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Sterilization, storage stability and in vivo biocompatibility of poly(trimethylene carbonate)/poly(adipic anhydride) blends
KTH, Superseded Departments, Polymer Technology.ORCID iD: 0000-0002-1631-1781
KTH, Superseded Departments, Polymer Technology.
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2000 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 21, no 9, 945-955 p.Article in journal (Refereed) Published
Abstract [en]

Biodegradable blends of poly(trimethylene carbonate) (PTMC) and poly(adipic anhydride) (PAA) have been proven to be strong candidates for controlled drug delivery polymers in vitro. We now report on the stability, sterilizability and in vivo local tissue response of these matrices. Blend matrices were sterilized by beta-radiation or ethylene oxide gas treatment, stored at different times and temperatures, and analyzed for changes in physicochemical properties. Moisture uptake at different relative humidities and storage times was determined. Sterilization procedures induced hydrolysis of the matrices. Ethylene oxide gas sterilization had a significantly more marked effect upon the matrix properties than radiation treatment. The onset of degradation was reflected in a decrease of crystallinity and molecular weight along with a change of blend composition. A similar onset of matrix degradation was observed upon storage in air. The physicochemical properties of the blends were well preserved upon storage under argon atmosphere. Biocompatibility of PTMC/PAA implants was assessed in the anterior chamber of rabbits eyes for 1 month. At selected post-operative time points, aqueous humor was analyzed for white blood cells and the corneal thickness was measured. The results suggest good biocompatability of PTMC-rich matrices, whereas fast eroding PAA-rich matrices caused inflammatory responses, due to a burst release of degradation products.

Place, publisher, year, edition, pages
2000. Vol. 21, no 9, 945-955 p.
Keyword [en]
poly(trimethylene carbonate), poly(adipic acid), sterilization, in vivo, degradable blends, implant, DRUG-CARRIER MATRICES, IN-VITRO, BIOERODIBLE POLYANHYDRIDES, CONTROLLED-RELEASE, POLYMERS, DEGRADATION, CARBONATE)
National Category
Polymer Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-13122DOI: 10.1016/S0142-9612(99)00268-9ISI: 000085787000010OAI: oai:DiVA.org:kth-13122DiVA: diva2:321010
Note
QC 20100528Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Design of new biodegradable polymer matrices for controlled drug delivery
Open this publication in new window or tab >>Design of new biodegradable polymer matrices for controlled drug delivery
2000 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

Conventional drug administration technologies display poorcontrollability, and lead to high plasma concentrations andshort duration times, which frequently lead to adverse effects.Controlled release technology aims at predictable andreproducible delivery of an active substance over an extendedperiod of time, yielding optimal response and prolongedefficiency, and thus offering considerable improvement of manytreatments. A powerful approach to controlled drug delivery isthe incorporation of the drug into a biodegradable polymericmatrix, which distributes the active substance in a controlledand sustained fashion as the polymer erodes.

This thesis describes the design of novel biodegradablepolymer matrices for controlled and sustained drug delivery.New functional and biodegradable materials with variableproperties were obtained by homopolymer blending andcopolymerization of building blocks with specific, desirableproperties; poly(adipic anhydride) (PAA), poly(trimethylenecarbonate) (PTMC), poly(1,5-dioxepan-2-one) (PDXO),poly(L-lactide) (PLLA), poly(D,L-lactide) (PDLLA), andpoly(L-lactide-co-1,5-dioxepan-2-one) (P(L-LA-co-DXO).Techniques were developed for the preparation of drug-releasingmatrices in the form of films and microspheres. Variousanalysis techniques, including Differential ScanningCalorimetry,1H-Nuclear Magnetic Resonance, InfraredSpectrometry, Scanning Electron Microscopy, Size ExclusionChromatography and UV-VIS Spectroscopy, were used forcharacterization.

Microspheres encapsulating therapeutic substances wereprepared from P(L-LA-co-DXO) and blends of PDXO with PLLA orPDLLA. The properties, storage stability,degradation and drugrelease characteristics of these matrices were explored,compared and evaluated with special regard to the morphologyand its impact on thein vitrobehavior. Sustained release of drugs wasobtained. The mode of release was strongly influenced by thehydrophilicity of the drug, and by the copolymer/blendcomposition and morphology. The lactide:DXO composition wasproven to be a versatile tool to control the morphology and inturn the rates and pattern of erosion and diffusion ofencapsulated agents from the matrices.

Films were prepared from PTMC-PAA blends, in which PAA actedas a plasticizer. Loss of the fast-degrading PAA componentenhanced the porosity and hydration of the slow-degrading PTMC.A statistical full factorial model was designed to elucidatethe influence of matrix parameters and their interactions. ThePTMC-PAA ratio, the molecular weight of the PTMC, andinteractions amongst these factors significantly influenced therelease performance, mass loss and degree of plasticization andthe relationships obtained enabled the erosion and drug releasepattern to be predicted and controlled. Moisture uptake,storage stability at different relative humidities, and thesterilizability were determined to further explore theversatility of PTMC-PAA matrices. Thein vivolocal tissue response and biocompatibility ofPTMC-PAA implants was assessed in the anterior chamber ofrabbits eyes for 1 month. PTMC-rich matrices displayed goodbiocompatibility.

Key factors that regulate the biological activity of thesepolymeric vehicles were identified as drug solubility,composition, molecular weight, stereochemical configuration,and morphology. By careful design, the degradation and drugrelease characteristics, e.g. kinetics and duration, can bealtered over a broad spectrum. This study shows that structuralchanges of the polymer backbone, and the modeling ofcomposition and morphology provide powerful means of tailoringsystems for specific applications.

Keywords: controlled release, drug delivery, microspheres,polylactide, poly(1,5-dioxepan-2-one), poly(adipic anhydride),poly(trimethylene carbonate), degradation, blends

Place, publisher, year, edition, pages
Stockholm: KTH, 2000. 118 p.
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-2949 (URN)91-7170-534-1 (ISBN)
Public defence
2000-04-14, 00:00 (English)
Note
QC 20100528Available from: 2000-04-18 Created: 2000-04-18 Last updated: 2010-05-28Bibliographically approved

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