title: Spray drying tenofovir loaded mucoadhesive and pH-sensitive microspheres intended for HIV prevention.
abstract: OBJECTIVE
  To develop spray dried mucoadhesive and pH-sensitive microspheres (MS) based on polymethacrylate salt intended for vaginal delivery of tenofovir (a model HIV microbicide) and assess their critical biological responses.
  
  
  METHODS
  The formulation variables and process parameters are screened and optimized using a 2(4-1) fractional factorial design. The MS are characterized for size, zeta potential, yield, encapsulation efficiency, Carr's index, drug loading, in vitro release, cytotoxicity, inflammatory responses and mucoadhesion.
  
  
  RESULTS
  The optimal MS formulation has an average size of 4.73μm, zeta potential of -26.3mV, 68.9% yield, encapsulation efficiency of 88.7%, Carr's index of 28.3 and drug loading of 2% (w/w). The MS formulation release 91.7% of its payload in the presence of simulated human semen. At a concentration of 1mg/ml, the MS are noncytotoxic to vaginal endocervical/epithelial cells and Lactobacillus crispatus when compared to control media. There is also no statistically significant level of inflammatory cytokine (IL1-α, IL-1β, IL-6, IL-8, and IP-10) release triggered by these MS. Their percent mucoadhesion is 2-fold higher than that of 1% HEC gel formulation.
  
  
  CONCLUSIONS
  These data suggest the promise of using such MS as an alternative controlled microbicide delivery template by intravaginal route for HIV prevention.
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Science, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Vivek
authors.initials: V
authors.lastname: Agrahari
authors.forename: James B
authors.initials: JB
authors.lastname: Murowchick
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Oyler
authors.forename: Bi-Botti C
authors.initials: BB
authors.lastname: Youan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D010316:Particle Size; D000068698:Tenofovir
chemical_list: D004337:Drug Carriers; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine