Environmental Chemistry Letters

, Volume 17, Issue 3, pp 1237–1249 | Cite as

Antimicrobial therapeutics delivery systems based on biodegradable polylactide/polylactide-co-glycolide particles

  • Robin Kumar
  • Divya Jha
  • Amulya K. PandaEmail author


Infectious diseases are globally associated with high mortality in spite of the availability of therapeutic agents against most pathogenic microorganisms. This is due to the emergence of new infectious diseases and novel pathogen strategies to evade host defenses. There is thus a need to develop potent therapeutics and techniques for effective delivery of vaccines and drugs. Particles based on poly(lactic acid) and poly(lactic-co-glycolic acid) polymer-based particles are suitable delivery systems due to their biodegradable and biocompatible nature. They can be tailored to display various properties such as sustained release, dose sparing, bioactivity maintenance and targeted delivery. This review focuses on polymeric particle-based delivery systems to develop novel vaccines or drugs. Cellular interactions of particulate systems and the mechanism of action in animal models are also discussed.


Infectious diseases Therapeutic agents Biodegradable polymer Polymeric particle Delivery system 



The authors are grateful to the National Institute of Immunology for financial support.

Authors’ contributions

Robin Kumar and Divya Jha have an equal contribution to this work, and all authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interests.


  1. Admane P, Gupta J, Ancy I, Kumar R, Panda AK (2017) Design and evaluation of antibiotic releasing self-assembled scaffolds at room temperature using biodegradable polymer particles. Int J Pharm 520(1):284–296. CrossRefGoogle Scholar
  2. Agallou M, Margaroni M, Athanasiou E, Toubanaki DK, Kontonikola K, Karidi K, Kammona O, Kiparissides C, Karagouni E (2017) Identification of BALB/c immune markers correlated with a partial protection to leishmania infantum after vaccination with a rationally designed multi-epitope cysteine protease a peptide-based nanovaccine. PLoS Negl Trop Dis 11(1):e0005311. CrossRefGoogle Scholar
  3. Aldrian G, Vaissière A, Konate K, Seisel Q, Vivès E, Fernandez F, Viguier V, Genevois C, Couillaud F, Démèné H (2017) PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in vitro and in vivo. J Controll Release 256:79–91. CrossRefGoogle Scholar
  4. Allahyari M, Mohabati R, Amiri S, Rastaghi ARE, Babaie J, Mahdavi M, Vatanara A, Golkar M (2016) Synergistic effect of rSAG1 and rGRA2 antigens formulated in PLGA microspheres in eliciting immune protection against Toxoplasama gondii. Exp Parasitol 170:236–246. CrossRefGoogle Scholar
  5. Anderson JM, Shive MS (2012) Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 64:72–82. CrossRefGoogle Scholar
  6. Basu A, Kunduru KR, Doppalapudi S, Domb AJ, Khan W (2016) Poly(lactic acid) based hydrogels. Adv Drug Deliv Rev 107:192–205. CrossRefGoogle Scholar
  7. Brady JM, Cutright DE, Miller RA, Battistone GC, Hunsuck EE (1973) Resorption rate, route of elimination, and ultrastructure of the implant site of polylactic acid in the abdominal wall of the rat. J Biomed Mater Res Part A 7(2):155–166. CrossRefGoogle Scholar
  8. Bruno C, Agnolon V, Berti F, Bufali S, O’Hagan DT, Baudner BC (2016) The preparation and characterization of PLG nanoparticles with an entrapped synthetic TLR7 agonist and their preclinical evaluation as adjuvant for an adsorbed DTaP vaccine. Eur J Pharm Biopharm 105:1–8. CrossRefGoogle Scholar
  9. Cai H, Liang Z, Huang W, Wen L, Chen G (2017) Engineering PLGA nano-based systems through understanding the influence of nanoparticle properties and cell-penetrating peptides for cochlear drug delivery. Int J Pharm 532(1):55–65. CrossRefGoogle Scholar
