title: Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. II. Antibacterial and osteoblastic response.
abstract: Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release timescales on bacterial and osteoblastic cell cultures. All CAP powders exhibited satisfying antibacterial performance against Staphylococcus aureus, the main causative agent of osteomyelitis. Still, owing to its highest drug adsorption efficiency, the most bacteriostatically effective phase was amorphous CAP with the minimal inhibitory concentration of less than 1 mg/mL. At the same time, the positive cell response and osteogenic effect of the antibiotic-loaded CAP particles was confirmed in vitro for all the sparsely soluble CAP phases. Adsorption of the antibiotic onto CAP particles reversed the deleterious effect that the pure antibiotic exerted on the osteogenic activity of the osteoblastic cells. The simultaneous osteogenic and antimicrobial performance of the material developed in this study, altogether with its ability to exhibit sustained drug release, may favor its consideration as a material base for alternative therapeutic approaches to prolonged antibiotic administration and surgical debridement typically prescribed in the treatment of osteomyelitis.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 94158-2330, USA. vuk21@yahoo.com
authors.forename: Vuk
authors.initials: V
authors.lastname: Uskoković
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002130:Calcium Phosphates / Q000737:chemistry*; D002981:Clindamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010019:Osteomyelitis / Q000188:drug therapy / Q000382:microbiology; D012995:Solubility; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D002981:Clindamycin; C020243:calcium phosphate; C007084:clindamycin phosphate