Synthesis and characterization of surface‐modified PBLG nanoparticles for bone targeting: In vitro and in vivo evaluations

Özcan, İpek; Bouchemal, Kawthar; Segura‐Sánchez, Freimar; Özer, Özgen; Güneri, Tamer; Ponchel, Gilles

doi:10.1002/jps.22678

Cited by 27 publications

(19 citation statements)

References 38 publications

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“…In order to achieve a deeper insight into the phenomenon of nanoparticle accumulation in or on bones, two methods to determine Ca 2+ binding and a binding assay with hydroxyapatite (HA) were performed with PGAS nanoparticles. The Ca 2+ binding test was carried out according to Ozcan et al and Bravo‐Osuna et al Both methods were based on incubation of nanoparticles with Ca 2+ , followed by centrifugation (MiniSpin, Eppendorf, Hamburg, Germany, and Avanti J‐20XP, Beckmann Coulter, Krefeld, Germany) and complexometric titration of the free Ca 2+ with ethylendiaminetetraacetic acid disodium salt. The first method was performed by back titration against calcein solution as the indicator; the second method used direct titration with Eriochrome Black T solution as the indicator.…”

Section: Methodsmentioning

confidence: 99%

Intended and Unintended Targeting of Polymeric Nanocarriers: The Case of Modified Poly(glycerol adipate) Nanoparticles

Weiss

Lucas

Mueller

et al. 2017

Macromolecular Bioscience

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Biodegradable nanoparticles based on stearic acid-modified poly(glycerol adipate) (PGAS) are promising carriers for drug delivery. In order to investigate the impact of the particle interface characteristics on the biological fate, PGAS nanoparticles are covalently and noncovalently coated with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. HPMA copolymer-modified PGAS nanoparticles have similar particle sizes, but less negative zeta-potentials. Nanoparticles are double labeled with the fluorescent dyes DiR (noncovalently) and DYOMICS-676 (covalently bound to HPMA copolymer), and their biodistribution is investigated noninvasively by multispectral optical imaging. Both covalent and noncovalent coatings cause changes in the pharmacokinetics and biodistribution in healthy and tumor-bearing mice. In addition to the intended tumor accumulation, high signals of both fluorescent dyes are also observed in other organs, including liver, ovaries, adrenal glands, and bone. The unintended accumulation of nanocarriers needs further detailed and systematic investigations, especially with respect to the observed ovarian and adrenal gland accumulation.

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Section: Methodsmentioning

confidence: 99%

Intended and Unintended Targeting of Polymeric Nanocarriers: The Case of Modified Poly(glycerol adipate) Nanoparticles

Weiss

Lucas

Mueller

et al. 2017

Macromolecular Bioscience

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“…2 µCi = DPM/(2.22×10 6 ) where, DPM represented the disintegration per minute that was obtained using the following equation: 2 µCi = DPM/(2.22×10 6 ) where, DPM represented the disintegration per minute that was obtained using the following equation:…”

Section: Synthesismentioning

confidence: 99%

“…The synthesis and the characterization of functional poly(-benzyl-l-glutamate) (PBLG) derivatives bearing linked alendronate molecules to develop nanoparticle formulations for bone targeting was also reported 6 . However, to the best of our knowledge, alendronate molecules mainly in single or in multiple molecules have been linked to linear or branched polymers to obtain water-soluble or nanoparticle devices for bone targeting [5][6][7][8][9] . However, to the best of our knowledge, alendronate molecules mainly in single or in multiple molecules have been linked to linear or branched polymers to obtain water-soluble or nanoparticle devices for bone targeting [5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonate–polyaspartamide conjugates as bone targeted drug delivery systems

et al. 2015

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The poly-hydroxyl-aspartamide was used as backbone to synthesize bisphosphonate derivatives thus achieving macromolecular carriers to be potentially used as targeting agents for bone drug delivery. Molecules bearing bisphosphonate groups, such as aminobisphosphonate (ABP) and neridronate (NRD) have been conjugated to polyaspartamide (α,β-poly(N-2-hydroxyethyl)-DL-aspartamide, PHEA), with or without a spacer (succinic acid or 6-aminocaproic acid) thus obtaining PHEA-succinate-ABP and PHEA-caproylcarbammate-ABP and PHEA-ABP and PHEA-NRD, respectively. Bisphosphonate-polymer conjugates were physico-chemically characterized using size exclusion chromatography and 1 H-NMR; and their in vitro and ex-vivo affinity for bone tissue has been further tested using the hydroxylapatite and rabbit bone binding assays, respectively. In vivo studies were carried out using rats to evaluate the biodistribution features of bisphosphonate-polymer conjugates in comparison with the starting PHEA. In vivo findings evidenced a suitable selectivity of bisphosphonate-polymer conjugates toward the bone tissues also as a function of time.

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“…ALN presence did increase bone targeting dramatically in vivo . By labeling the PBLG-PEG-ALN nanospheres with FITC, Ozcan et al was able to demonstrate preferential accumulation of targeted drug in bone [116]. …”

Section: Polymer Carriersmentioning

confidence: 99%

Targeting polymer therapeutics to bone

Low

Kopeček

2012

Advanced Drug Delivery Reviews

134

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An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems.

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Synthesis and characterization of surface‐modified PBLG nanoparticles for bone targeting: In vitro and in vivo evaluations

Cited by 27 publications

References 38 publications

Intended and Unintended Targeting of Polymeric Nanocarriers: The Case of Modified Poly(glycerol adipate) Nanoparticles

Intended and Unintended Targeting of Polymeric Nanocarriers: The Case of Modified Poly(glycerol adipate) Nanoparticles

Bisphosphonate–polyaspartamide conjugates as bone targeted drug delivery systems

Targeting polymer therapeutics to bone

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