Adv Healthcare Mater 1:342–34710.1002/adhm.201100047 ↗
52. Lu JM, Wang X, Marin-Muller C, Wang H, Lin PH, Yao Q, Chen C (2009) Current advances in research and clinical applications of PLGA-based nanotechnology. Expert Rev Mol Diagn 9:325–34110.1586/erm.09.15 ↗
53. Luo G, Yu X, Jin C, Yang F, Fu D, Long J, Xu J, Zhan C, Lu W (2010) LyP-1-conjugated nanoparticles for targeting drug delivery to lymphatic metastatic tumors. Int J Pharm 385:150–15610.1016/j.ijpharm.2009.10.014 ↗
54. Magenheim B, Benita S (1991) Nanoparticle characterization : a comprehensive physicochemical approach. S.T.P. Pharma Sci 1:221–241
55. Magenheim B, Levy MY, Benita S (1993) A new in vitro technique for the evaluation of drug release profiles from colloidal carriers-ultrafiltration technique at low pressure. Int J Pharm 94:115–12310.1016/0378-5173(93)90015-8 ↗
56. McCarron PA, Hall M (2004) Pharmaceutical nanotechnology. Encycl Nanosci Nanotechnol 8:469–487
57. Mehnert W, Mäder K (2012) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. doi: 10.1016/j.addr.2012.09.021
58. Moghimi SM, Porter CJH, Muir IS, Illum L, Davis SS (1991) Non phagocytic uptake of intravenously injected microspheres in rat spleen-influence of particles-size and hydrophilic coating. Biochem Biophys Res Commun 177:861–86610.1016/0006-291X(91)91869-E ↗
59. Mosqueira VCF, Lengrand P, Morgat JL, Vert M, Mysiakine E, Gref R, Devissaguet JL, Barratt G (2001) Biodistribution of long-circulating PEG-grafted nanocapsules in mice: effects of PEG chain length and density. Pharm Res 18:1411–141910.1023/A:1012248721523 ↗
60. Muller RH (1991) Colloidal carriers for controlled drug delivery and targeting: modification, characterisation and in vivo distribution. CRC Press, Stuttgart
61. Muthu MS (2009) Nanoparticles based on PLGA and its co-polymer: an overview. Asian J Pharm 3:266–27710.4103/0973-8398.59948 ↗
62. Oh JK (2011) Polylactide (PLA)-based amphiphilic block copolymers: synthesis, self-assembly, and biomedical applications. Soft Matter 7:5096–510810.1039/c0sm01539c ↗
63. Oupicky D, Ogris M, Howard KA, Dash PR, Ulbrich K, Seymour LW (2002) Importance of lateral and steric stabilization of polyelectrolyte gene delivery vectors for extended systemic circulation. Mol Ther 5:463–47210.1006/mthe.2002.0568 ↗
64. Owens DE III, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–10210.1016/j.ijpharm.2005.10.010 ↗
65. Park TG (1994) Degradation of poly(d, l-lactic acid) microspheres: effect of molecular weight. J Control Release 30:538–546
66. Park JH, Lee S, Kim JH, Park K, Kim K, Kwon IC (2008) Polymeric nanomedicine for cancer therapy. Prog Polym Sci 33:113–13710.1016/j.progpolymsci.2007.09.003 ↗
67. Peracchia MT, Gref R, Minamitake Y, Domb A, Lotan N, Langer R (1997) PEG-coated nanospheres from amphiphilic diblock and multiblock copolymers: investigation of their drug encapsulation and release characteristics. J Control Release 46:23–22310.1016/S0168-3659(96)01597-0 ↗
68. Redhead HM, Davis SS, Illum L (2001) Drug delivery in poly(lactide-co-glycolide) nanoparticles surface modified with poloxamer 407 and poloxamine 908: in vitro characterisation and in vivo evaluation. J Control Release 70:353–36310.1016/S0168-3659(00)00367-9 ↗
69. Schmaljohann D (2006) Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 58:1655–167010.1016/j.addr.2006.09.020 ↗
70. Schubert S, Delaney JT, Schubert US (2011) Nanoprecipitation and nanoformulation of polymers: from history to powerful possibilities beyond poly(lactic acid). Soft Matter 7:1581–158810.1039/C0SM00862A ↗
71. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–2010.1016/S0168-3659(00)00339-4 ↗
72. Vinagradov SV, Bronich TK, Kabanov AV (2002) Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells. Adv Drug Deliv Rev 54:223–23310.1016/S0169-409X(02)00018-2 ↗
73. Vinod Prabhu, Siddik Uzzaman, Berlin Grace VM, Guruvayoorappan C (2011) Nanoparticles in drug delivery and cancer therapy: the giant rats tail. J Cancer Ther 2:325–33410.4236/jct.2011.23045 ↗
74. Wanga M, Thanoua M (2010) Targeting nanoparticles to cancer. Pharmacol Res 62:90–9910.1016/j.phrs.2010.03.005 ↗
75. Washington C (1990) Drug release from micro disperse system. A critical review. Int J Pharm 58:1–1210.1016/0378-5173(90)90280-H ↗
76. Win KY, Feng SS (2005) Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials 26:2713–272210.1016/j.biomaterials.2004.07.050 ↗
77. Yoo HS, Park TG (2001) Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA–PEG block copolymer. J Control Release 70:63–7010.1016/S0168-3659(00)00340-0 ↗
78. Yoo HS, Oh JE, Lee KH, Park TG (1999) Biodegradable nanoparticles containing doxorubicin-PLGA conjugate for sustained release. Pharm Res 16:1114–111810.1023/A:1018908421434 ↗
79. Yu T, Wang YY, Yang M, Schneider C, Zhong W, Pulicare S, Choi WJ, Mert O, Fu J, Lai SK, Hanes J (2012) Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid). Drug Deliv Transl Res 2:124–12810.1007/s13346-011-0048-9 ↗
80. Zambaux MF, Bonneaux F, Gref R, Maincent P, Dellacherie E, Alonso MJ, Labrude P (1998) Influence of experimental parameters on the characteristic of poly(lactic acid) nanoparticles prepared by a double emulsion method. J Control Release 50:31–4010.1016/S0168-3659(97)00106-5 ↗
81. Zhao H, Yung LYL (2007) Selectivity of folate conjugated polymer micelles against different tumor cells. Int J Pharm 349:256–26810.1016/j.ijpharm.2007.07.040 ↗
82. Zimmer A, Kreuter J, Robinson JR (1991) Influence of charged molecules on the zeta potential of PBCA nanoparticles. Proc Int Symp Control Release Bioact Mater 18:642–643