  10. Carreño JM, Perez-Shibayama C, Gil-Cruz C, Printz A, Pastelin R, Isibasi A, Chariatte D, Tanoue Y, Lopez-Macias C, Gander B (2016) PLGA-microencapsulation protects Salmonella typhi outer membrane proteins from acidic degradation and increases their mucosal immunogenicity. Vaccine 34(35):4263–4269. CrossRefGoogle Scholar
  11. Chong CS, Cao M, Wong WW, Fischer KP, Addison WR, Kwon GS, Tyrrell DL, Samuel J (2005) Enhancement of T helper type 1 immune responses against hepatitis B virus core antigen by PLGA nanoparticle vaccine delivery. J Controll Release 102(1):85–99. CrossRefGoogle Scholar
  12. Coelho JF, Ferreira PC, Alves P, Cordeiro R, Fonseca AC, Góis JR, Gil MH (2010) Drug delivery systems: advanced technologies potentially applicable in personalized treatments. EPMA J 1(1):164–209. CrossRefGoogle Scholar
  13. Cruz J, Flórez J, Torres R, Urquiza M, Gutiérrez J, Guzmán F, Ortiz C (2017) Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or poly (lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157: H7 and methicillin resistant Staphylococcus aureus (MRSA). Nanotechnology 28(13):135102. CrossRefGoogle Scholar
  14. Dalzon B, Lebas C, Jimenez G, Gutjahr A, Terrat C, Exposito J-Y, Verrier B, Lethias C (2016) Poly (Lactic Acid) nanoparticles targeting α5β1 integrin as vaccine delivery vehicle, a prospective study. PLoS ONE 11(12):e0167663. CrossRefGoogle Scholar
  15. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Controll Release 161(2):505–522. CrossRefGoogle Scholar
  16. Dhakal S, Hiremath J, Bondra K, Lakshmanappa YS, Shyu D-L, Ouyang K, K-i Kang, Binjawadagi B, Goodman J, Tabynov K (2017) Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs. J Controll Release 247:194–205. CrossRefGoogle Scholar
  17. Du X, Wang J-L, Iqbal S, Li H, Cao Z, Wang Y-C, Du J, Wang J (2018) The effect of surface charge on oral absorption of polymeric nanoparticles. Biomater Sci 6(3):642–650. CrossRefGoogle Scholar
  18. Ekanem EE, Zhang Z, Vladisavljevic GT (2017a) Facile production of biodegradable bipolymer patchy and patchy Janus particles with controlled morphology by microfluidic routes. Langmuir 33(34):8476–8482. CrossRefGoogle Scholar
  19. Ekanem EE, Zhang Z, Vladisavljević GT (2017b) Facile microfluidic production of composite polymer core-shell microcapsules and crescent-shaped microparticles. J Colloid Interface Sci 498:387–394. CrossRefGoogle Scholar
  20. El-Hammadi MM, Delgado ÁV, Melguizo C, Prados JC, Arias JL (2017) Folic acid-decorated and PEGylated PLGA nanoparticles for improving the antitumour activity of 5-fluorouracil. Int J Pharm 516(1):61–70. CrossRefGoogle Scholar
  21. Fröhlich E (2012) The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomed 7:5577. CrossRefGoogle Scholar
  22. Gagliardi M, Bertero A, Bifone A (2017) Molecularly imprinted biodegradable nanoparticles. Sci Rep 7:40046. CrossRefGoogle Scholar
  23. Genta I, Colonna C, Conti B, Caliceti P, Salmaso S, Speziale P, Pietrocola G, Chiesa E, Modena T, Dorati R (2016) CNA-loaded PLGA nanoparticles improve humoral response against S. aureus-mediated infections in a mouse model: subcutaneous vs. nasal administration strategy. J Microencapsul 33(8):750–762CrossRefGoogle Scholar
  24. Gourdon B, Chemin C, Moreau A, Arnauld T, Baumy P, Cisternino S, Péan J-M, Declèves X (2017) Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir. Int J Pharm 529(1–2):357–370. CrossRefGoogle Scholar
  25. Gregory AE, Titball R, Williamson D (2013) Vaccine delivery using nanoparticles. Front Cell Infect Microbiol 3:13. CrossRefGoogle Scholar
