Skip to main content
Log in

Tri-component copolymer rods as an implantable reservoir drug delivery system for constant and controllable drug release rate

  • Original Paper
  • Published:
Journal of Polymer Research Aims and scope Submit manuscript

Abstract

Copolymers of (D,L-lactide-random-ε-caprolactone)-block-poly(ethylene glycol)-block-(D,L-lactide-random-ε-caprolactone) (PLECs) were synthesized with varied D,L-lactide (LA) content and different molecular weights (20 and 50 kDa). Polymer ratios, particularly the content of LA, had significant effect on the release of trypan blue. A lower trypan blue release rate was observed from monolithic rods composed of PLECs with higher CL/LA ratio. High LA content in polymer rod led to increase of the hydrophilicity of the polymer rod and the decrease of CL content resulted in the increase of the hydrophilicity of PLECs and hydrolysis rate. Spin-coating technique was employed to coat PCL-b-PEG-b-PCL membrane on PLEC rod with controlled thickness. Results showed that membrane encased rods can produce different release pattern including delayed release, zero-ordered release and burst release depending on the types of inner rod and membrane. Results for this study indicated that PLEC rods could provide the zero-order release profile of highly water-soluble molecules. Moreover, the longer lag phase was observed at higher thickness. These results suggest that these polymer rods were potential drug delivery systems that can provide controlled drug release profiles.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Gliadel wafers for treatment of brain tumors (1998) Med Lett Drugs Ther 40(1035):92

    Google Scholar 

  2. Qian F, Nasongkla N, Gao J (2002) Membrane-encased polymer millirods for sustained release of 5-fluorouracil. J Biomed Mater Res 61(2):203–211

    Article  CAS  Google Scholar 

  3. Qian F, Szymanski A, Gao J (2001) Fabrication and characterization of controlled release poly(D, L-lactide-co-glycolide) millirods. J Biomed Mater Res 55(4):512–522

    Article  CAS  Google Scholar 

  4. Weinberg BD, Ai H, Blanco E, Anderson JM, Gao J (2007) Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods. J Biomed Mater Res Part A 81A(1):161–170

    Article  CAS  Google Scholar 

  5. Khamlao W, Hongeng S, Sakdapipanich J, Nasongkla N (2012) Preparation of self-solidifying polymeric depots from PLEC-PEG-PLEC triblock copolymers as an injectable drug delivery system. J Polym Res 19(3):1–12

    Article  CAS  Google Scholar 

  6. Manaspon C, Hongeng S, Boongird A, Nasongkla N (2012) Preparation and in vitro characterization of SN-38-Loaded, self-forming polymeric depots as an injectable drug delivery system. J Pharm Sci 101(10):3708–3717

    Article  CAS  Google Scholar 

  7. Boongird A, Nasongkla N, Hongeng S, Sukdawong N, Sa-Nguanruang W, Larbcharoensub N (2011) Biocompatibility study of glycofurol in rat brains. Exp Biol Med (Maywood, NJ) 236(1):77–83

    Article  CAS  Google Scholar 

  8. Baker RW (1987) In: Controlled release of biologically active agents. Wiley, New York

  9. Nasongkla N, Bey E, Ren J, Ai H, Khemtong C, Guthi JS, Chin S-F, Sherry AD, Boothman DA, Gao J (2006) Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett 6(11):2427–2430

    Article  CAS  Google Scholar 

  10. Wang Z, Wang S, Guidoin R, Marois Y, Zhang Z (2006) In vitro homogeneous and heterogeneous degradation of poly(ϵ-caprolactone/polyethylene glycol/L-lactide): the absence of autocatalysis and the role of enzymes. J Biomed Mater Res Part A 79A(1):6–15

    Article  CAS  Google Scholar 

  11. Ge H, Hu Y, Jiang X, Cheng D, Yuan Y, Bi H, Yang C (2002) Preparation, characterization, and drug release behaviors of drug nimodipine-loaded poly(ε-caprolactone)-poly(ethylene oxide)-poly(ε-caprolactone) amphiphilic triblock copolymer micelles. J Pharm Sci 91(6):1463–1473

    Article  CAS  Google Scholar 

  12. Shogren R (1997) Water vapor permeability of biodegradable polymers. J Polym Environ 5(2):91–95

    Article  CAS  Google Scholar 

  13. Pearce EM, Schaefgen JR (1977) Contemporary topics in polymer science, vol 2. Plenum, New York

    Book  Google Scholar 

  14. Meidong L, Jianzhong B, Shenguo W (1999) Synthesis and characterization of polycaprolactone/poly(ethylene oxide)/polylactide tri-component copolymers. J Biomater Sci Polym Ed 10(4):501–512

    Article  Google Scholar 

  15. Nasongkla N, Boongird A, Hongeng S, Manaspon C, Larbcharoensub N (2012) Preparation and biocompatibility study of in situ forming polymer implants in rat brains. J Mater Sci Mater Med 23(2):497–505. doi:10.1007/s10856-011-4520-3

    Article  CAS  Google Scholar 

  16. Hu Y, Jiang X, Ding Y, Zhang L, Yang C, Zhang J, Chen J, Yang Y (2003) Preparation and drug release behaviors of nimodipine-loaded poly(caprolactone)–poly(ethylene oxide)–polylactide amphiphilic copolymer nanoparticles. Biomaterials 24(13):2395–2404

    Article  CAS  Google Scholar 

  17. Huang M-H, Li S, Vert M (2004) Synthesis and degradation of PLA–PCL–PLA triblock copolymer prepared by successive polymerization of ε-caprolactone and dl-lactide. Polymer 45(26):8675–8681. doi:10.1016/j.polymer.2004.10.054

