Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Applied Polymer Science
  4. Volume 7, Issue 1
  5. Article
Volume 7, Issue 1
  • ISSN: 2452-2716
  • E-ISSN: 2452-2724

Abstract

Background

Poly(lactic--glycolic acid) (PLGA), an FDA-approved copolymer, is widely recognized for its biocompatibility, biodegradability, and versatility in drug delivery systems. Despite its advantages, challenges, such as poor drug loading and burst release, motivate the exploration of innovative modifications. The current research aimed to modify the linear PLGA to lipoyl ester terminated star PLGA polymer to minimize initial burst release by increasing the molecular weight and fabricate risperidone-loaded microspheres.

Methods

In this study, we have presented a novel approach involving the synthesis of star PLGA through the direct melt polycondensation of PLGA with pentaerythritol, followed by conjugation with lipoic acid to form lipoyl ester terminated star PLGA. Structural confirmation was done by Fourier Transform Infrared spectroscopy (FT-IR), proton Nuclear Magnetic Resonance (1H-NMR), and Gel Permeation Chromatography (GPC). Microspheres were fabricated from lipoyl ester terminated star PLGA and characterized for their particle size and surface morphology by Scanning Electron Microscopy (SEM) and drug release by dialysis bag method.

Results

The results of the study have indicated successful conjugation of lipoic acid to star PLGA forming lipoyl ester terminated star PLGA, as confirmed by FT-IR, 1H-NMR, and GPC analyses. Microspheres developed from the synthesized polymer exhibited particle sizes ranging from 4.64 μm to 11.7 μm and demonstrated sustained drug delivery, with 99.8% release over 45 d, in contrast to the plain drug that achieved complete dissolution within 3 h.

Conclusion

The resulting material has demonstrated unique bioresponsive and multifunctional properties, with evidence of successful synthesis provided through comprehensive characterization techniques, and suitability for the fabrication of microspheres for sustained drug delivery systems.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/caps/10.2174/0124522716306935240614081407
2024-06-21
2025-06-23

