Enhanced and Extended Anti-Hypertensive Effect of VP5 Nanoparticles

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Abstract

Hypertension has become a significant global public health concern and is also one of the most common risk factors of cardiovascular disease. Recent studies have shown the promising result of peptides inhibiting angiotensin converting enzyme (ACE) in lowering the blood pressure in both animal models and humans. However, the oral bioavailability and continuous antihypertensive effectiveness require further optimization. Novel nanoparticle-based drug delivery systems are helpful to overcome these barriers. Therefore, a poly-(lactic- co-glycolic) acid nanoparticle (PLGANPs) oral delivery system, of the antihypertensive small peptides Val-Leu-Pro-Val-Pro (VLPVP, VP5) model, was developed in this study and its antihypertensive effect was investigated in spontaneously hypertensive rats (SHRs) for the first time. The obtained VP5 nanoparticles (VP5-NPs) showed a small particle size of 223.7 ± 2.3 nm and high entrapment efficiency (EE%) of 87.37% ± 0.92%. Transmission electronic microscopy (TEM) analysis showed that the nanoparticles were spherical and homogeneous. The optimal preparation of VP5-NPs exhibited sustained release of VP5 in vitro and a 96 h long-term antihypertensive effect with enhanced efficacy in vivo. This study illustrated that PLGANPs might be an optimal formulation for oral delivery of antihypertensive small peptides and VP5-NPs might be worthy of further development and use as a potential therapeutic strategy for hypertension in the future.

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Approaches for enhancing oral bioavailability of peptides and proteins.

Jwala Renukuntla, Aswani Dutt Vadlapudi, Ashaben Patel … (2013)

Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1-2%). An ideal oral drug delivery system should be capable of (a) maintaining the integrity of protein molecules until it reaches the site of absorption, (b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and (c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

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A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS.

L Mu, S Feng (2003)

Paclitaxel (Taxol) is one of the best antineoplastic drugs found from nature in the past decades. Like many other anticancer drugs, there are difficulties in its clinical administration due to its poor solubility. Therefore an adjuvant called Cremophor EL has to be employed, but this has been found to cause serious side-effects. However, nanoparticles of biodegradable polymers can provide an ideal solution to the adjuvant problem and realise a controlled and targeted delivery of the drug with better efficacy and fewer side-effects. The present research proposes a novel formulation for fabrication of nanoparticles of biodegradable polymers containing d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) to replace the current method of clinical administration and, with further modification, to provide an innovative solution for oral chemotherapy. In the modified solvent extraction/evaporation technique employed in this research, the emulsifier/stabiliser/additive and the matrix material can play a key role in determining the morphological, physicochemical and pharmaceutical properties of the produced nanoparticles. We found that vitamin E TPGS could be a novel surfactant as well as a matrix material when blended with other biodegradable polymers. The nanoparticles composed of various formulations and manufactured under various conditions were characterised by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. The drug encapsulation efficiency (EE) and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was concluded that vitamin E TPGS has great advantages for the manufacture of polymeric nanoparticles for controlled release of paclitaxel and other anti-cancer drugs. Nanoparticles of nanometer size with narrow distribution can be obtained. A drug encapsulation efficiency as high as 100% can be achieved and the release kinetics can be controlled.

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Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods.

Sergio Galindo-Rodríguez, Eric Allémann, Hatem Fessi … (2004)

The aim of this work was to relate the physicochemical properties of the aqueous and organic phases used for nanoparticle (NP) preparation to the formation of NP produced by salting-out, emulsification-diffusion, and nanoprecipitation. Methacrylic acid copolymer and poly(vinyl alcohol) (PVAL) were selected as NP polymer and emulsifying agent, respectively. Salting-out and emulsification-diffusion NP batches were prepared modifying the PVAL content in the aqueous phase. For nanoprecipitation, NP were produced with variation of the polymer content and type of solvent in the organic phase. For salting-out and emulsification-diffusion, NP formation was discussed in terms of the emulsification theory. The nanoemulsion obtained during NP preparation was visualized by scanning electron microscopy. Aqueous and organic phases used for NP preparation were characterized by their viscosity and surface tension. NP characteristics such as particle mean size, residual surfactant, suspendability in water after freeze-drying, and morphology were explained in terms of these properties. For nanoprecipitation, NP formation was analyzed considering the diffusion-stranding phenomenon. NP formation by salting-out and emulsification-diffusion was related to PVAL chain interactions at the droplet interface (e.g., reduction in the interfacial tension, mechanical stabilization, and steric stabilization) and in the bulk solution (hydrodynamic stabilization). For nanoprecipitation, chi(solvent-water) and delta(delta solvent-water) of the organic phase solvents were well related to the NP characteristics.

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Author and article information

Contributors

Qinghua Qin: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 25 November 2016

Publication date Collection: December 2016

Volume: 17

Issue: 12

Electronic Location Identifier: 1977

Affiliations

[1 ]School of Applied Chemistry and Biological Technology, Shenzhen Polytechnic, Shenzhen 518055, China; tingyu419@ 123456126.com

[2 ]College of Pharmacy, Southwest University for Nationalities, Chengdu 610041, China; zhaoshn11@ 123456163.com (S.Z.); lilihes@ 123456163.com (L.H.)

[3 ]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China; ziqiangli21@ 123456gmail.com (Z.L.); xb1990625@ 123456126.com (B.X.); fangdailongtwozero@ 123456126.com (D.F.); FazhanWang_16@ 123456163.com (F.W.); zhangzhi02@ 123456gmail.com (Z.Z.)

[4 ]Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Yi_Wang@ 123456dfci.harvard.edu

Author notes

[* ]Correspondence: songxr@ 123456scu.edu.cn (X.S.); jiany@ 123456szpt.edu.cn (J.Y.); Tel.: +86-28-8550-3817 (X.S. & J.Y.)

[†]

These authors contributed equally to this work.

Article

Publisher ID: ijms-17-01977

DOI: 10.3390/ijms17121977

PMC ID: 5187777

PubMed ID: 27898022

SO-VID: 1aba5085-211e-46c4-874e-6dd699d73e73

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

History

Date received : 29 September 2016

Date accepted : 18 November 2016

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Enhanced and Extended Anti-Hypertensive Effect of VP5 Nanoparticles

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Most cited references 49

Approaches for enhancing oral bioavailability of peptides and proteins.

A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS.

Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods.

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Cited by 11

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