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Gentamicin loaded PLGA nanoparticles as local drug delivery system for the osteomyelitis treatment

Posadowska U., Brzychczy-Włoch M., Pamuła E.

Acta of Bioengineering and Biomechanics

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2015

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Vol. 17, no. 3

41--48

EN

Since there are more and more cases of multiresistance among microorganisms, rational use of antibiotics (especially their systemic vs. local application) is of great importance. Here we propose polymeric nanoparticles as locally applied gentamicin delivery system useful in osteomyelitis therapy. Gentamicin sulphate (GS) was encapsulated in the poly(lactide-co-glycolide) (PLGA 85:15) nanoparticles by double emulsification (water/oil/water, W1/O/W2). The nanoparticles were characterized by dynamic light scattering, laser electrophoresis and atomic force microscopy. UV-vis spectroscopy (O-phthaldialdehyde assay, OPA) and Kirby-Bauer tests were used to evaluate drug release and antimicrobial activity, respectively. Physicochemical characterization showed that size, shape and drug solubilization of the nanoparticles mainly depended on GS content and concentration of surface stabilizer (polyvinyl alcohol, PVA). Laser electrophoresis demonstrated negative value of zeta potential of the nanoparticles attributed to PLGA carboxyl end group presence. Drug release studies showed initial burst release followed by prolonged 35-day sustained gentamicin delivery. Agar-diffusion tests performed with pathogens causing osteomyelitis (Staphylococcus aureus and Staphylococcus epidermidis, both reference strains and clinical isolates) showed antibacterial activity of GS loaded nanoparticles (GS-NPs). It can be concluded that GS-NPs are a promising form of biomaterials useful in osteomyelitis therapy.

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Preparation and characterization of drug delivery carriers for local administration of sodium alendronate

Posadowska U., Moreira A., Martins R., Pamuła E.

Engineering of Biomaterials

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2013

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Vol. 16, no. 119

8--12

EN

Osteoporosis is often treated with the use of sodium alendronate - a drug that inhibits osteoclast-mediated bone resorption and regulates rate of bone turnover. However the disadvantage of oral administration of sodium alendronate is poor drug absorption from the gastrointestinal track and severe adverse effects. Therefore we propose local sustained drug delivery systems based on poly(lactide-co-glycolide) (PLGA) micro- and nanocarriers, which can be administered directly by simple injections to the required place in the body. In this study we encapsulated sodium alendronate into PLGA micro- and nanospheres via a double-emulsification technique. Emulsion formation in different shear rate conditions was used to optimize the size of the carriers. The prepared microspheres were observed under an inverted optical microscope which confirmed their micrometric size. The nanospheres were analyzed by atomic force microscopy, which allowed visualization of their shape and measurement of their size. Moreover the hydrodynamic diameter of the nanospheres, polydispersity index as well as zeta potential were examined by dynamic light scattering. The experiments show that drug release does not depend on the size of the carriers. Analyzed carriers do not cause cytotoxicity upon contact with osteoblast like-cells.

3

Shape memory process in resorbable polymers: effect on surface properties and cell adhesion

Costa A. M., Ferreira A. S., Posadowska U., Krok M., Smola A., Dobrzyński P., Pamuła E.

Engineering of Biomaterials

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2012

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Vol. 15, no. 114

8--11

EN

The objectives of this study were to confirm the shape memory behavior of two new bioresorbable terpolymers (L-lactide, glycolide, and trimethylene carbonate: L-PLGTMC and B-PLGTMC), to follow the influence of the shape memory process on their surface properties and to test their cytocompatibility using osteoblast-like cells. For this purpose, foils of both terpolymers were prepared. The terpolymers' ability to recover up to 92-93% of the memorized shape within 10 seconds was obtained. The influence of shape memory process on the surface properties was assessed by water contact angle (WCA) measurement and atomic force microscopy (AFM) and the results suggested that both terpolymers preserved the hydrophilicity after recovery and also that B-PLGTMC polymer was rougher than L-PLGTMC (about 9 folds more). The AFM pictures showed the presence of spherical shape hills on the B-PLGTMC foil surface which after the stretching procedure became oriented toward the direction of the applied load. The terpolymers were seeded on both sides (Top and Bottom faces) with human MG63 osteoblast-like cells. Cell viability was assessed after 1, 3 and 7 days, using MTT assay. Results revealed an increasing number of metabolically active cells with the incubation time, suggesting, together with nitric oxide (NO) level determination, the cytocompatibility of both terpolymers. Cell spreading and morphology were investigated by H&E staining and obtained results corresponded well with ones of MTT and NO.

4

Novel strategies for aminoglycoside antibiotic delivery in skeletal tissues - a review

Posadowska U., Pamuła E.

Engineering of Biomaterials

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2012

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Vol. 15, no. 114

3--7

EN

This paper reviews recent advances concerning antibiotic-loaded microparticles application in osteomyelitis treatment. We discuss different methods utilized for microparticles' preparation, i.e. double emulsification, simple emulsification and spray drying. Materials comprised of sphere-shaped matrices are also presented. We point out that the most commonly used microsphere-building components are biodegrad¬able aliphatic polyesters such as poly(lactide-co-glicolide) PLGA, poly(sebacic-ricinoleic-ester-anhydride) P(SA-RA) and poly(lactic-co-hydroxymethyl glycolic acid) PLHMGA. Biopolymers like gelatin, starch or chitosan are also applied as antibiotic carriers. Relationship between preparation method, type of material and its crosslinking degree, microparticles' immobilization steps and the amount of loaded antibiotic are reported as the main factors controlling release rate of drugs in osteomyelitis treatment. And finally, several approaches to produce injectable formulations as well as implantable three dimensional scaffolds with the use of microparticles are described. All in all, this proves that antibiotic-loaded microspheres are a versatile form of biomaterials in osteomyelitis therapy.