  • From This Site

    /content/journals/caps/10.2174/0124522716306935240614081407
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MakadiaH.K. SiegelS.J. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier.Polymers2011331377139710.3390/polym303137722577513
     [Google Scholar]
  2. KapoorD.N. BhatiaA. KaurR. SharmaR. KaurG. DhawanS. PLGA: A unique polymer for drug delivery.Ther. Deliv.201561415810.4155/tde.14.9125565440
     [Google Scholar]
  3. MirM. AhmedN. RehmanA. Recent applications of PLGA based nanostructures in drug delivery.Colloids Surf. B Biointerfaces201715921723110.1016/j.colsurfb.2017.07.03828797972
     [Google Scholar]
  4. PerinelliD.R. CespiM. BonacucinaG. PalmieriG.F. PEGylated polylactide (PLA) and poly (lactic-co-glycolic acid) (PLGA) copolymers for the design of drug delivery systems.J. Pharm. Investig.201949444345810.1007/s40005‑019‑00442‑2
     [Google Scholar]
  5. AsteteC.E. SabliovC.M. Synthesis and characterization of PLGA nanoparticles.J. Biomater. Sci. Polym. Ed.200617324728910.1163/15685620677599732216689015
     [Google Scholar]
  6. MüllerM. VörösJ. CsúcsG. Surface modification of PLGA microspheres.J. Biomed. Mater. Res. A200366A1556110.1002/jbm.a.1050212833431
     [Google Scholar]
  7. JainR.A. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices.Biomaterials200021232475249010.1016/S0142‑9612(00)00115‑011055295
     [Google Scholar]
  8. MartinsC. SousaF. AraújoF. SarmentoB. Functionalizing PLGA and PLGA derivatives for drug delivery and tissue regeneration applications.Adv. Healthc. Mater.201871170103510.1002/adhm.20170103529171928
     [Google Scholar]
  9. BalaI. HariharanS. KumarM.R. PLGA nanoparticles in drug delivery: The state of the art.Crit. Rev. Ther. Drug Carrier Syst.200421538742210.1615/CritRevTherDrugCarrierSyst.v21.i5.20
     [Google Scholar]
  10. SharmaS. ParmarA. KoriS. SandhirR. PLGA-based nanoparticles: A new paradigm in biomedical applications.Trends Analyt. Chem.201680304010.1016/j.trac.2015.06.014
     [Google Scholar]
  11. El-HammadiM.M. AriasJ.L. Recent advances in the surface functionalization of PLGA-based nanomedicines.Nanomaterials202212335410.3390/nano1203035435159698
     [Google Scholar]
  12. TangZ. HeC. TianH. Polymeric nanostructured materials for biomedical applications.Prog. Polym. Sci.2016608612810.1016/j.progpolymsci.2016.05.005
     [Google Scholar]
  13. KamalyN. YameenB. WuJ. FarokhzadO.C. Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release.Chem. Rev.201611642602266310.1021/acs.chemrev.5b0034626854975
     [Google Scholar]
  14. ZhangY. ChanH.F. LeongK.W. Advanced materials and processing for drug delivery: The past and the future.Adv. Drug Deliv. Rev.201365110412010.1016/j.addr.2012.10.00323088863
     [Google Scholar]
  15. OkamotoM. JohnB. Synthetic biopolymer nanocomposites for tissue engineering scaffolds.Prog. Polym. Sci.20133810-111487150310.1016/j.progpolymsci.2013.06.001
     [Google Scholar]
  16. PagelsR.F. Prud’hommeR.K. Polymeric nanoparticles and microparticles for the delivery of peptides, biologics, and soluble therapeutics.J. Control. Release201521951953510.1016/j.jconrel.2015.09.00126359125
     [Google Scholar]
  17. HrkachJ. Von HoffD. AliM.M. Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile.Sci. Transl. Med.20124128128ra3910.1126/scitranslmed.300365122491949
     [Google Scholar]
  18. RezvantalabS. DrudeN.I. MoravejiM.K. PLGA-based nanoparticles in cancer treatment.Front. Pharmacol.20189126010.3389/fphar.2018.0126030450050
     [Google Scholar]
  19. ChatterjeeM. ChandaN. Formulation of PLGA nano-carriers: specialized modification for cancer therapeutic applications.Mat Adv20223283785810.1039/D1MA00600B
     [Google Scholar]
  20. Von HoffD.D. MitaM.M. RamanathanR.K. Phase I study of PSMA-targeted docetaxel-containing nanoparticle BIND-014 in patients with advanced solid tumors.Clin. Cancer Res.201622133157316310.1158/1078‑0432.CCR‑15‑254826847057
