Microspheres based on poly(3-hydroxy)butyrate for prolonged drug release

Лившиц, В. А.; Бонарцев, А. П.; Иорданский, А. Л.; Иванов, Е. А.; Махина, Т. К.; Мышкина, В. Л.; Бонарцева, Г. А.

doi:10.1134/s1560090409070082

Cited by 19 publications

(14 citation statements)

References 36 publications

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“…5. Degradation of PHB monospheres was seen in the same conditions in analogous experiments, this being apparent as loss of sample weight and changes in shape and integrity [23]. Thus, the overall kinetic profile for drug release from the polymer film consists of the superimposition of two simpler processes: desorption of drug from the polymer matrix by a diffusional mechanism and release in accord with a zeroth-order kinetic equation due to the initial stage of PHB degradation.…”

Section: Resultsmentioning

confidence: 72%

“…At a constant content of low molecular weight substance (rifampicin), the dominant factor affecting the hydrolytic stability of PHB is the hydrophilicity of the system, i.e., the increase in the chitosan concentration. Thus, the physical sense of the linear region of the curve describing constant k, as in previous studies [17,18,22,23], is determined by the pseudo-zeroth order PHB degradation reaction. Two points should be noted in this regard.…”

Section: Resultsmentioning

confidence: 98%

“…It is well known that the more water sorbed in the polymer system, the higher the probability of nucleophilic attack on ester bonds by water molecules. We have previously demonstrated that a number of drug compounds can initiate and accelerate PHB hydrolysis, the extent of this increasing with increases in drug content in the polymer matrix (in films [18] and microspheres [22,23]). At a constant content of low molecular weight substance (rifampicin), the dominant factor affecting the hydrolytic stability of PHB is the hydrophilicity of the system, i.e., the increase in the chitosan concentration.…”

Section: Resultsmentioning

confidence: 98%

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Poly(3-hydroxybutyrate)-chitosan: a new biodegradable composition for prolonged delivery of biologically active substances

et al. 2011

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A new polymer composition based on bacterial poly-3-hydroxybutyrate and chitosan encapsulating the wide-spectrum antibiotic rifampicin was developed. Both biopolymers are biocompatible and can undergo enzymatic and hydrolytic degradation. Variations in the ratio of poly-3-hydroxybutyrate and chitosan in the mixture, altering the ratio of hydrophilic and hydrophobic components, influenced not only the sorption capacities for water and drug but also the controlled release profile of the drug. Analysis of kinetic curves for rifampicin release showed that drug release was determined by the superimposition of two processes: drug desorption by a diffusional mechanism and hydrolytic degradation of poly-3-hydroxybutyrate, which was most marked after the initial diffusional stage. Kinetic parameters (the constant of hydrolysis of poly-3-hydroxybutyrate k and the coefficient of diffusion of rifampicin D) were required for a full description of the poly-3-hydroxybutyrate-chitosan-rifampicin system. The fact that the kinetic curves had a prolonged linear region suggests that this composition may have value as a biodegradable therapeutic system for local controlled drug release.The creation of polymer therapeutic systems for prolonged and targeted delivery of biologically active substances is a relevant but quite difficult practical task. Intense studies of a variety of polymeric drug formulations [1 -5] have led to two principal conclusions: first, that at the micro and submicro levels, the most advantageous biodegradable polymer systems are those whose macromolecules are degraded to nontoxic intermediate and end products [6 -8], and secondly, that the search for polymer carriers often requires the use of mixed compositions with the condition that their physicochemical and delivery properties improve on or modify the properties of the starting polymers [9].With these points in mind, a new polymer system based on bacterial poly-3-hydroxybutyrate (PHB) and chitosan encapsulating the wide-spectrum antibiotic rifampicin (3-[[4-methyl-1-piperazinyl)imino]methyl]rifamycin) was studied. These components for the polymer mixture were selected on the basis that the two polymers are biocompatible [10,11] and can undergo enzymatic and hydrolytic degradation [12,13]. The potential value of PHB-chitosan mixtures arises from the fact that they have an amphiphilic composition and that the hydrophilic:hydrophobic balance of the system can be adjusted. While the polyester PHB is quite hydrophobic and its sorption capacity for water is no greater than 1% (w/w) in normal conditions [14], the equilibrium sorption of water by chitosan, because of its amine and hydroxyl groups, reaches tens of % [15]. Thus, changes in the component ratio allow the water content of the composition to be altered, while the presence of functional groups in chitosan promotes significant increases in the sorption capacity for drugs in the mixture. EXPERIMENTAL SECTIONStudies were performed using bacterial poly(R-3-hydroxybutyrate) as granules obtained from Biomer Co ...

