Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers
Bone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that <i>Staphylococcus aureus</i> can penetrate bone tissue through micron-sized...
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MDPI AG
2020-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/9/885 |
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| author | Stijn G. Rotman Thomas F. Moriarty Benjamin Nottelet Dirk W. Grijpma David Eglin Olivier Guillaume |
| author_facet | Stijn G. Rotman Thomas F. Moriarty Benjamin Nottelet Dirk W. Grijpma David Eglin Olivier Guillaume |
| author_sort | Stijn G. Rotman |
| collection | DOAJ |
| description | Bone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that <i>Staphylococcus aureus</i> can penetrate bone tissue through micron-sized canaliculi and evade systemic and currently available local antibiotic treatments. Targeting bacteria within the bone requires highly efficient delivery of antimicrobials to the infected bone tissue. In this work, a biodegradable microsphere carrier loaded with antibiotics and with specific affinity to bone mineral was developed. Two widely used antibiotics, i.e., Gentamicin-dioctyl sulfosuccinate (GM-AOT) and Ciprofloxacin (CF) were embedded in poly(ϵ-caprolactone) (PCL) microspheres fabricated by oil-in-water emulsion techniques with carboxylated poly(vinyl alcohol) (cPVA) as surfactant. The carboxylic acid groups present at the Poly(ϵ-caprolactone)/cPVA (PCL-cPVA) microsphere surface were functionalized with aspartic acid oligomers (ASP) granting bone targeting properties. We report on cPVA synthesis, microsphere formulation, and antibiotic loading of PCL/cPVA-ASP microspheres. Antibiotic loaded PCL/cPVA-ASP microspheres show sustained release of its antibiotic load and can inhibit bacterial growth in vitro for up to 6 days. PCL/cPVA-ASP microspheres show enhanced affinity to mineralized substrates compared to non-functionalized PCL/cPVA microspheres. These findings support further development of these bone targeting antibiotic carriers for potential treatment of persistent bone infections. |
| first_indexed | 2024-03-10T16:15:41Z |
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| id | doaj.art-6cb5fd8208a347b7858ff14250fe7f30 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T16:15:41Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6cb5fd8208a347b7858ff14250fe7f302023-11-20T14:05:24ZengMDPI AGPharmaceutics1999-49232020-09-0112988510.3390/pharmaceutics12090885Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic CarriersStijn G. Rotman0Thomas F. Moriarty1Benjamin Nottelet2Dirk W. Grijpma3David Eglin4Olivier Guillaume5AO Research Institute Davos, 7270 Davos Platz, SwitzerlandAO Research Institute Davos, 7270 Davos Platz, SwitzerlandIBMM, University of Montpellier, CNRS, ENSCM, 34093 Montpellier, FranceDepartment of Biomaterials Science and Technology, Faculty of Science and Technology and Technical Medical Centre, University of Twente, 7522 NB Enschede, The NetherlandsAO Research Institute Davos, 7270 Davos Platz, SwitzerlandInstitute of Materials Science and Technology, TU Wien, 1060 Vienna, AustriaBone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that <i>Staphylococcus aureus</i> can penetrate bone tissue through micron-sized canaliculi and evade systemic and currently available local antibiotic treatments. Targeting bacteria within the bone requires highly efficient delivery of antimicrobials to the infected bone tissue. In this work, a biodegradable microsphere carrier loaded with antibiotics and with specific affinity to bone mineral was developed. Two widely used antibiotics, i.e., Gentamicin-dioctyl sulfosuccinate (GM-AOT) and Ciprofloxacin (CF) were embedded in poly(ϵ-caprolactone) (PCL) microspheres fabricated by oil-in-water emulsion techniques with carboxylated poly(vinyl alcohol) (cPVA) as surfactant. The carboxylic acid groups present at the Poly(ϵ-caprolactone)/cPVA (PCL-cPVA) microsphere surface were functionalized with aspartic acid oligomers (ASP) granting bone targeting properties. We report on cPVA synthesis, microsphere formulation, and antibiotic loading of PCL/cPVA-ASP microspheres. Antibiotic loaded PCL/cPVA-ASP microspheres show sustained release of its antibiotic load and can inhibit bacterial growth in vitro for up to 6 days. PCL/cPVA-ASP microspheres show enhanced affinity to mineralized substrates compared to non-functionalized PCL/cPVA microspheres. These findings support further development of these bone targeting antibiotic carriers for potential treatment of persistent bone infections.https://www.mdpi.com/1999-4923/12/9/885drug deliverypoly(aspartic acid)bone infectionbone targetingbone seeking agents |
| spellingShingle | Stijn G. Rotman Thomas F. Moriarty Benjamin Nottelet Dirk W. Grijpma David Eglin Olivier Guillaume Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers Pharmaceutics drug delivery poly(aspartic acid) bone infection bone targeting bone seeking agents |
| title | Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers |
| title_full | Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers |
| title_fullStr | Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers |
| title_full_unstemmed | Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers |
| title_short | Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers |
| title_sort | poly aspartic acid functionalized poly ϵ caprolactone microspheres with enhanced hydroxyapatite affinity as bone targeting antibiotic carriers |
| topic | drug delivery poly(aspartic acid) bone infection bone targeting bone seeking agents |
| url | https://www.mdpi.com/1999-4923/12/9/885 |
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