Skip to main content
SpringerLink
Log in

Development of a PLGA-Nanosphere DDS Prepared by Spherical Crystallization with a Polymer

  • Chapter
  • First Online:
Spherical Crystallization as a New Platform for Particle Design Engineering

  • 313 Accesses

Abstract

In this chapter, we developed biocompatible and biodegradable polymeric micro/nanospheres using PLGA, loaded with a bioactive substance to create new, functional, next-generation medical systems. According to the physicochemical properties of the API with the solvent (e.g., wettability), two conceptually different methods, namely Emulsion Solvent Diffusion (ESD) and Phase Separation (PS), were developed to improve the pay load of the API with the resulting nanospheres. With a hydrophilic or water-soluble API, a chlorinated hydrocarbon and alcohol mixture was chosen as a good solvent for PLGA and a drug dispersed in an aqueous medium for the preparation of microspheres. For the preparation of nanospheres, the chlorinated hydrocarbon was eliminated from the process and acetone was introduced with alcohol to increase the diffusion rate of the water-soluble solvent and the turbulence of the interface of the emulsion droplet, resulting in spontaneous droplet formation. This process is known as ESD in water. With the PS method, the aqueous drug solution is dispersed in a dichloromethane–acetone mixture containing dissolved PLGA and span with a high shearing homogenizer to form a w/o emulsion. The addition of triester oil containing HGCR into the dispersing medium under stirring induces the PS of PLGA enclosing the drug. The drug-release behavior from the obtained nanospheres strongly depends on the preparation process. It is difficult to formulate nanospheres for direct use due to their strong aggregation tendency. To overcome this problem, the PLGA nanospheres are transformed into solid, dispersed nanosphere composites with a water-soluble excipient like a sugar alcohol, which can reproduce original nanospheres dispersed at applied site. Preparing nanocomposite particles cannot only improve the storage stability of the nanospheres but also allows handling them in the same way for preparing solid-dosage forms, such as tablets, capsules, DPIs, and so on. Colloidal polymeric nanospheres are closely coalesced and fused at the contact point of the particles, resulting in the formation of a film when water is removed by heating. Biodegradable PLGA films can be prepared to approach for a new biodegradable depot system. Surface-modified PLGA NSs with chitosan can improve drug absorption at the target site due to a sustained stay and prolonged release of the drug. Oral administration of calcitonin–PLGA NS modified with chitosan to rats significantly reduced the calcium level in blood as compared to a calcitonin solution, and the reducing effect was maintained for 36 h. Orally administered PLGA NSs modified with chitosan provide an effective means of colon-specific NF-κB decoy delivery in an ulcerative colitis model rat. Pulmonary administration of larger NSs with diameters of several hundred nanometers can be suitable for topical applications, such as the targeted delivery of antiasthmatic drugs into trachea macrophages, while smaller NSs under 100 nm can be used for systemic applications, such as sustained insulin blood levels. PLGA NSs could enhance the skin permeability of drugs depending not only on the size effect but also its material characteristics. Transdermal DDS with PLGA-nanosphere composites has been developed for nanocosmetics, as discussed in Chap. 7.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ishida, T., Kiwada, H.: Accelerated blood clearance of PEGylated liposomes after repeated injection. Drug Deliv. Syst. 19, 495–510 (2004)

    Article  CAS  Google Scholar 

  2. Kataoka, K., Harada, A., Nagasaki, Y.: Block copolymer micel les for drug delivery: design, characterization and biological significance. Adv. Drug Deliv. Rev. 47, 113–131 (2001)

    Article  CAS  Google Scholar 

  3. Igarashi, R., Takenaga, M., Takeuchi, J., Kitagawa, A., Matsumoto, K., Mizushima, Y.: Marked hypotensive and blood flow-increasing effects of a new lipo-PGE1 (lipo-AS013) due to vascular wall targeting. J. Control. Release. 71, 157–164 (2001)

    Article  CAS  Google Scholar 

  4. Toguchi, H., Ogawa, Y., Okada, H., Yamamoto, M.: Once-a-month injectable microcapsules of leuprorelin acetate. Yakugaku Zasshi. 111, 397–409 (1991)