  26. Gutierro I, Hernandez R, Igartua M, Gascon A, Pedraz J (2002) Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine 21(1):67–77. CrossRefGoogle Scholar
  27. Gutjahr A, Phelip C, Coolen A-L, Monge C, Boisgard A-S, Paul S, Verrier B (2016) Biodegradable polymeric nanoparticles-based vaccine adjuvants for lymph nodes targeting. Vaccines 4(4):34. CrossRefGoogle Scholar
  28. Hillaireau H, Couvreur P (2009) Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci 66(17):2873–2896. CrossRefGoogle Scholar
  29. Hiremath J, K-i Kang, Xia M, Elaish M, Binjawadagi B, Ouyang K, Dhakal S, Arcos J, Torrelles JB, Jiang X (2016) Entrapment of H1N1 influenza virus derived conserved peptides in PLGA nanoparticles enhances T cell response and vaccine efficacy in pigs. PLoS ONE 11(4):e0151922. CrossRefGoogle Scholar
  30. James R, Manoukian OS, Kumbar SG (2016) Poly (lactic acid) for delivery of bioactive macromolecules. Adv Drug Deliv Rev 107:277–288. CrossRefGoogle Scholar
  31. Johansen P, Men Y, Merkle HP, Gander B (2000) Revisiting PLA/PLGA microspheres: an analysis of their potential in parenteral vaccination. Eur J Pharm Biopharm 50(1):129–146. CrossRefGoogle Scholar
  32. Kasturi SP, Kozlowski PA, Nakaya HI, Burger MC, Russo P, Pham M, Kovalenkov Y, Silveira EL, Havenar-Daughton C, Burton SL (2017) Adjuvanting a simian immunodeficiency virus vaccine with toll-like receptor ligands encapsulated in nanoparticles induces persistent antibody responses and enhanced protection in TRIM5α restrictive macaques. J Virol 91(4):e01844. CrossRefGoogle Scholar
  33. Kumar R, Jha D, Panda AK (2019) Polylactide/polylactide-co-glycolide-based delivery system for bioactive compounds against microbes. Pharm Microbes. CrossRefGoogle Scholar
  34. Li P, Asokanathan C, Liu F, Khaing KK, Kmiec D, Wei X, Song B, Xing D, Kong D (2016) PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model. Int J Pharm 513(1):183–190. CrossRefGoogle Scholar
  35. Liu L, Ma P, Wang H, Zhang C, Sun H, Wang C, Song C, Leng X, Kong D, Ma G (2016) Immune responses to vaccines delivered by encapsulation into and/or adsorption onto cationic lipid-PLGA hybrid nanoparticles. J Controll Release 225:230–239. CrossRefGoogle Scholar
  36. Marasini N, Khalil ZG, Giddam AK, Ghaffar KA, Hussein WM, Capon RJ, Batzloff MR, Good MF, Skwarczynski M, Toth I (2016) Lipid core peptide/poly (lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus. Int J Pharm 513(1):410–420. CrossRefGoogle Scholar
  37. Margaroni M, Agallou M, Kontonikola K, Karidi K, Kammona O, Kiparissides C, Gaitanaki C, Karagouni E (2016) PLGA nanoparticles modified with a TNFα mimicking peptide, soluble Leishmania antigens and MPLA induce T cell priming in vitro via dendritic cell functional differentiation. Eur J Pharm Biopharm 105:18–31. CrossRefGoogle Scholar
  38. Metz SW, Tian S, Hoekstra G, Yi X, Stone M, Horvath K, Miley MJ, DeSimone J, Luft CJ, de Silva AM (2016) Precisely molded nanoparticle displaying DENV-E proteins induces robust serotype-specific neutralizing antibody responses. PLoS Negl Trop Dis 10(10):e0005071. CrossRefGoogle Scholar
  39. Mitragotri S, Burke PA, Langer R (2014) Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat Rev Drug Discov 13(9):655. CrossRefGoogle Scholar
  40. Murariu M, Dubois P (2016) PLA composites: from production to properties. Adv Drug Deliv Rev 107:17–46. CrossRefGoogle Scholar
  41. Nabi H, Rashid I, Ahmad N, Durrani A, Akbar H, Islam S, Bajwa AA, Shehzad W, Ashraf K, Imran N (2017) Induction of specific humoral immune response in mice immunized with ROP18 nanospheres from Toxoplasma gondii. Parasitol Res 116(1):359–370. CrossRefGoogle Scholar
  42. Oyewumi MO, Kumar A, Cui Z (2010) Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Expert Rev Vaccines 9(9):1095–1107. CrossRefGoogle Scholar
