title: Radio Frequency-Activated Nanoliposomes for Controlled Combination Drug Delivery.
abstract: This work was conducted in order to design, characterize, and evaluate stable liposomes containing the hydrophobic drug raloxifene HCl (RAL) and hydrophilic doxycycline HCl (DOX), two potentially synergistic agents for treating osteoporosis and other bone lesions, in conjunction with a radio frequency-induced, hydrophobic magnetic nanoparticle-dependent triggering mechanism for drug release. Both drugs were successfully incorporated into liposomes by lipid film hydration, although combination drug loading compromised liposome stability. Liposome stability was improved by reducing the drug load and by including Pluronics® (PL) in the formulations. DOX did not appear to interact with the phospholipid membranes comprising the liposomes, and its release was maximized in the presence of radio frequency (RF) heating. In contrast, differential scanning calorimetry (DSC) and phosphorus-31 nuclear magnetic resonance ((31)P-NMR) analysis revealed that RAL developed strong interactions with the phospholipid membranes, most notably with lipid phosphate head groups, resulting in significant changes in membrane thermodynamics. Likewise, RAL release from liposomes was minimal, even in the presence of RF heating. These studies may offer useful insights into the design and optimization of multidrug containing liposomes. The effects of RAL on liposome characteristics and drug release performance underscore the importance of appropriate physical-chemical analysis in order to identify and characterize drug-lipid interactions that may profoundly affect liposome properties and performance early in the formulation development process.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, 02881, USA.
authors.forename: Swapnil A
authors.initials: SA
authors.lastname: Malekar
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, 02881, USA.
authors.forename: Ashish L
authors.initials: AL
authors.lastname: Sarode
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, 02881, USA.
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Bach
authors.affiliation: Department of Chemical Engineering, College of Engineering, University of Rhode Island, 495M Pharmacy Building, 7 Greenhouse Drive, Kingston, Rhode Island, 02881, USA.
authors.forename: Arijit
authors.initials: A
authors.lastname: Bose
authors.affiliation: Department of Chemical Engineering, College of Engineering, University of Rhode Island, 495M Pharmacy Building, 7 Greenhouse Drive, Kingston, Rhode Island, 02881, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bothun
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, 02881, USA. drworthen@uri.edu.|Department of Chemical Engineering, College of Engineering, University of Rhode Island, 495M Pharmacy Building, 7 Greenhouse Drive, Kingston, Rhode Island, 02881, USA. drworthen@uri.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Worthen
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D008081:Liposomes; D010743:Phospholipids; D020442:Poloxamer; D004317:Doxorubicin
keywords: controlled release; drug combination; liposomes; nanoparticles