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Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 98%

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Poly(3-hydroxybutyrate)-chitosan: a new biodegradable composition for prolonged delivery of biologically active substances

et al. 2011

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“…The DOX release from microparticles was gradual; during 528 h of the experiment the following content of the drug in the environment was registered: 23.61 ± 1.9, 28.15 ± 1.8, and 34.6 ± 2.3 %, respectively, with the initial load of the microparticles 1, 5, and 10 %. Drug release kinetics from PHA microparticles can be described by diffusion-kinetic equations that were proposed by Livshits and coauthors [19] and Goreva and coauthors [20].…”

Section: Preparation and Investigation Of Dox-loaded Microparticlesmentioning

confidence: 99%

Microparticles prepared from biodegradable polyhydroxyalkanoates as matrix for encapsulation of cytostatic drug

Murueva

Shishatskaya

Kuzmina

et al. 2013

J Mater Sci: Mater Med

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Microparticles made from degradable polyhydroxyalkanoates of different chemical compositions a homopolymer of 3-hydroxybutyric acid, copolymers of 3-hydroxybutyric and 4-hydroxybutyric acids (P3HB/4HB), 3-hydroxybutyric and 3-hydroxyvaleric acids (P3HB/3HV), 3-hydroxybutyric and 3-hydroxyhexanoic acids (P3HB/ 3HHx) were prepared using the solvent evaporation technique, from double emulsions. The study addresses the influence of the chemical compositions on the size and npotential of microparticles. P3HB microparticles loaded with doxorubicin have been prepared and investigated. Their average diameter and n-potential have been found to be dependent upon the level of loading (1, 5, and 10 % of the polymer mass). Investigation of the in vitro drug release behavior showed that the total drug released from the microparticle into the medium increased with mass concentration of the drug. In this study mouse fibroblast NIH 3T3 cells were cultivated on PHA microparticles, and results of using fluorescent DAPI DNA stain, and MTT assay showed that microparticles prepared from PHAs of different chemical compositions did not exhibit cytotoxicity to cells cultured on them and proved to be highly biocompatible. Cell attachment and proliferation on PHA microparticles were similar to those on polystyrene. The cytostatic drug encapsulated in P3HB/3HV microparticles has been proven to be effective against HeLa tumor cells.

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“…, антитромбогенных [15][16][17], антибактериальных [18], противоопухолевых [19][20][21] и других групп [1,2].…”

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Biocompatibility of electrospun poly(3-hydroxybutyrate) and its composites scaffoldsfor tissue engineering

et al. 2014

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Development of biodegradable polymers-based scaffolds for tissue engineering is a promising trend in bioengineering. The electrospun scaffolds from poly(3-hydroxybutyrate) (PHB) were produced using different additives that changed the physical and chemical characteristics of the products. As a result, the construct consisting of interwoven threads of different diameter (0.8-3.4 mm) were obtained, the smallest diameter was observed in the threads from the PHB using tetrabutilammonium iodide (TBAI) and titanium oxide II (TiO2) as additives. Mesenchymal stem cells (MSC) were cultivated on the scaffolds for the biocompatibility evaluation of obtained materials. Cells viability was determined by the XTT assay test. It was shown that the scaffold from the interwoven threads of lowest diameter is most favorable for MSC growth in comparison with the polymer film and scaffolds from the threads of larger diameter. Thus, it was shown that the biocompatibility of electrospun PHB scaffolds depended on their microstructure. The obtained data can be used for development of scaffolds for tissue engineering.

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Microspheres based on poly(3-hydroxy)butyrate for prolonged drug release

Cited by 19 publications

References 36 publications

Poly(3-hydroxybutyrate)-chitosan: a new biodegradable composition for prolonged delivery of biologically active substances

Poly(3-hydroxybutyrate)-chitosan: a new biodegradable composition for prolonged delivery of biologically active substances

Microparticles prepared from biodegradable polyhydroxyalkanoates as matrix for encapsulation of cytostatic drug

Biocompatibility of electrospun poly(3-hydroxybutyrate) and its composites scaffoldsfor tissue engineering

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