Effect of membranotropic and mucoadhesive formulations of protein proteinase inhibitors on bovine herpes virus-1 reproduction.
The lipidized derivatives of Bowman-Birk soybean protease inhibitor (BBI) containing one to three oleoyl groups were synthesized and characterized. The (ole)(1)- and (ole)(2)BBI were demonstrated to have 200- and 100-fold higher uptake into Caco-2 cell monolayers compared to native BBI. The acylated BBI had increased affinity to elastase-like proteases. Aprotinin-loaded starch/bovine serum albumin microcapsules were prepared using interfacial cross-linking with terephthaloyl chloride and characterized for their morphology, size and release of the inhibitor. Various formulations of protein proteinase inhibitors were tested for their influence on BHV-1 reproduction in cell cultures. Native aprotinin possessed palpable dose-dependent effect inhibiting the virus reproduction up to 4.0 lg (10,000-fold). The bioadhesive, biodegradable aprotinin-loaded microcapsules were the most effective decreasing virus infectious titer up to 4.0 lg and delaying the cytopathic effect up to 144 h in lesser doses of aprotinin. The lipophilic derivative (ole)(1)BBI was shown to exhibit effective inhibition (>100-fold) of BHV-1 reproduction unlike native BBI.
Larionova
N V
NV
Faculty of Chemistry, The M.V. Lomonosov Moscow State University, 119899, Moscow, Russia. nilar@enzyme.chem.msu.ru
Malykh
E V
EV
Villemson
A L
AL
Krasota
A Ju
AJ
Duchene
D
D
Ollivon
M
M
Gernet
M V
MV
Belousova
R V
RV
Shen
W-C
WC
Larionova
N I
NI
D000268:Adhesiveness; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007611:Aprotinin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D018938:Caco-2 Cells; D002214:Capsules; D002417:Cattle; D002463:Cell Membrane Permeability; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D007242:Herpesvirus 1, Bovine / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D030262:Soybean Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D001672:Biocompatible Materials; D002214:Capsules; D004337:Drug Carriers; D011480:Protease Inhibitors; D030262:Soybean Proteins; D007611:Aprotinin