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Rola powierzchni i struktury w początkowym uwalnianiu rysperydonu z matryc L-PLGA i D,L-PLGA

Turek A., Kasperczyk J., Jelonek K., Dobrzyński P., Walichiewicz J., Krzemińska K., Smola A., Musiał-Kulik M., Marcinkowski A., Libera M., Gębarowska K., Janeczek H.

Engineering of Biomaterials

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2013

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Vol. 16, no. 118

30--36

PL

W niniejszej pracy była opracowywana implantacyjna postać leku zawierająca rysperydon wytworzona z poli(L-laktydo-ko-glikolidu) (L-PLGA) oraz poli(D,L- laktydo-ko-glikolidu) (D,L-PLGA) zastosowanych jako nośniki leku. Ustalano wpływ właściwości powierzchniowych i strukturalnych na początkowe uwalnianie rysperydonu podczas pierwszych 24 godzin inkubacji. W tym celu zastosowano wysokosprawną chromatografię cieczową, spektroskopię magnetycznego rezonansu jądrowego, skaningową kalorymetrię różnicową, skaningowy mikroskop elektronowy oraz mikroskop sił atomowych. We wszystkich analizowanych danych zaobserwowano różnice pomiędzy matrycami wykonanymi z L-PLGA, a matrycami sporządzonymi z D,L-PLGA. Nie wykazano efektu wyrzutu dla żadnego z badanych polimerów, jakkolwiek ilość uwolnionego leku w przypadku matryc D,L-PLGA była prawie pięciokrotnie wyższa. Kopolimer L-PLGA charakteryzował się znacząco większą średnią długością blokówlaktydylowych iglikolidylowych niż D,L-PLGA. Co więcej, zaobserwowano inny charakter powierzchni analizowanych matryc, to znaczy w przypadku L-PLGA powierzchnia była porowata, podczas gdy w przypadku D,L-laktydu nie obserwowano perforacji. Niewątpliwie istnieje zależność między początkowym uwalnianiem rysperydonu, a topografią i strukturą matryc polimerowych. Przypuszcza się, że większe uwalnianie leku z L-PLGA było bardziej związane z właściwościami powierzchniowymi niż ze strukturą matryc. Otrzymane wyniki wskazują na ogromny potencjał obu tych polimerów i możliwość wybrania optymalnego materiału.

EN

In this work, implantable drug formulation with risperidone on the basis of poly(L-lactide-co-glyco- lide) (L-PLGA) and poly(D,L-lactide-co-glycolide) (D,L-PLGA) as drug carries has been developed. The influence of surface and structural properties on the initial release of risperidone during the first 24 hours has been determined. In this aim, high-performance liquid chromatography, nuclear magnetic resonance spectroscopy, differential scanning calorimetry, scanning electron microscope and atomic force mic¬roscope were used. The differences between L-PLGA and D,L-PLGA matrices in all analyzed data were noted. The burst effect was not revealed for any of the studied polymers, however the released drug was almost five times larger for D,L-PLGA matrices. The L-PLGA copolymer revealed a significantly longer average length of the lactidyl and glycolidyl blocks than D,L-PLGA. Moreover, various characters of surface for analyzed matrices were shown, i.e. in the case of L-PLGA the surface was porous and in the case of D,L-PLGA it was nonporous. Undoubtedly, there were dependences between risperidone's initial release and the topography and the structure of polymeric matrices. We suppose that the larger drug release for L-PLGA was more associated with surface properties than with structure of matrices. The obtained results show the great potential of both polymers and possibility to choose the optimal material.

2

Resorbable scaffolds modified with collagen type I or hydroxyapatite : in vitro studies on human mesenchymal stem cells

Rumian Ł., Wojak I., Scharnweber D., Pamuła E.

Acta of Bioengineering and Biomechanics

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2013

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Vol. 15, no. 1

61--67

EN

Poly(L-lactide-co-glycolide) (PLGA) scaffolds of pore size within the range of 250–320 μm were produced by solvent casting/ porogen leaching method. Afterwards, they were modified through adsorption of collagen type I and incubation in simulated body fluid (SBF) to allow deposition of hydroxyapatite (HAp). The wettability of the scaffolds was measured by sessile drop test. Scanning electron microscopy (SEM) evaluation and energy dispersive X-ray analysis (EDX) were also performed. SEM evaluation and EDX analysis depicted the presence of HAp deposits and a collagen layer on the pore walls on the surface and in the bulk of the scaffolds. Wettability and water droplets penetration time within the scaffolds decreased considerably after applying modifications. Human mesenchymal stem cells (hMSC) were cultured on the scaffolds for 28 days and cell morphology, proliferation and differentiation as well as calcium deposition were evaluated. Lactate dehydrogenase (LDH) activity results revealed that cells cultured on tissue culture polystyrene (TCPS) exhibited high proliferation capacity. Cell growth on the scaffolds was slower in comparison to TCPS and did not depend on modification applied. On the other hand, osteogenic differentiation of hMSC as confirmed by alkaline phosphatase (ALP) activity and mineralization results was enhanced on the scaffolds modified with hydroxyapatite and collagen.

3

Influence of surface and structural properties on the initial release of risperidone from polymeric drug carriers

Turek A., Kasperczyk J., Jelonek K., Dobrzyński P., Walichiewicz J., Krzemińska K., Smola A., Musiał-Kulik M., Marcinkowski A., Libera M., Gębarowska K.

Engineering of Biomaterials

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2012

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Vol. 15, no. 116-117 spec. iss.

