title: Preparation and in vitro/in vivo characterization of enteric-coated nanoparticles loaded with the antihypertensive peptide VLPVPR.
abstract: Our previous study revealed that the peptide Val-Leu-Pro-Val-Pro-Arg (VLPVPR), which was prepared using deoxyribonucleic acid recombinant technology, effectively decreased the blood pressure of spontaneous hypertensive rats; however, the effect only lasts 6 hours, likely due to its low absorption in the gastrointestinal tract. To overcome this problem, the purpose of this study was to characterize (methoxy-polyethylene glycol)-b-poly(D,L-lactide-co-glycolide)-b-poly(L-lysine) nanoparticles as in vitro and in vivo carriers for the effective delivery of VLPVPR. In our study, the VLPVPR nanoparticles were prepared using a double emulsion method, coated with Eudragit S100, and freeze-dried to produce enteric-coated nanoparticles. The optimized parameters from the double emulsion method was obtained from orthogonal experiments, including drug loading (DL) and encapsulated ratio (ER) at 6.12% and 86.94%, respectively, and the average particle size was below 100 nm. The release experiment demonstrated that the nanoparticles were sensitive to pH: almost completely released at pH 7.4 after 8 hours, but demonstrated much less release at pH 4.5 or pH 1.0 in the same amount of time. Therefore, the nanoparticles are suitable for enteric release. In vivo compared with the untreated group, the medium and high doses of orally administered VLPVPR nanoparticles reduced blood pressure for more than 30 hours, demonstrating that these nanoparticles have long-lasting and significant antihypertensive effects in spontaneously hypertensive rats.
authors.affiliation: Shenzhen Key Laboratory of Fermentation, Purification and Analysis, Shenzhen Polytechnic, Guangdong, People's Republic of China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Shenzhen Key Laboratory of Fermentation, Purification and Analysis, Shenzhen Polytechnic, Guangdong, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory of Fermentation, Purification and Analysis, Shenzhen Polytechnic, Guangdong, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Fermentation, Purification and Analysis, Shenzhen Polytechnic, Guangdong, People's Republic of China.
authors.forename: Xuwei
authors.initials: X
authors.lastname: Tang
authors.affiliation: Shenzhen Key Laboratory of Fermentation, Purification and Analysis, Shenzhen Polytechnic, Guangdong, People's Republic of China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry*; D001794:Blood Pressure / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D004058:Diffusion; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D051381:Rats; D011918:Rats, Inbred SHR; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage / Q000138:chemical synthesis
chemical_list: D000959:Antihypertensive Agents; D020099:Coated Materials, Biocompatible; D053769:Nanocapsules; D010455:Peptides; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer
keywords: Val-Leu-Pro-Val-Pro-Arg peptide; antihypertensive peptide; enteric-coated; in vivo studies; mPEG-PLGA-PLL; nanoparticle
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