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Catechol Containing Polyelectrolyte Complex Nanoparticles as Local Drug Delivery System for Bortezomib at Bone Substitute Materials.

ABSTRACT: The proteasome inhibitor bortezomib (BZM) is one of the most potent anti-cancer drugs in the therapy of multiple myeloma. In this study, an adhesive drug delivery system (DDS) for BZM was developed. Therefore, we extended the present DDS concept of polyelectrolyte complex (PEC) nanoparticle (NP) based on electrostatic interactions between charged drug and polyelectrolyte (PEL) to a DDS concept involving covalent bonding between PEL and uncharged drugs. For this purpose, 3,4-dihydroxyphenyl acetic acid (DOPAC) was polymerized via an oxidatively induced coupling reaction. This novel chemo-reactive polyanion PDOPAC is able to temporarily bind boronic acid groups of BZM via its catechol groups, through esterification. PDOPAC was admixed to poly(l-glutamic acid) (PLG) and poly(l-lysine) (PLL) forming a redispersible PEC NP system after centrifugation, which is advantageous for further colloid and BZM loading processing. It was found that the loading capacity (LC) strongly depends on the PDOPAC and catechol content in the PEC NP. Furthermore, the type of loading and the net charge of the PEC NP affect LC and the residual content (RC) after release. Release experiments of PDOPAC/PEC coatings were performed at medically relevant bone substitute materials (calcium phosphate cement and titanium niobium alloy) whereby the DDS worked independently of the surface properties. Additionally, in contrast to electrostatically based drug loading the release behavior of covalently bound, uncharged BZM is independent of the ionic strength (salt content) in the release medium.

SUBMITTER: Vehlow D

PROVIDER: S-EPMC7557399 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Catechol Containing Polyelectrolyte Complex Nanoparticles as Local Drug Delivery System for Bortezomib at Bone Substitute Materials.

Vehlow David D Wong Jeremy P H JPH Urban Birgit B Weißpflog Janek J Gebert Annett A Schumacher Matthias M Gelinsky Michael M Stamm Manfred M Müller Martin M

Pharmaceutics 20200824 9

The proteasome inhibitor bortezomib (BZM) is one of the most potent anti-cancer drugs in the therapy of multiple myeloma. In this study, an adhesive drug delivery system (DDS) for BZM was developed. Therefore, we extended the present DDS concept of polyelectrolyte complex (PEC) nanoparticle (NP) based on electrostatic interactions between charged drug and polyelectrolyte (PEL) to a DDS concept involving covalent bonding between PEL and uncharged drugs. For this purpose, 3,4-dihydroxyphenyl aceti ...[more]

PMID: 32847150

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Project description:ObjectiveTo assess the efficacy of using a bone substitute material (BSM) in the fixture-socket gap in patients undergoing tooth extraction and immediate implant placement.Materials and methodsMEDLINE, EMBASE, and CENTRAL databases were searched for randomized controlled trials (RCTs). RCTs were screened for eligibility, and data were extracted by two authors independently. Risk of bias (ROB) was assessed using Cochrane's ROB tool 2.0. Primary outcomes were implant failure, overall complications, and soft-tissue esthetics. Secondary outcomes were vertical buccal bone resorption, vertical interproximal bone resorption, horizontal buccal bone resorption, and mid-buccal mucosal recession. Meta-analysis was performed using random-effects model with generic inverse variance weighing. GRADE was used to grade the certainty of the evidence.ResultsAfter screening 19 544 potentially eligible references, 20 RCTs were included in this review, with a total of 848 patients (916 sites). Most included RCTs were deemed of some concerns (53%) or at low (38%) risk of bias, except for overall complications (high ROB). Implant failure did not differ significantly RR = 0.92 (confidence intervals [CI] 0.34 to 2.46) between using a BSM compared with not using a BSM (NoBSM). BSM use resulted in less horizontal buccal bone resorption (MD = -0.52 mm [95% CI -0.74 to -0.30]), a higher esthetic score (MD = 1.49 [95% CI 0.46 to 2.53]), but also more complications (RR = 3.50 [95% CI 1.11 to 11.1] compared with NoBSM. Too few trials compared types of BSMs against each other to allow for pooled analyses. The certainty of the evidence was considered moderate for all outcomes except implant failure (low), overall complications (very low), and vertical interproximal bone resorption (very low).ConclusionBSM use during immediate implant placement reduces horizontal buccal bone resorption and improves the periimplant soft-tissue esthetics. Although BSM use increases the risk of predominantly minor complications.

Dataset Information

Catechol Containing Polyelectrolyte Complex Nanoparticles as Local Drug Delivery System for Bortezomib at Bone Substitute Materials.

Publications

Catechol Containing Polyelectrolyte Complex Nanoparticles as Local Drug Delivery System for Bortezomib at Bone Substitute Materials.

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