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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.

Project description:BackgroundA meta-analysis of eligible studies was performed to evaluate the effectiveness of bone substitute materials (BSMs) in opening wedge high tibial osteotomy (OWHTO) for knee osteoarthritis.MethodsA systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A comprehensive literature search was performed, and studies comparing BSM with bone graft (BG) and without bone graft (WG) were included. The Cochrane risk of bias tool (version 1.0) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool were used to assess the risk of bias for randomized controlled trials (RCTs) and non-randomized studies (NRSs), respectively. The outcomes measured were the osteotomy gap size, the occurrence rates of non-union and lateral hinge fractures, knee functional score, infection and the Visual Analogue Scale (VAS). The quality of evidences was evaluated by Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system.ResultsFive RCTs and eight NRS including 769 participants were included in our meta-analysis. The BSM group had a larger osteotomy gap size than the control group (MD: 0.41 mm, 95% confidence interval (CI): [0.06, 0.76], p=.02, I2=0%), with a significant difference. No significant difference was found between BSM and control group in main analysis in terms of bone non-union, but with a higher non-union rate when BSM combined with long locking plate was used. No significant differences were found in other outcome measures except for VAS from NRS subgroup. The quality of evidence for outcomes was low.ConclusionsBSM combined with locking plate techniques offers a safe and efficient alternative option in OWHTO for osteotomy gap larger than 10 mm, but be aware of the possibility of bone non-union. Given the inherent heterogeneity and low quality of the included studies, future well-designed RCTs are essential to verify the findings.KEY MESSAGEThe treatment of the osteotomy gap is still controversial.BSM combined with a locking plate offers a safe and efficient alternative option for OWHTO with an over 10 mm of osteotomy gap over 10 mm.Due to the inherent heterogeneity and low quality of the included studies, the results should be cautiously interpreted in clinical practice.

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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