     [Google Scholar]
  21. AndersonJ.M. ShiveM.S. Biodegradation and biocompatibility of PLA and PLGA microspheres.Adv. Drug Deliv. Rev.199728152410.1016/S0169‑409X(97)00048‑310837562
     [Google Scholar]
  22. ParkK. Isolated lung model for assessing drug absorption from PLGA microparticles.J. Control. Release201622626810.1016/j.jconrel.2016.03.00326987271
     [Google Scholar]
  23. DoppalapudiS. JainA. DombA.J. KhanW. Biodegradable polymers for targeted delivery of anti-cancer drugs.Expert Opin. Drug Deliv.201613689190910.1517/17425247.2016.115667126983898
     [Google Scholar]
  24. LiuJ. LiM. LuoZ. DaiL. GuoX. CaiK. Design of nanocarriers based on complex biological barriers in vivo for tumor therapy.Nano Today201715569010.1016/j.nantod.2017.06.010
     [Google Scholar]
  25. LiK. LiuB. Polymer-encapsulated organic nanoparticles for fluorescence and photoacoustic imaging.Chem. Soc. Rev.201443186570659710.1039/C4CS00014E24792930
     [Google Scholar]
  26. RatzingerG. FillaferC. KerletaV. WirthM. GaborF. The role of surface functionalization in the design of PLGA micro-and nanoparticles.Crit. Rev. Ther. Drug Carrier Syst.201011010.1615/CritRevTherDrugCarrierSyst.v27.i1.10
     [Google Scholar]
  27. GaoW. ZhangL. Engineering red‐blood‐cell‐membrane–coated nanoparticles for broad biomedical applications.AIChE J.201561373874610.1002/aic.14735
     [Google Scholar]
  28. FangR.H. HuC.M.J. LukB.T. Cancer cell membrane-coated nanoparticles for anticancer vaccination and drug delivery.Nano Lett.20141442181218810.1021/nl500618u24673373
     [Google Scholar]
  29. WuJ. ZhangJ. DengC. MengF. ZhongZ. Vitamin E-Oligo (methyl diglycol l-glutamate) as a biocompatible and functional surfactant for facile preparation of active tumor-targeting PLGA nanoparticles.Biomacromolecules20161772367237410.1021/acs.biomac.6b0038027305935
     [Google Scholar]
  30. LiuL. CaoF. LiuX. Hyaluronic acid-modified cationic lipid–PLGA hybrid nanoparticles as a nanovaccine induce robust humoral and cellular immune responses.ACS Appl. Mater. Interfaces2016819119691197910.1021/acsami.6b0113527088457
     [Google Scholar]
  31. WangH. AgarwalP. ZhaoS. Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells.Biomaterials201572748910.1016/j.biomaterials.2015.08.04826344365
     [Google Scholar]
  32. WafaE.I. GearyS.M. RossK.A. GoodmanJ.T. NarasimhanB. SalemA.K. Pentaerythritol-based lipid A bolsters the antitumor efficacy of a polyanhydride particle-based cancer vaccine.Nanomedicine20192110205510.1016/j.nano.2019.10205531319179
     [Google Scholar]
  33. BeigA. FengL. WalkerJ. Physical–chemical characterization of octreotide encapsulated in commercial glucose-star PLGA microspheres.Mol. Pharm.202017114141415110.1021/acs.molpharmaceut.0c0061932876463
     [Google Scholar]
  34. ZhangJ. TaoW. ChenY. Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E TPGS nanoparticles for lung cancer therapy.J. Mater. Sci. Mater. Med.201526416510.1007/s10856‑015‑5498‑z25791459
     [Google Scholar]
  35. TaoW. ZengX. LiuT. Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy.Acta Biomater.20139118910892010.1016/j.actbio.2013.06.03423816645
     [Google Scholar]
  36. ZengX. TaoW. MeiL. HuangL. TanC. FengS.S. Cholic acid-functionalized nanoparticles of star-shaped PLGA-vitamin E TPGS copolymer for docetaxel delivery to cervical cancer.Biomaterials201334256058606710.1016/j.biomaterials.2013.04.05223694904
     [Google Scholar]
  37. WuY. WangZ. LiuG. Novel simvastatin-loaded nanoparticles based on cholic acid-core star-shaped PLGA for breast cancer treatment.J. Biomed. Nanotechnol.20151171247126010.1166/jbn.2015.206826307847
     [Google Scholar]
