title: Saquinavir Loaded Acetalated Dextran Microconfetti - a Long Acting Protease Inhibitor Injectable.
abstract: Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral injectables that deliver drug for months at a time have moved into late phase clinical trials. Unfortunately, these solid phase crystal formulations have inherent drawbacks in potential dose dumping and a greater likelihood for burst release of drug compared to polymeric formulations.
  
  
  
  Using electrospinning, acetalated dextran scaffolds containing the protease inhibitor saquinavir were created. Grinding techniques were then used to process these scaffolds into injectables which are termed saquinavir microconfetti. Microconfetti was analyzed for in vitro and in vivo release kinetics.
  
  
  
  Highly saquinavir loaded acetalated dextran electrospun fibers were able to be formed and processed into saquinavir microconfetti while other polymers such as poly lactic-co-glycolic acid and polycaprolactone were unable to do so. Saquinavir microconfetti release kinetics were able to be tuned via drug loading and polymer degradation rates. In vivo, a single subcutaneous injection of saquinavir microconfetti released drug for greater than a week with large tissue retention.
  
  
  
  Microconfetti is a uniquely tunable long acting injectable that would reduce the formation of adherence related HIV resistance. Our findings suggest that the injectable microconfetti delivery system could be used for long acting controlled release of saquinavir and other hydrophobic small molecule drugs.
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman College of Pharmacy, University of North Carolina, 4211 Marsico Hall, 125 Mason Farm Road, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Collier
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, 43210, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Gallovic
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman College of Pharmacy, University of North Carolina, 4211 Marsico Hall, 125 Mason Farm Road, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bachelder
authors.affiliation: Division of Experimental Therapeutics, Eshelman College of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Sykes
authors.affiliation: Division of Experimental Therapeutics, Eshelman College of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Kashuba
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman College of Pharmacy, University of North Carolina, 4211 Marsico Hall, 125 Mason Farm Road, Chapel Hill, North Carolina, 27599, USA. ainsliek@email.unc.edu.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Ainslie
mesh_terms: D000107:Acetylation; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage* / Q000097:blood; D004337:Drug Carriers / Q000008:administration & dosage* / Q000378:metabolism; D065546:Drug Liberation; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000097:blood; D007279:Injections, Subcutaneous; D051379:Mice; D008813:Mice, Inbred ICR; D019258:Saquinavir / Q000008:administration & dosage* / Q000097:blood; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D004337:Drug Carriers; D017320:HIV Protease Inhibitors; D019258:Saquinavir
keywords: Biodegradable polymers; Drug delivery; Electrospinning; Microconfetti