title: Vaginal suppositories containing Lactobacillus acidophilus: development and characterization.
abstract: OBJECTIVE
  The aim of this study was to develop and characterize suppositories for vaginal delivery of Lactobacillus acidophilus.
  
  
  METHODS
  Formulations were performed in order to select suitable excipients based on suppository formation feasibility and cytotoxicity. Solid body and hollow-type suppositories were prepared by melting and molding using poly(ethylene glycol) (PEG) 400 and 4000 or Witepsol (WIT) H12 as excipients. L. acidophilus was incorporated in the molten mass before molding solid body suppositories or added as suspension into the cavity of hollow-type suppositories and sealed molten excipients. Cytotoxicity of the selected excipients was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and lactate dehydrogenase assays against VK2/E6E7, HEC-1-A and HeLa cells. Suppositories were characterized regarding organoleptic characteristics, mass uniformity, disintegration, breaking strength and L. acidophilus in vitro release.
  
  
  RESULTS
  PEG 400, PEG 4000 and WIT H12 showed the absence of toxicity when tested using three different vaginal cell lines. Obtained vaginal suppositories presented uniform and mild texture, a content of about 1 × 10(8) colony-forming units, completely disintegrated in simulated vaginal environment in less than 60 min and provided sustained in vitro release of L. acidophilus. Release studies further demonstrated that incorporation of freeze-dried bacteria did not result in significant loss of viable bacteria, thus supporting that vaginal suppositories may possess good properties to promote the replacement of the vaginal flora in situations of urinary tract infection.
  
  
  CONCLUSIONS
  Hollow-type suppositories showed to be promising delivery vehicles for vaginal delivery of probiotics.
authors.affiliation: a Department of Chemical Sciences , Faculty of Pharmacy, REQUIMTE .
authors.forename: Francisca
authors.initials: F
authors.lastname: Rodrigues
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Maia
authors.forename: José
authors.initials: J
authors.lastname: das Neves
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Amaral
authors.forename: Maria Beatriz P P
authors.initials: MB
authors.lastname: Oliveira
mesh_terms: D000282:Administration, Intravaginal; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007779:Lactobacillus acidophilus; D011092:Polyethylene Glycols / Q000737:chemistry; D019936:Probiotics / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D013488:Suppositories; D014280:Triglycerides / Q000737:chemistry; D014621:Vagina / Q000378:metabolism*
chemical_list: D005079:Excipients; D013488:Suppositories; D014280:Triglycerides; C009683:witepsol; D011092:Polyethylene Glycols; C000595214:polyethylene glycol 4000; C000595213:polyethylene glycol 400
keywords: Cytotoxicity; HEC-1A cells; HeLa cells; LDH; MTS; VK2/E6E7 cells; in vitro release; probiotics; vaginal drug delivery