  38. DavaranS. OmidiY. AnzabiM. Preparation and in vitro evaluation of linear and star-branched PLGA nanoparticles for insulin delivery.J. Bioact. Compat. Polym.200823211513110.1177/0883911507088276
     [Google Scholar]
  39. ParkK. SkidmoreS. HadarJ. Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation.J. Control. Release201930412513410.1016/j.jconrel.2019.05.00331071374
     [Google Scholar]
  40. WuB. LiangY. TanY. Genistein-loaded nanoparticles of star-shaped diblock copolymer mannitol-core PLGA–TPGS for the treatment of liver cancer.Mater. Sci. Eng. C20165979280010.1016/j.msec.2015.10.08726652434
     [Google Scholar]
  41. BeigA. AckermannR. WangY. SchutzmanR. SchwendemanS.P. Minimizing the initial burst of octreotide acetate from glucose star PLGA microspheres prepared by the solvent evaporation method.Int. J. Pharm.202262412184210.1016/j.ijpharm.2022.12184235609832
     [Google Scholar]
  42. SnejdrovaE. PodzimekS. MartiskaJ. HolasO. DittrichM. Branched PLGA derivatives with tailored drug delivery properties.Acta Pharm.2020701637510.2478/acph‑2020‑001131677370
     [Google Scholar]
  43. OuyangC. LiuQ. ZhaoS. MaG. ZhangZ. SongC. Synthesis and characterization of star-shaped poly (lactide-co-glycolide) and its drug-loaded microspheres.Polym. Bull.2012681273610.1007/s00289‑011‑0516‑x
     [Google Scholar]
  44. LeeS.J. ParkC.W. KimS.C. Temperature-sensitive sol-gel transition behavior of biodegradable four-arm star-shaped PEG-PLGA block copolymer aqueous solution.Polym. J.200941542543110.1295/polymj.PJ2008164
     [Google Scholar]
  45. ChongY.K. ZainolI. NgC.H. OoiI.H. Miktoarm star polymers nanocarrier: Synthesis, characterization, and in-vitro drug release study.J. Polym. Res.20192637910.1007/s10965‑019‑1726‑4
     [Google Scholar]
  46. TengL NieW ZhouY SongL ChenP Synthesis and characterization of star‐shaped PLLA with sorbitol as core and its microspheres application in controlled drug release.J Appl Polym Sci201513227app.4221310.1002/app.42213
     [Google Scholar]
  47. KoufakiM. DetsiA. KiziridiC. Multifunctional lipoic acid conjugates.Curr. Med. Chem.200916354728474210.2174/09298670978987827419903137
     [Google Scholar]
  48. HajibabazadehS. GhalehH. AbbasiF. ForoutaniK. Design of thermo-responsive cell culture dishes using poly(N-isopropylacrylamide)-block-polystyrene copolymers for cell sheet technology.Eur. Polym. J.202319511223110.1016/j.eurpolymj.2023.112231
     [Google Scholar]
  49. GuptaC. SinghP. VaidyaS. AmbreP. CoutinhoE. A novel thermoresponsive nano carrier matrix of hyaluronic acid, methotrexate and chitosan to target the cluster of differentiation 44 receptors in tumors.Int. J. Biol. Macromol.202324312523810.1016/j.ijbiomac.2023.12523837290545
     [Google Scholar]
  50. GuptaC. NaikI. MenonM. AmbreP. CoutinhoE. A review on exploring the opportunities of polymer drug conjugated systems for targeted cancer treatment.Curr. Drug Deliv.202220183035400344
     [Google Scholar]
  51. GuptaC. UthaleA. TeniT. AmbreP. CoutinhoE. Emerging polymer-based nanomaterials for cancer therapeutics.Nanotechnology in the Life Sciences2021118922910.1007/978‑3‑030‑74330‑7_7
     [Google Scholar]
  52. ChuD. TianJ. LiuW. LiZ. LiY. Poly(lactic-co-glycolic acid) microspheres for the controlled release of huperzine A: in vitro and in vivo studies and the application in the treatment of the impaired memory of mice.Chem. Pharm. Bull.200755462562810.1248/cpb.55.62517409558
     [Google Scholar]
  53. SuZ. SunF. ShiY. Effects of formulation parameters on encapsulation efficiency and release behavior of risperidone poly(D,L-lactide-co-glycolide) microsphere.Chem. Pharm. Bull.200957111251125610.1248/cpb.57.125119881277
     [Google Scholar]
  54. Al-KassasR. Design and in vitro evaluation of gentamicin–eudragit microspheres intended for intra-ocular administration.J. Microencapsul.2004211718110.1080/0265204031000161999214718187
