In vitro characterization of bioresorbable polymers and composites for drug delivery and bone replacement

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Doctoral thesis (article-based)
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Date
2002-09-26
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Language
en
Pages
47, [61]
Series
Acta polytechnica Scandinavica. Ch, Chemical technology series, 289
Abstract
A biodegradable device for controlled release of toremifene citrate was studied based upon ε-caprolactone and DL-lactide copolymers (P(CL/DL-LA)) and silica xerogel. The effect of copolymer composition, molecular weight of a copolymer, and drug loading on the release rate of toremifene citrate were investigated and thus it was possible to adjust the release period from 3 months to 1 year. The applicability of the P(CL/DL-LA) copolymers for matrix type controlled release devices was further studied by characterizing the interactions between copolymers and model compounds, theophylline, propranolol hydrochloride and lidocaine by differential scanning calorimetry (DSC) and molecular modelling. The hydrophilicity of the copolymers as well as the level of average molecular weight was modified using different co-initiators i.e. glycerol and polyethylene glycols. Hydrolytic degradation of the copolymers was recorded and the comparison between degradation and release profiles was obtained. The results clearly demonstrated that the desired release rates of these model compounds could be tailored by varying the compound loading, by modifying the hydrophilicity of the matrix copolymer from matrices with low lactide content and by choosing the appropriate comonomer ratio between ε-caprolactone and DL-lactide. Two different composite materials for bone replacement were studied and their properties evaluated in vitro. The first material combined the P(CL/DL-LA) copolymer with bioactive glass S53P4 and the second was a composite consisting of amorphous lactic acid based poly(ester-urethane) (PEU-BDI) with hydroxyapatite (HA) or biphasic calcium phosphate (BCP). The formation of a biologically active Ca-P layer on the surfaces of the composites in hydrolysis indicates in vitro bioactivity and it was found to be dependent on the weight fraction and granule size range of the bioactive glass used. PEU-BDI and its composites with 20 and 40 vol.% bioceramic filler, were characterized prior to their use as biocompatible and bioabsorbable artificial bone materials. The rigidity of the materials was increased with fillers, due to good compatibility with the matrix. Processing by melt blending and sterilization by gamma-irradiation caused some chemical degradation, i.e. loss of molecular weight, but did not affect dynamic mechanical properties. The storage modulus values of all the composite materials remained within ranges that were mechanically compatible with bone over the whole five weeks of hydrolysis. The correlation of in vitro and in vivo bioactivity of the composites needs to be established, but based on the in vitro evaluation, the glass composites have the potential for a variety of applications as implant materials in orthopaedics and dentistry and the PEU-BDI composites have potential for application as fracture fixation materials.
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Keywords
bioresorbable polymers, ε-caprolactone, lactic acid, lactide, copolymer, poly(ester-urethane), drug release, bioactive composite, hydrolysis
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Parts
  • Ahola, M., Rich, J., Kortesuo, P., Kiesvaara, J., Seppälä, J., and Yli-Urpo, A., In vitro evaluation of biodegradable poly(ε-caprolactone-co-DL-lactide)/silica xerogel composites containing toremifene citrate, Int. J. Pharm. 181 (1999) 181-191.
  • Rich, J., Kortesuo, P., Ahola, M., Yli-Urpo, Kiesvaara, J., and Seppälä, J., Effect of the molecular weight of poly(ε-caprolactone-co-DL-lactide) on toremifene citrate release from copolymer/silica xerogel composites, Int. J. Pharm. 212 (2001) 121-130.
  • Karjalainen, T., Rich, J., and Seppälä, J., Release of model compounds from modified lactone copolymers, J. Appl. Polym. Sci. 81 (2001) 2118-2126.
  • Rich, J., Karjalainen, T., Ahjopalo, L., and Seppälä, J., Model compound release from DL-lactide/ε-caprolactone copolymers and evaluation of specific interactions by molecular modelling, accepted in J. Appl. Polym. Sci. 86 (2002) 1-9.
  • Rich, J., Jaakkola, T., Tirri, T., Närhi, T., Yli-Urpo, A., and Seppälä, J., In vitro evaluation of poly(ε-caprolactone-co-DL-lactide)/bioactive glass composites, Biomaterials 23 (2002) 2143-2150.
  • Rich, J., Tuominen, J., Kylmä, J., Seppälä, J., Nazhat, S., and Tanner, K.E., Lactic acid based PEU/HA and PEU/BCP composites: dynamic mechanical characterization of hydrolysis, J. Biomed. Mat. Res. Appl. Biomater. 63 (2002) 346-353.
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https://urn.fi/urn:nbn:fi:tkk-001884