    Article  CAS  Google Scholar 

  5. Okada, H., Doken, Y., Ogawa, Y., Toguchi, H.: Preparation of three-month depot injectable microspheres of leuprorelin acetate using biodegradable polymers. Pharm. Res. 11, 1143–1147 (1994)

    Article  CAS  Google Scholar 

  6. Tahara, K., Yamamoto, H., Kawashima, Y.: Cellular uptake mechanisms and intracellular distributions of polysorbate 80-modified poly(D,L-lactide-co-glycolide) nanospheres for gene delivery. Eur. J. Pharm. Biopharm. 75(2), 218–224 (2010)

    Article  CAS  Google Scholar 

  7. Fessi, H., Puisieux, F., Devissaguet, J.P., Ammoury, N., Benita, S.: Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int. J. Pharm. 55(1), R1–R4 (1989)

    Article  CAS  Google Scholar 

  8. Bodmeier, R., Cohen, H.: Indomethacin polymeric nanosuspension prepared by microfluidization. J. Control. Release. 12, 223–233 (1990)

    Article  CAS  Google Scholar 

  9. Allémann, E., Gurny, R., Doelker, E.: Preparation of aqueous polymeric nanodispersions by a reversible salting-out process, influence of process parameters on particle size. Int. J. Pharm. 87, 247–253 (1992)

    Article  Google Scholar 

  10. Kawashima, Y., Yamamoto, H., Takeuchi, H., Hino, T., Niwa, T.: Properties of a peptide containing DL-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods. Eur. J. Pharm. Biopharm. 45, 41–48 (1998)

    Article  CAS  Google Scholar 

  11. Murakami, H., Kobayashi, M., Takeuchi, H., Kawashima, Y.: Preparation of PLGA nanoparticles by modified spontaneous emulsification solvent diffusion method. Int. J. Pharm. 187, 143–152 (1999)

    Article  CAS  Google Scholar 

  12. Murakami, H., Kobayashi, M., Takeuchi, H., Kawashima, Y.: Further application of a modified spontaneous emulsification solvent diffusion method to various types of PLGA and PLA polymers for preparation of nanoparticles. Powder Technol. 107, 137–143 (2000)

    Article  CAS  Google Scholar 

  13. Kawashima, Y.: Design of Poly(lactic-co-glycolic acid) (PLGA) nanosphere for developing to DDS. J. Pharm. Sci. Technol. Jpn. 66, 224–238 (2006)

    CAS  Google Scholar 

  14. Tahara, K., Sakai, T., Yamamoto, H., Takeuchi, H., Kawashima, Y.: Establishing chitosan coated PLGA nanosphere platform loaded with wide variety of nucleic acid by complexation with cationic compound for gene delivery. Int. J. Pharm. 354(1), 210–216 (2008)

    Article  CAS  Google Scholar 

  15. Tahara, K., Sakai, T., Yamamoto, H., Takeuchi, H., Hirashima, N., Kawashima, Y.: Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells. Int. J. Pharm. 382(1), 198–204 (2009)

    Article  CAS  Google Scholar 

  16. Tsujimoto, H., Tsukada, Y., Hara, K., Kawashima, Y.: New particle design and its preparation of NFkB decoy oligodeoxynucleotide (NDON) loaded PLGA nanospheres for gene delivery. J. Soc. Powder Technol. Jpn. 44, 453–458 (2007)

    Article  CAS  Google Scholar 

  17. Tsukada, Y., Hara, K., Bando, Y., Huang, C.C., Kousaka, Y., Kawashima, Y., Tsujimoto, H.: Particle size control of poly (D,L-lactide-co-glycolide) nanospheres for sterile applications. Int. J. Pharm. 370(1), 196–201 (2009)

    Article  CAS  Google Scholar 

  18. Yamamoto, H., Kurashima, H., Katagiri, D., Yang, M., Takeuchi, H., Kawashima, Y., Yokoyama, T., Tsujimoto, H.: Poly (lactic-co-glycolic acid) nanosphere composite prepared with mechanofusion® dry powder composition system for improving pulmonary insulin delivery with dry powder inhalation. J. Pharm. Sci. Technol. Jpn. 64(4), 245–253 (2004)

