title: The role of hyaluronic acid inclusion on the energetics of encapsulation and release of a protein molecule from chitosan-based nanoparticles.
abstract: The synergistic effects of the polysaccharides chitosan (CS) and hyaluronic acid (HA) formulated into hybrid nanoparticles are promising for drug delivery. In the present work, we performed a detailed analysis of the molecular interactions involved in the TPP-assisted ionotropic gelation of CS hybrid nanoparticles with the objective of investigating the impact of HA inclusion on the particle formulation and on the in vitro release of insulin (INS) as a protein cargo. To do that, an in-depth thermodynamic study was carried out by isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. Such analysis allowed us to elucidate the type and extent of interactions established by INS within the hybrid nanoparticles and to get further knowledge on the nature of its release mechanism in vitro. Overall, INS release from the CS nanoparticles was thermodynamically driven, and when including HA a weaker INS binding to the nanoparticles, hence, a faster release rate in vitro were observed. As a negative polyelectrolyte, HA might have sterically blocked the activated sites of CS, such as the amino groups, through chain entanglement, thereby, attenuating the competitive binding interactions of INS. As a consequence, INS might have experienced a spatial exclusion onto the surface of the hybrid nanoparticles to a greater extent which, in turn, would explain its initial abrupt release.
authors: Nanobiofar Group, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, E-15782 Santiago de Compostela, Spain.
authors: Sonia
authors: S
authors: Al-Qadi
authors: Colloids and Polymers Physics Group, Department of Condensed Matter Physics, Faculty of Physics, University of Santiago de Compostela, Campus Vida, E-15782 Santiago de Compostela, Spain.
authors: Manuel
authors: M
authors: Alatorre-Meda
authors: Unidade de Resonancia Magnética, RIAIDT; University of Santiago de Compostela, Campus Vida, E-15782 Santiago de Compostela, Spain.
authors: Manuel
authors: M
authors: Martin-Pastor
authors: Colloids and Polymers Physics Group, Department of Condensed Matter Physics, Faculty of Physics, University of Santiago de Compostela, Campus Vida, E-15782 Santiago de Compostela, Spain. Electronic address: pablo.taboada@usc.es.
authors: Pablo
authors: P
authors: Taboada
authors: Nanobiofar Group, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, E-15782 Santiago de Compostela, Spain. Electronic address: mdelcarmen.remunan@usc.es.
authors: Carmen
authors: C
authors: Remuñán-López
mesh_terms: D000465:Algorithms; D001667:Binding, Competitive; D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006820:Hyaluronic Acid / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D006820:Hyaluronic Acid; D048271:Chitosan
keywords: Affinity binding; Chitosan nanoparticles; Hyaluronic acid; ITC and NMR; Insulin; ionotropic gelation