  43. Pagels RF, Prud’homme RK (2015) Polymeric nanoparticles and microparticles for the delivery of peptides, biologics, and soluble therapeutics. J Controll Release 219:519–535. CrossRefGoogle Scholar
  44. Pandey SK, Patel DK, Maurya AK, Thakur R, Mishra DP, Vinayak M, Haldar C, Maiti P (2016) Controlled release of drug and better bioavailability using poly (lactic acid-co-glycolic acid) nanoparticles. Int J Biol Macromol 89:99–110. CrossRefGoogle Scholar
  45. Panyam J, Labhasetwar V (2003) Dynamics of endocytosis and exocytosis of poly (d, l-lactide-co-glycolide) nanoparticles in vascular smooth muscle cells. Pharm Res 20(2):212–220. CrossRefGoogle Scholar
  46. Panyam J, Zhou W-Z, Prabha S, Sahoo SK, Labhasetwar V (2002) Rapid endo-lysosomal escape of poly (d, l-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J 16(10):1217–1226. CrossRefGoogle Scholar
  47. Pei Y, Mohamed MF, Seleem MN, Yeo Y (2017) Particle engineering for intracellular delivery of vancomycin to methicillin-resistant Staphylococcus aureus (MRSA)-infected macrophages. J Controll Release 267:133. CrossRefGoogle Scholar
  48. Peres C, Matos AI, Conniot J, Sainz V, Zupančič E, Silva JM, Graça L, Gaspar RS, Préat V, Florindo HF (2017) Poly (lactic acid)-based particulate systems are promising tools for immune modulation. Acta Biomater 48:41–57. CrossRefGoogle Scholar
  49. Peyre M, Audran R, Estevez F, Corradin G, Gander B, Sesardic D, Johansen P (2004) Childhood and malaria vaccines combined in biodegradable microspheres produce immunity with synergistic interactions. J Controll Release 99(3):345–355. CrossRefGoogle Scholar
  50. Qu S, Zhao L, Zhu J, Wang C, Dai C, Guo H, Hao Z (2017) Preparation and testing of cefquinome-loaded poly lactic-co-glycolic acid microspheres for lung targeting. Drug Deliv 24(1):745–751. CrossRefGoogle Scholar
  51. Raudszus B, Mulac D, Langer K (2018) A new preparation strategy for surface modified PLA nanoparticles to enhance uptake by endothelial cells. Int J Pharm 536(1):211–221. CrossRefGoogle Scholar
  52. Roointan A, Kianpour S, Memari F, Gandomani M, Gheibi Hayat SM, Mohammadi-Samani S (2018) Poly (lactic-co-glycolic acid): the most ardent and flexible candidate in biomedicine! Int J Polym Mater Polym Biomater 67:1028. CrossRefGoogle Scholar
  53. Roopngam P, Liu K, Mei L, Zheng Y, Zhu X, Tsai H-I, Huang L (2016) Hepatitis C virus E2 protein encapsulation into poly d, l-lactic-co-glycolide microspheres could induce mice cytotoxic T-cell response. Int J Nanomed 11:5361. CrossRefGoogle Scholar
  54. Saffer EM, Tew GN, Bhatia SR (2011) Poly (lactic acid)-poly (ethylene oxide) block copolymers: new directions in self-assembly and biomedical applications. Curr Med Chem 18(36):5676–5686. CrossRefGoogle Scholar
  55. Sahin A, Esendagli G, Yerlikaya F, Caban-Toktas S, Yoyen-Ermis D, Horzum U, Aktas Y, Khan M, Couvreur P, Capan Y (2017) A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles’ characteristics and efficacy of intracellular delivery. Artif Cells Nanomed Biotechnol 45:1657. CrossRefGoogle Scholar
  56. Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L (2016) Nanoparticle-mediated brain drug delivery: overcoming blood–brain barrier to treat neurodegenerative diseases. J Controll Release 235:34–47. CrossRefGoogle Scholar
  57. Seok H, Noh JY, Lee DY, Kim SJ, Song CS, Kim YC (2017) Effective humoral immune response from a H1N1 DNA vaccine delivered to the skin by microneedles coated with PLGA-based cationic nanoparticles. J Controll Release 265:66–74. CrossRefGoogle Scholar
  58. Shah RR, O’Hagan DT, Amiji MM, Brito LA (2014) The impact of size on particulate vaccine adjuvants. Nanomedicine 9(17):2671–2681. CrossRefGoogle Scholar