144--146

EN

In this work, implantable drug formulation with risperidone on the basis of poly(L-lactide-co-glycolide) (L-PLGA) and poly(D,L-lactide-co-glycolide) (D,L-PLGA) as drug carries was developed. The influence of surface and structural properties on the initial release of risperidone during the first twenty four hours was determined. In this aim, high-performance liquid chromatography, nuclear magnetic resonance spectroscopy, scanning electron microscope and atomic force microscope were used. Significant differences between L-PLGA and D,L-PLGA matrices in all analyzed data were noted. The burst effect was not revealed for any of the studied polymers, however the released drug was almost five times larger for D,L-PLGA matrices. The L-PLGA copolymer revealed a significantly longer average length of the lactidyl and glycolidyl blocks than D,L-PLGA. Moreover, various characters of surface for analyzed matrices were shown, i.e. in case of L-PLGA the surface was porous and in case of D,L-PLGA it was nonporous. Undoubtedly, there were dependences between risperidone's initial release and the topography and the structure of polymeric matrices. We suppose that the larger drug release for L-PLGA was more associated with surface properties and thus structure of matrices. The obtained results showed the great potential of both polymers and possibility to choose the optimal polymer.

4

Surface characterization, collagen adsorption and cell behaviour on poly(L-lactide-co-glycolide)

Adamczak M., Ścisłowska-Czarnecka A., Genet M. J., Dupont-Gillain C. C., Pamula E.

Acta of Bioengineering and Biomechanics

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2011

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Vol. 13, no. 3

63-75

EN

Poly(L-lactide-co-glycolide) (PLG) was modified through the adsorption of collagen to improve the behaviour of fibroblasts and osteoblasts. As reference materials cell-resistant polystyrene (PS) and cell-conductive tissue-culture polystyrene (TCPS) were also evaluated. The physicochemical surface properties of the materials were studied by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and water contact angle measurements. The morphology of cells was examined using optical microscopy, while their growth was evaluated by both crystal violet and MTT tests. Nitric oxide level and protein concentration were tested in cell supernatants. The results showed that the adsorbed amount and the organization of the adsorbed collagen were influenced by surface hydrophobicity. Cell culture experiments on native substrates revealed that cell attachment, spreading and growth enhanced, depending on the substrate, in the following order: PS

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Właściwości powierzchniowe matryc otrzymanych z poli(L-laktydo-ko-glikolidu) z rysperydonem i ich zmiany po dwóch tygodniach degradacji

Turek A., Jelonek K., Wójcik A., Dzierżewicz Z., Kasperczyk J., Dobrzyński P., Marcinkowski A., Trzebicka B.

Engineering of Biomaterials

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2010

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Vol. 13, no. 96-98

117--120

PL

W celu optymalizacji leczenia schizofrenii proponowanych jest wiele rozwiązań. Do jednego z nich należy zastosowanie biodegradowalnych, implantowanych systemów uwalniających leki. W niniejszej pracy badano za pomocą mikroskopii sił atomowych zmiany powierzchni matryc otrzymanych z poli(L-laktydo-koglikolidu) (PLAGA) i rysperydonu przed i po dwóch tygodniach degradacji. Analizowano także wpływ degradacji na zmiany ubytku masy matryc polimerowych. Wyniki wskazują na duże możliwości matryc PLAGA do inkorporowania i pułapkowania rysperydonu. Po dwóch tygodniach stwierdzono stabilność matryc (nie uległy one gwałtownej i niekontrolowanej degradacji). Matryce otrzymane z PLAGA posiadają właściwości powierzchniowe odpowiednie dla zastosowania jako biodegradowalne systemy o kontrolowanym uwalnianiu rysperydonu.

EN

Various solutions are proposed to optimize the therapy of schizophrenia. One of them is the application of biodegradable implantable drug delivery systems. In this work, surface changes of matrices composed of poly(L-lactide-co-glycolide) (PLAGA) and risperidone before and after two weeks of degradation were determined by atomic force microscopy. The influence of degradation on weight loss of matrices was also observed. The results suggest that PLAGA matrices present great potential for incorporation and trapping of risperidone. After two weeks of the studies, the matrices were stable and were not subjected to rapid and uncontrolled degradation. PLAGA matrices have surface properties useful for designing of biodegradable system of controlled risperidone release.

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Coating of poly(l-lactide-co-glycolide) scaffolds with collagen/glycosaminoglycan matrices and their effects on osteoblast behaviour

Wojak I., Pamuła E., Dobrzyński P., Zimmermann H., Worch H., Scharnweber D., Hintze V.

Engineering of Biomaterials

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2009

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Vol. 12, no. 86

9-13

EN

Collagen type I and glycosaminoglycans (GAGs) were immobilized on the surfaces of two types of porous biodegradable poly(L-lactide-co-glycolide) (PLGA) scaffolds with pore size in the range of 250-320 µm and 400-600 µm. Two methods of coating were evaluated differing in the way of how the fibrillogenesis solution was introduced into the pores. The distribution of the immunostained collagen in the volume of the scaffolds was analysed with a laser confocal microscope (LSM). The total amount of collagen and GAGs was measured by Sirius Red and Toluidine Blue assays, respectively. The potential of the scaffolds for cell colonization and differentiation was tested in a dynamic cell culture system using human osteosarcoma cells (SAOS-2). The proliferation of SAOS-2 cells was measured by determining the DNA content on days 2 and 7, while differentiation was analyzed by Calcium- and Phosphate-Assays on days 7 and 14. Differentiation of cells was improved by increasing the pore diameter of the scaffolds, and artificial extracellular matrix (aECM) coatings had an additional positive effect for the scaffolds of both pore sizes.