title: Osteogenic activity of cyclodextrin-encapsulated doxycycline in a calcium phosphate PCL and PLGA composite.
abstract: Composites of biodegradable polymers and calcium phosphate are bioactive and flexible, and have been proposed for use in tissue engineering and bone regeneration. When associated with the broad-spectrum antibiotic doxycycline (DOX), they could favor antimicrobial action and enhance the action of osteogenic composites. Composites of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and a bioceramic of biphasic calcium phosphate Osteosynt® (BCP) were loaded with DOX encapsulated in β-cyclodextrin (βCD) and were evaluated for effects on osteoblastic cell cultures. The DOX/βCD composite was prepared with a double mixing method. Osteoblast viability was assessed with methyl tetrazolium (MTT) assays after 1day, 7day, and 14days of composite exposure; alkaline phosphatase (AP) activity and collagen production were evaluated after 7days and 14days, and mineral nodule formation after 14days. Composite structures were evaluated by scanning electron microscopy (SEM). Osteoblasts exposed to the composite containing 25μg/mL DOX/βCD had increased cell proliferation (p<0.05) compared to control osteoblast cultures at all experimental time points, reaching a maximum in the second week. AP activity and collagen secretion levels were also elevated in osteoblasts exposed to the DOX/βCD composite (p<0.05 vs. controls) and reached a maximum after 14days. These results were corroborated by Von Kossa test results, which showed strong formation of mineralization nodules during the same time period. SEM of the composite material revealed a surface topography with pore sizes suitable for growing osteoblasts. Together, these results suggest that osteoblasts are viable, proliferative, and osteogenic in the presence of a DOX/βCD-containing BCP ceramic composite.
authors.affiliation: Restorative Dentistry Department, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: V C C
authors.initials: VCC
authors.lastname: Trajano
authors.affiliation: Restorative Dentistry Department, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: K J R
authors.initials: KJR
authors.lastname: Costa
authors.affiliation: Department of Oral Clinical, Surgery and Pathology, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: C R M
authors.initials: CRM
authors.lastname: Lanza
authors.affiliation: Chemistry Department, ICEX, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: R D
authors.initials: RD
authors.lastname: Sinisterra
authors.affiliation: Restorative Dentistry Department, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: mecortes@ufmg.br.
authors.forename: M E
authors.initials: ME
authors.lastname: Cortés
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002478:Cells, Cultured; D003505:Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004318:Doxycycline / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002130:Calcium Phosphates; D003505:Cyclodextrins; D004337:Drug Carriers; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; C020243:calcium phosphate; D004318:Doxycycline
keywords: Calcium phosphate; Composite; Doxycycline; Periodontal therapy; Polymers; β-cyclodextrin