     [Google Scholar]
  55. GaoL. ZhangD. ChenM. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system.J. Nanopart. Res.200810584586210.1007/s11051‑008‑9357‑4
     [Google Scholar]
  56. LiuW.H. SongJ.L. LiuK. ChuD.F. LiY.X. Preparation and in vitro and in vivo release studies of huperzine a loaded microspheres for the treatment of Alzheimer’s disease.J. Control. Release2005107341742710.1016/j.jconrel.2005.03.02516154224
     [Google Scholar]
  57. BerklandC. KipperM.J. NarasimhanB. KimK.K. PackD.W. Microsphere size, precipitation kinetics and drug distribution control drug release from biodegradable polyanhydride microspheres.J. Control. Release200494112914110.1016/j.jconrel.2003.09.01114684277
     [Google Scholar]
  58. KohnoM. AndhariyaJ.V. WanB. The effect of PLGA molecular weight differences on risperidone release from microspheres.Int. J. Pharm.202058211933910.1016/j.ijpharm.2020.11933932305366
     [Google Scholar]
  59. D’SouzaS. FarajJ.A. GiovagnoliS. DeLucaP.P. Development of risperidone PLGA microspheres.J. Drug Deliv.2014201462046410.1155/2014/620464
     [Google Scholar]
  60. MohammadpourF. KamaliH. HadizadehF. The PLGA microspheres synthesized by a thermosensitive hydrogel emulsifier for sustained release of risperidone.J. Pharm. Innov.202117513
     [Google Scholar]
  61. HuX. ZhangJ. TangX. An accelerated release method of risperidone loaded PLGA microspheres with good IVIVC.Curr. Drug Deliv.2018151879628521697
     [Google Scholar]
  62. AukunuruJ. YerraguntaB. JogalaS. ChinnalaK.M. Development of a novel 3-month drug releasing risperidone microspheres.J. Pharm. Bioallied Sci.201571374410.4103/0975‑7406.14877725709335
     [Google Scholar]
  63. ZhaoJ. WangL. FanC. Development of near zero-order release PLGA-based microspheres of a novel antipsychotic.Int. J. Pharm.20175161-2323810.1016/j.ijpharm.2016.11.00727825865
     [Google Scholar]
  64. JafarifarE. HajialyaniM. AkbariM. RahimiM. ShokoohiniaY. FattahiA. Preparation of a reproducible long-acting formulation of risperidone-loaded PLGA microspheres using microfluidic method.Pharm. Dev. Technol.201722683684310.1080/10837450.2016.122142627494230
     [Google Scholar]
  65. HuZ. LiuY. YuanW. WuF. SuJ. JinT. Effect of bases with different solubility on the release behavior of risperidone loaded PLGA microspheres.Colloids Surf. B Biointerfaces201186120621110.1016/j.colsurfb.2011.03.04321524893
     [Google Scholar]
  66. HuangZ. ChenX. FuH. Formation mechanism and in vitro evaluation of risperidone-containing PLGA microspheres fabricated by ultrafine particle processing system.J. Pharm. Sci.2017106113363337110.1016/j.xphs.2017.07.01028736289
     [Google Scholar]
  67. WangX. ChengR. ChengL. ZhongZ. Lipoyl ester terminated star PLGA as a simple and smart material for controlled drug delivery application.Biomacromolecules20181941368137310.1021/acs.biomac.8b0013029553255
     [Google Scholar]
  68. KhoeeS. RahmatolahzadehR. Synthesis and characterization of pH-responsive and folated nanoparticles based on self-assembled brush-like PLGA/PEG/AEMA copolymer with targeted cancer therapy properties: A comprehensive kinetic study.Eur. J. Med. Chem.20125041642710.1016/j.ejmech.2012.02.02722397922
     [Google Scholar]
/content/journals/caps/10.2174/0124522716306935240614081407
Loading
Design, Synthesis, and Evaluation of Lipoyl Ester Conjugated Star PLGA for Sustained Drug Delivery Systems
Curr Appl Polym Sci 7, 33 (2024); https://doi.org/10.2174/0124522716306935240614081407
/content/journals/caps/10.2174/0124522716306935240614081407
/content/journals/caps/10.2174/0124522716306935240614081407
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): copolymer; FT-IR; lipoyl ester terminated star PLGA; Poly(lactic-co-glycolic acid); star PLGA; tissue engineering

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test