title: In situ polyethylene sebacate particulate carriers as an alternative to Freund's adjuvant for delivery of a contraceptive peptide vaccine--A feasibility study.
abstract: The present study evaluates the feasibility of particulate carriers of a biodegradable polymer polyethylene sebacate (PES) as an alternative to Freund's adjuvant in the design of a peptide vaccine formulation. The vaccine formulation comprised of PES and the antigen KLH conjugated 80kDa HSA peptide-1 dissolved in N-methyl-2-pyrrolidone (NMP)/NMP-water as solvent. The antigen revealed good stability and the formulations were readily syringeable. Intradermal injection of the formulations resulted in the formation of PES particulates in situ at the site of injection. The NMP formulations revealed larger particulates which elicited no immunogenic response when injected in rabbits. On the other hand the NMP-water formulation revealed formation of microparticles which were significantly smaller in size, in combination with a small fraction of nanoparticles. It elicited an antibody titer up to 1:3200 in rabbits following intradermal injection. Western blot confirmed generation of antibodies specific to the peptide. Contraceptive efficacy was confirmed by loss of sperm motility and head-to-head agglutination of sperms in the treatment group. Unlike the severe reactions observed with administration of Freund's adjuvant, only mild hypersensitivity reaction was observed with the PES formulations. The mild reaction coupled with the contraceptive efficacy observed suggested PES particulates as a viable alternative to Freund's adjuvant.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (Elite status), N.P. Marg, Matunga (East), Mumbai 400019, India.
authors.forename: Anisha A
authors.initials: AA
authors.lastname: D'Souza
authors.affiliation: Department of Biochemistry and Virology, National Institute for Research in Reproductive Health (ICMR), J.M. Street, Parel, Mumbai 400012, India.
authors.forename: Smita V
authors.initials: SV
authors.lastname: Yevate
authors.affiliation: Department of Biochemistry and Virology, National Institute for Research in Reproductive Health (ICMR), J.M. Street, Parel, Mumbai 400012, India.
authors.forename: A H
authors.initials: AH
authors.lastname: Bandivdekar
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (Elite status), N.P. Marg, Matunga (East), Mumbai 400019, India. Electronic address: pvdevarajan@gmail.com.
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D011091:Polyesters / Q000008:administration & dosage* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D022642:Vaccines, Contraceptive / Q000008:administration & dosage* / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D022642:Vaccines, Contraceptive; D022223:Vaccines, Subunit; C546772:polyethylene sebacate; D005620:Freund's Adjuvant
keywords: 80kDa HSA peptide-1; Contraceptive peptide vaccine; Freund adjuvant; N-methyl-2-pyrrolidone (PubChem CID: 13387); Nanoparticles and microparticles; Polyethylene sebacate