  59. Silva A, Soema P, Slütter B, Ossendorp F, Jiskoot W (2016) PLGA particulate delivery systems for subunit vaccines: linking particle properties to immunogenicity. Hum Vaccines Immunother 12(4):1056–1069. CrossRefGoogle Scholar
  60. Steinbach JM, Seo Y-E, Saltzman WM (2016) Cell penetrating peptide-modified poly (lactic-co-glycolic acid) nanoparticles with enhanced cell internalization. Acta Biomater 30:49–61. CrossRefGoogle Scholar
  61. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM (2016) PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 99:28–51. CrossRefGoogle Scholar
  62. Sun Z, Yan X, Liu Y, Huang L, Kong C, Qu X, Wang M, Gao R, Qin H (2017) Application of dual targeting drug delivery system for the improvement of anti-glioma efficacy of doxorubicin. Oncotarget 8(35):58823. CrossRefGoogle Scholar
  63. Tan Z, Liu W, Liu H, Li C, Zhang Y, Meng X, Tang T, Xi T, Xing Y (2017) Oral Helicobacter pylori vaccine-encapsulated acid-resistant HP55/PLGA nanoparticles promote immune protection. Eur J Pharm Biopharm 111:33–43. CrossRefGoogle Scholar
  64. Thomas N, Thorn C, Richter K, Thierry B, Prestidge C (2016) Efficacy of poly-lactic-co-glycolic acid micro-and nanoparticles of ciprofloxacin against bacterial biofilms. J Pharm Sci 105(10):3115–3122. CrossRefGoogle Scholar
  65. Tran TH, Tran TTP, Nguyen HT, Dai Phung C, Jeong J-H, Stenzel MH, Jin SG, Yong CS, Truong DH, Kim JO (2018) Nanoparticles for dendritic cell-based immunotherapy. Int J Pharm. CrossRefGoogle Scholar
  66. Türeli NG, Torge A, Juntke J, Schwarz BC, Schneider-Daum N, Türeli AE, Lehr C-M, Schneider M (2017) Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections. Eur J Pharm Biopharm 117:363–371. CrossRefGoogle Scholar
  67. Tzeng SY, Guarecuco R, McHugh KJ, Rose S, Rosenberg EM, Zeng Y, Langer R, Jaklenec A (2016) Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release. J Controll Release 233:101–113. CrossRefGoogle Scholar
  68. Vasir JK, Labhasetwar V (2007) Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev 59(8):718–728. CrossRefGoogle Scholar
  69. Wan F, Yang M (2016) Design of PLGA-based depot delivery systems for biopharmaceuticals prepared by spray drying. Int J Pharm 498(1):82–95. CrossRefGoogle Scholar
  70. Wang Q, Barry MA, Seid CA, Hudspeth EM, McAtee CP, Heffernan MJ (2017) 3M–052 as an adjuvant for a PLGA microparticle-based Leishmania donovani recombinant protein vaccine. J Biomed Mater Res B Appl Biomater 106:1587. CrossRefGoogle Scholar
  71. Watkins HC, Pagan CL, Childs HR, Posada S, Chau A, Rios J, Guarino C, DeLisa MP, Whittaker GR, Putnam D (2017) A single dose and long lasting vaccine against pandemic influenza through the controlled release of a heterospecies tandem M2 sequence embedded within detoxified bacterial outer membrane vesicles. Vaccine 35:5373. CrossRefGoogle Scholar
  72. Yang HW, Ye L, Guo XD, Yang C, Compans RW, Prausnitz MR (2017) Ebola vaccination using a DNA vaccine coated on PLGA-PLL/γPGA Nanoparticles administered using a microneedle patch. Adv Healthc Mater 6(1):1600750. CrossRefGoogle Scholar
  73. Zhang N-Z, Xu Y, Wang M, Chen J, Huang S-Y, Gao Q, Zhu X-Q (2016) Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly (lactide-co-glycolide) microspheres induces long-term protective immunity in mice. BMC Infect Dis 16(1):168. CrossRefGoogle Scholar
  74. Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y (2011) Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 7(10):1322–1337. CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Product Development Cell-IINational Institute of ImmunologyNew DelhiIndia

Personalised recommendations