Controlled Release of 17β-Estradiol from d,l-Lactide/ε-Caprolactone Copolymers

PurposeEstradiol (E2)-loaded poly(L-lactide-co-glycolide-trimethylenecarbonate) (P(L-LA:GA:TMC)) rods with shape-memory were developed for the treatment of neurodegenerative diseases. Usefulness of the extrusion method in the obtaining process was also considered. The influence of structural and surface properties during hydrolytic degradation was developed. The possible therapeutic aspect of rods with E2 was determined.MethodsThe extruded rods were incubated in a PBS solution (pH 7.4, 37°C, 240 rpm). The amount of released E2 in vitro conditions was estimated by UV-VIS method. The following methods in the degradation of rods were applied: NMR, DSC, FTIR, GPC, SEM, and optical microscopy. Changes in water uptake and weight loss were also determined. In vivo study was performed on rats. Measurements of E2 level were performed before and after ovariectomy of rats using ELISA method. A sample of tissue adjacent to the site of the rod implantation was analysed under an optical microscope.ResultsA stable and steady degradation process ensured zero-order release of E2. The in vivo study indicated a significant increase in the E2 level in serum after ovariectomy. Moreover, structural and surface features indicated that the extrusion method was appropriate for obtaining E2-loaded rods.ConclusionsShape-memory P(L-LA:GA:TMC) rods with E2 are an adequate proposal for further research in the field of neurological disorders.

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“…polylactic acid (12,13), poly(lactide-co-glycolide) (PLGA) (14–16), poly-ε-caprolactone (12), as well as poly-ε-caprolactone/ PLGA blends (8). …”

Section: Introductionmentioning

confidence: 99%

Shape-Memory Terpolymer Rods with 17-β-estradiol for the Treatment of Neurodegenerative Diseases: an In Vitro and In Vivo Study

et al. 2016

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“…[1][2][3][4][5] These polyesters have very different properties. Poly(CL) (PCL) is a semicrystalline polymer (glass transition temperature, T g , = ca.…”

Section: Introductionmentioning

confidence: 99%

Regulation of biodegradability and drug release behavior of aliphatic polyesters by blending

Shen

Sun

Zhu

et al. 2000

J. Biomed. Mater. Res.

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Polyester blending of poly(epsilon-caprolactone) (PCL) with poly(D, L-lactide) (PLA) and their random copolymers (R(CL/LA)) was found to be a convenient approach to regulate the degradation and drug release behaviors of the polyesters. The blend composition and compatibility both affected its degradation and drug release behavior. A DSC study showed that PCL was compatible with 50:50 poly(CL-CO-D,L-LA) (R(50/50)) but incompatible with 25:75 poly(CL-CO-LA) (R(25/75)) and PLA homopolymer. The hydrolysis experiments indicated that with the same CL/LA segment proportion, compatible blends (PCL/R(50/50)) had higher water content and faster weight loss than incompatible blends (PCL/PLA, PCL/R(25/75)). In the compatible blends the PCL degradation rate was increased while that of R(50/50) was decreased. The controlled release kinetics, diffusion constants, and permeation coefficients of the polymer blends were measured by using northindrone (NTD) as a model. The NTD release rates from the polyester blends increased as the CL unit fraction increased but decreased with increasing the LA unit fraction in the blends. With the same CL/LA unit ratios, the NTD release rate from the compatible blend was slower than that from the incompatible blend. The NTD release from the polyester blend was controlled by the diffusion process in the early stage, but the degradation-caused NTD release was later involved. By tailoring the blend composition to such an extent that the degradation-caused release compensated the decline of the diffusion-caused release, a zero-order NTD release was achieved.

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“…29 The obtained materials, which do not contain heavy metals, especially tin, seem to have a promising future as drug carriers introduced intracerebrally.…”

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confidence: 99%

Application of the lithium and magnesium initiators for the synthesis of glycolide, lactide, and ϵ‐caprolactone copolymers biocompatible with brain tissue

Dobrzyński

Kasperczyk

Jelonek

et al. 2006

J Biomedical Materials Res

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The subject of this work is new method of the synthesis of biodegradable copolymers compatible with brain tissue. Copolymerization of glycolide with lactide was conducted in solution or in bulk in the presence of LiBu, LiAcac, MgBu(2), Mg(acac)(2) as initiators. In all cases, copolymers with molecular weight of 20000-40000 were obtained, which enables to use them as drug carriers. During the reactions of copolymer chain growth, the intermolecular transesterification occurs, changing the distribution of comonomeric units in copolymer chain. Magnesium initiators showed a lower contribution to transesterification in comparison with lithium and calcium compounds. The copolymerization of glycolide with epsilon-caprolactone using magnesium compounds as initiators was also described. The random glycolide/epsilon-caprolactone copolymer (10/90) obtained with MgBu(2) was used in in vivo study in the forms of microspheres and foils. Complete degradation of microspheres during 6 weeks was observed after the implantation to brain tissue. All implanted copolymers are compatible with brain tissue.

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Controlled Release of 17β-Estradiol from d,l-Lactide/ε-Caprolactone Copolymers

Cited by 10 publications

References 20 publications

Shape-Memory Terpolymer Rods with 17-β-estradiol for the Treatment of Neurodegenerative Diseases: an In Vitro and In Vivo Study

Shape-Memory Terpolymer Rods with 17-β-estradiol for the Treatment of Neurodegenerative Diseases: an In Vitro and In Vivo Study

Regulation of biodegradability and drug release behavior of aliphatic polyesters by blending

Application of the lithium and magnesium initiators for the synthesis of glycolide, lactide, and ϵ‐caprolactone copolymers biocompatible with brain tissue

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