    Article  CAS  Google Scholar 

  18. Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Poloniae Pharm—Drug Res 67(3):217–223

    CAS  Google Scholar 

  19. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 15(1):25–35

    Article  CAS  Google Scholar 

  20. Rich J, Jaakkola T, Tirri T, Närhi T, Yli-Urpo A, Seppälä J (2002) In vitro evaluation of poly(epsilon-caprolactone-co-DL-lactide)/bioactive glass composites. Biomaterials 23(10):2143–2150

    Article  CAS  Google Scholar 

  21. Zhang L, Hu Y, Jiang X, Yang C, Lu W, Yang YH (2004) Camptothecin derivative-loaded poly(caprolactone-co-lactide)-b-PEG-b-poly(caprolactone-co-lactide) nanoparticles and their biodistribution in mice. J Control Release 96(1):135–148

    Article  CAS  Google Scholar 

  22. Zhang Y, Wang C, Yang W, Shi B, Fu S (2005) Tri-component diblock copolymers of poly(ethylene glycol)–poly(ε-caprolactone-co -lactide): synthesis, characterization and loading camptothecin. Colloid Polym Sci 283(11):1246–1252

    Article  CAS  Google Scholar 

  23. Mallapragada SK, Peppas NA, Colombo P (1997) Crystal dissolution-controlled release systems. II. Metronidazole release from semicrystalline poly(vinyl alcohol) systems. J Biomed Mater Res 36(1):125–130

    Article  CAS  Google Scholar 

  24. Miyajima M, Koshika A, Ji O, Ikeda M, Nishimura K (1997) Effect of polymer crystallinity on papaverine release from poly (l-lactic acid) matrix. J Control Release 49(2–3):207–215

    Article  CAS  Google Scholar 

  25. Bramfeldt H, Sarazin P, Vermette P (2007) Characterization, degradation, and mechanical strength of poly(D, L-lactide-co-ϵ-caprolactone)-poly(ethylene glycol)-poly(D, L-lactide-co-ϵ-caprolactone). J Biomed Mater Res Part A 83A(2):503–511

    Article  CAS  Google Scholar 

  26. Li S (1999) Hydrolytic degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids. J Biomed Mater Res 48(3):342–353

    Article  CAS  Google Scholar 

  27. Murakami H, Kobayashi M, Takeuchi H, Kawashima Y (2000) Utilization of poly(dl-lactide-co-glycolide) nanoparticles for preparation of mini-depot tablets by direct compression. J Control Release 67(1):29–36

    Article  CAS  Google Scholar 

  28. Valle L, Camps R, Díaz A, Franco L, Rodríguez-Galán A, Puiggalí J (2011) Electrospinning of polylactide and polycaprolactone mixtures for preparation of materials with tunable drug release properties. J Polym Res 18(6):1903–1917

    Article  CAS  Google Scholar 

  29. Babazadeh M, Edjlali L, Rashidian L (2007) Application of 2-hydroxyethyl methacrylate polymers in controlled release of 5-aminosalicylic acid as a colon-specific drug. J Polym Res 14(3):207–213

    Article  CAS  Google Scholar 

  30. Jonnalagadda S, Robinson DH (2000) A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery. AAPS PharmSciTech 1(4):26–34

    Article  Google Scholar 

  31. Tunón Å, Börjesson E, Frenning G, Alderborn G (2003) Drug release from reservoir pellets compacted with some excipients of different physical properties. Eur J Pharm Sci 20(4–5):469–479

    Article  Google Scholar 

  32. Cai K, Yao K, Lin S, Yang Z, Li X, Xie H, Qing T, Gao L (2002) Poly(D, L-lactic acid) surfaces modified by silk fibroin: effects on the culture of osteoblast in vitro. Biomaterials 23(4):1153–1160

    Article  CAS  Google Scholar 

  33. Tiaw KS, Goh SW, Hong M, Wang Z, Lan B, Teoh SH (2005) Laser surface modification of poly(ε-caprolactone) (PCL) membrane for tissue engineering applications. Biomaterials 26(7):763–769

    Article  CAS  Google Scholar 

  34. Sharp JS, Forrest JA, Jones RAL (2001) Swelling of Poly(dl-lactide) and Polylactide-co-glycolide in humid environments. Macromolecules 34(25):8752–8760

    Article  CAS  Google Scholar 

  35. Bei J, Wang W, Wang Z, Wang S (1996) Surface properties and drug release behavior of polycaprolactone polyether blend and copolymer. Polym Adv Technol 7(2):104–107

    Article  CAS  Google Scholar 

  36. Sutton D, Wang S, Nasongkla N, Gao J, Dormidontova EE (2007) Doxorubicin and β-Lapachone release and interaction with micellar core materials: experiment and modeling. Exp Biol Med 232(8):1090–1099

    Article  CAS  Google Scholar 

  37. Rothen-Weinhold A, Besseghir K, Gurny R (1997) Analysis of the influence of polymer characteristics and core loading on the in vivo release of a somatostatin analogue. Eur J Pharm Sci 5(6):303–313

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Thailand Research Fund (TRF) and Commission of Higher Education (CHE) for Norased Nasongkla. Financial support for Tararat Chanlen from the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Office of the Higher Education Commission, Ministry of Education is gratefully acknowledged. We are thankful to Pat Akarajirathun for technical help.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Norased Nasongkla.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chanlen, T., Hongeng, S. & Nasongkla, N. Tri-component copolymer rods as an implantable reservoir drug delivery system for constant and controllable drug release rate. J Polym Res 19, 36 (2012). https://doi.org/10.1007/s10965-012-0036-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10965-012-0036-x

Keywords

Navigation