Poly(D,L-lactide-co-glycolide)/hydroxyapatite core–shell nanosphere. Part 2: Simultaneous release of a drug and a prodrug (clindamycin and clindamycin phosphate)

Vukomanović, Marija; Škapin, Srečo D.; Poljanšek, Ida; Žagar, Ema; Kralj, Bogdan; Ignjatović, Nened; Uskoković, Dragan

doi:10.1016/j.colsurfb.2010.09.012

Cited by 36 publications

(19 citation statements)

References 44 publications

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“…One such concept has been applied in the design of HAp nanoparticles for the local delivery of tigecycline in the treatment of osteomyelitis [10]. Sonochemical homogenous precipitation has been used for the controlled synthesis of multifunctional core-shell nanospheres composed of a bioresorbable polymer and HAp for the controlled delivery of clindamycin [11]. …”

Section: Introductionmentioning

confidence: 99%

Multifunctional hydroxyapatite and poly(d,l-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

Ignjatović

Uskoković

Ajduković

et al. 2013

Materials Science and Engineering: C

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Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(D,L)-lactide-co-glycolide (HAp/D3/PLGA). Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems.

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Section: Introductionmentioning

confidence: 99%

Multifunctional hydroxyapatite and poly(d,l-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

Ignjatović

Uskoković

Ajduković

et al. 2013

Materials Science and Engineering: C

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“…Drug release profiles were presented in earlier reports [17, 18], showing 68 wt% of CL released in a month from PLGA/HAP particles and only 0.5 wt% released in the first 24 h. In contrast, the drug desorption from HAP surface followed burst release profile with about 30 % of the drug being released in the first 24 h. In terms of absolute amounts, the comparative release profiles are displayed in Fig.5, showing a more abrupt release from HAP powders due to desorption effect and a more sustained subsequent release driven mostly by the concentration gradient caused by the daily replacement of the medium. On the contrary, the released amount of CL from PLGA/HAP spheres is relatively small in the first 5 days, but is accompanied by a rather rapid release between days 7 and 10 when the swelling-induced erosion of the polymer becomes significant and the small drug is free to diffuse out through the open pores [19].…”

Section: Resultsmentioning

confidence: 99%

Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(d,l-lactide-co-glycolide) powders for the treatment of osteomyelitis

Uskoković

Hoover

Vukomanović

et al. 2013

Materials Science and Engineering: C

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Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, were included in the analysis: monetite, amorphous calcium phosphate and hydroxyapatite. Spherical morphologies and narrow size distribution of both types of nanopowders were confirmed in transmission and scanning electron microscopic analyses. The antibiotic-containing powders exhibited sustained drug release contingent upon the degradation rate of the carrier. Assessment of the antibacterial performance of the antibiotic-encapsulated powders against Staphylococcus aureus, the most common pathogen isolated from infected bone, yielded satisfactory results both in broths and on blood agar plates for all the analyzed powders. In contrast, no cytotoxic behavior was detected upon the incubation of the antibiotic powders with the osteoblastic MC3T3-E1 cell line for up to three weeks. The cells were shown to engage in a close contact with the antibiotic-containing particles, irrespective of their internal or surface phase composition, polymeric or mineral. At the same time, both types of particles upregulated the expression of osteogenic markers osteocalcin, osteopontin, Runx2 and protocollagen type I, suggesting their ability to promote osteogenesis and enhance remineralization of the infected site in addition to eliminating the bacterial source of infection.

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“…On the other hand, the polymeric matrix has been mainly the base form of this drug, which is an active form of this antibiotic. The presence of clindamycin within the both components of PLGA/HAp particles may likewise influence the kinetics of the release of clindamycin from PLGA/HAp core-shells and will present the subject of a further study (Part 2 of this manuscript) [49].…”

Section: Discussionmentioning

confidence: 98%

Poly(d,l-lactide-co-glycolide)/hydroxyapatite core-shell nanospheres. Part 1: A multifunctional system for controlled drug delivery

Vukomanović

Škapin

Jančar

et al. 2011

Colloids and Surfaces B: Biointerfaces

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Poly(D,L-lactide-co-glycolide)/hydroxyapatite core–shell nanosphere. Part 2: Simultaneous release of a drug and a prodrug (clindamycin and clindamycin phosphate)

Cited by 36 publications

References 44 publications

Multifunctional hydroxyapatite and poly(d,l-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

Multifunctional hydroxyapatite and poly(d,l-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(d,l-lactide-co-glycolide) powders for the treatment of osteomyelitis

Poly(d,l-lactide-co-glycolide)/hydroxyapatite core-shell nanospheres. Part 1: A multifunctional system for controlled drug delivery

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