    CAS  Google Scholar 

  19. Yamamoto, H., Hoshina, W., Kurashima, H., Takeuchi, H., Kawashima, Y., Yokoyama, T., Tsujimoto, H.: Engineering of poly(D,L -lactic- co -glycolic acid) nanocomposite particles for dry powder inhalation dosage forms of insulin with the spray-fluidized bed granulating system. J. Soc. Powder Technol. Jpn. 41, 514–521 (2004)

    Article  CAS  Google Scholar 

  20. Tsujimoto, H., Hara, K., Kawashima, Y.: Evaluation of glycaemia control in beagle dogs by the administration of insulin encapsulated PLGA nano-composite preparations. J. Soc. Powder Technol. Jpn. 42, 765–772 (2005)

    Article  CAS  Google Scholar 

  21. Tsujimoto, H., Hara, K., Tsukada, Y., Kawashima, Y., Hatano, S.: Use of spouted bed type binderless granulation to design PLGA nano-composite granules for dry powder inhalation. J. Soc. Powder Technol. Jpn. 44, 459–464 (2007)

    Article  CAS  Google Scholar 

  22. Schade, A., Niwa, T., Takeuchi, H., Hino, T., Kawashima, Y.: Aqueous colloidal polymer dispersions of biodegradable DL-lactide/glycolide copolymer as basis for latex films: a new approach for the development of biodegradable depot. Int. J. Pharm. 117, 299–217 (1995)

    Article  Google Scholar 

  23. David Woolfson, A., Karl Malcolm, R., McCarron, P.A., Jones, D.S.: Chapter 41 Bioadhesive drug delivery systems. In: Dumitriu, S. (ed.) Polymeric Biomaterials Revised and Expanded. Taylor and Frances, Washington DC (2001)

    Google Scholar 

  24. Carino, G.P., Jacob, J.S., Mathiowitz, E.: Nanosphere based oral insulin delivery. J. Control. Release. 65, 261–269 (2000)

    Article  CAS  Google Scholar 

  25. Kawashima, Y., Yamamoto, H., Takeuchi, H., Kuno, Y.: Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm. Dev. Technol. 5(1), 77–85 (2000)

    Article  CAS  Google Scholar 

  26. Lamprecht, A., Ubrich, N., Yamamoto, H., Schäfer, U., Takeuchi, H., Maincent, P., Kawashima, Y., Lehr, C.: Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease. J. Pharmacol. Exp. Ther. 299, 775–781 (2001)

    CAS  PubMed  Google Scholar 

  27. Morishita, R., Sugimoto, T., Aoki, M., Kida, I., Tomita, N., Moriguchi, A., Ogihara, T.: In vivo transfection of cis element “decoy” against nuclear factor-κB binding site prevents myocardial infarction. Nat. Med. 3(8), 894–899 (1997)

    Article  CAS  Google Scholar 

  28. Sawa, Y., Morishita, R., Suzuki, K., Kagisaki, K., Kaneda, Y., Maeda, K., Matsuda, H.: A novel strategy for myocardial protection using in vivo transfection of cis element ‘decoy’ against NFkappaB binding site: evidence for a role of NFkappaB in ischemia-reperfusion injury. Circulation. 96(9 Suppl), II–280 (1997)

    CAS  PubMed  Google Scholar 

  29. Tsujimoto, H., Tsukada, Y., Hara, K., Kawashima, Y., Tsujimoto, H., Tsukada, Y., Hara, K., Kawashima, Y.: New particle design and its preparation of NFkB decoy oligodeoxynucleotide (NDON) loaded PLGA nanospheres for gene delivery. J. Soc. Powder Technol. Jpn. 44, 453–458 (2007)

    Article  CAS  Google Scholar 

  30. Tsukada, Y., Tsujimoto, H., Hara, K., Sakaguchi, M., Aoki, M., Morishita, R., Kawashima, Y.: The developments of NFκB Decoy Oligodeoxynucleotides loaded PLGA nanosphere and the applications for atopic dermatitis. In: 2nd International Technical Forum Inspiring Powder Technology, 45-46, November 9, Japan (2006)

    Google Scholar 

  31. Tsukada, Y., Tsujimoto, H., Watanabe, H., Sugimoto, T., Nakano, O., Makino, H., Yamamoto, H., Morishita, R.: Development of oral formulation technology for nucleic acid drug by using PLGA nanoparticles as DDS carriers. J. Soc. Powder Technol. Jpn. 50, 513–518 (2013)

