Injectable PLGA/Hydroxyapatite/Chitosan Microcapsules Produced by Supercritical Emulsion Extraction Technology: An In Vitro Study on Teriparatide/Gentamicin Controlled Release.
Supercritical emulsion extraction (SEE) is proposed as a green and effective strategy for the fabrication of chitosan-covered poly-lactic-co-glycolic acid (chi-PLGA) injectable microcapsules for the controlled release of teriparatide (THA) and teriparatide/gentamicin sulfate (THA/Gen). These formulations can be used for locally bone pathologies treatment or in complex fracture healing of aged patients. Several oil-water (o-w) and water-oil-water (w-o-w) emulsions were processed by SEE to produce multifunctional microcapsules containing hydroxyapatite (HA) within a poly-lactic-co-glycolic acid (PLGA) matrix (up to 24 mg/g) and with both THA (0.45 mg/g) and Gen (up to 9 mg/g). Chitosan coating was also successfully added, as external layer (0.4 μm). SEE-fabricated microcapsules showed good encapsulation efficiency (up to 90%) for all the drugs tested and a mean size ranging between 1.4 (±0.4) μm and 2.2 (±0.5) μm. Different drug amounts loaded and microcapsules compositions assured a controlled drug release over a wide range of times and concentrations, as in vitro monitored in PBS medium at 37°C for 15/20 days. HA embedded into the biopolymer structure delayed the THA release profile; chitosan coating strongly reduced the initial drug "burst" release. In addition, the coencapsulation of both THA and Gen, which have very different water solubility, accelerated the release profile of the less water-soluble drug. No drugs degradation was also monitored after the SEE manufacturing. Apparent drug diffusivities (D) were calculated by fitting of the release profiles. In the case of Gen, D ranged between 2.9 × 10(-8) and 1.6 × 10(-9) cm(2)s(-1) if the drug was entrapped in simple PLGA or in the chitosan-coated microcapsules, respectively. In the case of THA, the calculated values ranged between 8.1 × 10(-9) and 7.4 × 10(-10) cm(2)s(-1) when the drug was entrapped in PLGA/HA microcapsules or in the chitosan-coated ones, respectively. These mass transfer values are consistent with the different release behaviors observed and confirmed the possibility of multicomponent microcapsules fabrication by SEE.
Department of Industrial Engineering, University of Salerno, Fisciano, Salerno 84084, Italy. Electronic address: gdellaporta@unisa.it.
Giovanna
G
Della Porta
Department of Industrial Engineering, University of Salerno, Fisciano, Salerno 84084, Italy.
Roberta
R
Campardelli
Department of Industrial Engineering, University of Salerno, Fisciano, Salerno 84084, Italy.
Vincenzo
V
Cricchio
Department of Orthopedics and Traumatology, University of Rome "Tor Vergata" School of Medicine, Rome, Italy.
Francesco
F
Oliva
Department of Musculoskeletal Medicine and Surgery, Faculty of Medicine and Surgery, University of Salerno, Baronissi, Salerno 84081, Italy.
Nicola
N
Maffulli
Department of Industrial Engineering, University of Salerno, Fisciano, Salerno 84084, Italy.
Ernesto
E
Reverchon
D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000737:chemistry*; D002214:Capsules; D048271:Chitosan / Q000737:chemistry; D025924:Chromatography, Supercritical Fluid; D003692:Delayed-Action Preparations; D017886:Durapatite / Q000737:chemistry; D004655:Emulsions; D005079:Excipients; D005839:Gentamicins / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D019379:Teriparatide / Q000008:administration & dosage / Q000737:chemistry*
D050071:Bone Density Conservation Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D005839:Gentamicins; D011500:Protein Synthesis Inhibitors; D019379:Teriparatide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D017886:Durapatite
PLGA; controlled release; drug delivery systems; microencapsulation; supercritical fluids