    Article  CAS  Google Scholar 

  32. Yamamoto, H., Kurashima, H., Katagiri, D., Yang, M., Takeuchi, H., Kawashima, Y., Yokoyama, T., Tsujimoto, H.: Poly (lactic-co-glycolic acid) nanosphere composite prepared with mechanofusion® dry powder composition system for improving pulmonary insulin delivery with dry powder inhalation. J. Pharm. Sci. Technol. Jpn. 64(4), 245–253 (2004)

    CAS  Google Scholar 

  33. Yamamoto, H., Hoshina, W., Kurashima, H., Takeuchi, H., Kawashima, Y., Yokoyama, T., Tsujimoto, H.: Engineering of poly(D,L -lactic- co -glycolic acid) nanocomposite particles for dry powder inhalation dosage forms of insulin with the spray-fluidized bed granulating system. J. Soc. Powder Technol. Jpn. 41, 514–521 (2004)

    Article  CAS  Google Scholar 

  34. Tsujimoto, H., Hara, K., Kawashima, Y.: Evaluation of glycaemia control in beagle dogs by the administration of insulin encapsulated PLGA nano-composite preparations. J. Soc. Powder Technol. Jpn. 42, 765–772 (2005)

    Article  CAS  Google Scholar 

  35. Tsujimoto, H., Hara, K., Tsukada, Y., Kawashima, Y., Hatano, S.: Use of spouted bed type binderless granulation to design PLGA nano-composite granules for dry powder inhalation. J. Soc. Powder Technol. Jpn. 44, 459–464 (2007)

    Article  CAS  Google Scholar 

  36. Hara, K., Tsujimoto, H., Huang, C.C., Kawashima, Y., Tsutsumi, M.: Histological examination of PLGA nanospheres for intratracheal drug administration. Int. J. Pharm. 356(1–2), 267–273 (2008)

    Article  CAS  Google Scholar 

  37. Hara, K., Tsujimoto, H., Huang, C.C., Kawashima, Y., Ando, R., Kusuoka, O., Tamura, K., Tsutsumi, M.: Ultrastructural and immunohistochemical studies on uptake and distribution of FITC-conjugated PLGA nanoparticles administered intratracheally in rats. J. Toxicol. Pathol. 25, 19–26 (2012)

    Article  CAS  Google Scholar 

  38. Shim, J.: Transdermal applications of nanoparticulates. Drugs Pharm. Sci. 166, 327 (2007)

    Article  Google Scholar 

  39. Chen, D.L., Zheng, D., Paller, A.S.: Nano-based gene therapy for dermatologic diseases. In: Nanotechnology in Dermatology, pp. 109–117. Springer, New York (2013)

    Chapter  Google Scholar 

  40. Da Silva, C.L., Del Ciampo, J.O., Rossetti, F.C., Bentley, M.V., Pierre, M.B.: Improved in vitro and in vivo cutaneous delivery of protoporphyrin IX from PLGA-based nanoparticles. Photochem. Photobiol. 89(5), 1176–1184 (2013)

    Article  Google Scholar 

  41. Tsujimoto, H., Hara, K., Huang, C.C., Yokoyama, T., Yamamoto, H., Takeuchi, H., Kawashima, Y., Akagi, K., Miwa, N.: Percutaneous absorption study of biodegradable PLGA nano-spheres via human skin biopsies. J. Soc. Powder Technol. Jpn. 41, 867–875 (2004)

    Article  CAS  Google Scholar 

  42. Tsukada, Y., Sasai, A., Tsujimoto, H., Yamamoto, H., Kawashima, Y., Miwa, N.: Practical use of PLGA nanospheres used as DDS carriers for cosmetics. Cosmet. Stage. 7(4), 42–51 (2013)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Engineering, Faculty of Pharmacy, Aichi Gakuin University, Nagoya, Japan

    Yoshiaki Kawashima

Authors
  1. Yoshiaki Kawashima
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kawashima, Y. (2019). Development of a PLGA-Nanosphere DDS Prepared by Spherical Crystallization with a Polymer. In: Spherical Crystallization as a New Platform for Particle Design Engineering. Springer, Singapore. https://doi.org/10.1007/978-981-13-6786-1_6

Download citation

Publish with us

Policies and ethics

Search

Navigation