scholarly journals Preparation of a Nanoscaled Poly(vinyl alcohol)/Hydroxyapatite/DNA Complex Using High Hydrostatic Pressure Technology for In Vitro and In Vivo Gene Delivery

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Tsuyoshi Kimura ◽  
Yoichi Nibe ◽  
Seiichi Funamoto ◽  
Masahiro Okada ◽  
Tsutomu Furuzono ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
High Hydrostatic Pressure ◽  
Vinyl Alcohol ◽  
Transgene Expression ◽  
Transfection Efficiency ◽  
Endosomal Escape ◽  
Poly Vinyl Alcohol ◽  
Dna Nanoparticles ◽  
Novel Method

Our previous research showed that poly(vinyl alcohol) (PVA) nanoparticles incorporating DNA with hydrogen bonds obtained by high hydrostatic pressurization are able to deliver DNA without any significant cytotoxicity. To enhance transfection efficiency of PVA/DNA nanoparticles, we describe a novel method to prepare PVA/DNA nanoparticles encapsulating nanoscaled hydroxyapatites (HAps) prepared by high hydrostatic pressurization (980 MPa), which is designed to facilitate endosomal escape induced by dissolving HAps in an endosome. Scanning electron microscopic observation and dynamic light scattering measurement revealed that HAps were significantly encapsulated in PVA/HAp/DNA nanoparticles. The cytotoxicity, cellular uptake, and transgene expression of PVA/HAp/DNA nanoparticles were investigated using COS-7 cells. It was found that, in contrast to PVA/DNA nanoparticles, their internalization and transgene expression increased without cytotoxicity occurring. Furthermore, a similar level of transgene expression between plasmid DNA and PVA/HAp/DNA nanoparticles was achieved using in vivo hydrodynamic injection. Our results show a novel method of preparing PVA/DNA nanoparticles encapsulating HAp nano-crystals by using high hydrostatic pressure technology and the potential use of HAps as an enhancer of the transfection efficiency of PVA/DNA nanoparticles without significant cytotoxicity.

scholarly journals Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy

2015 ◽  
Vol 112 (28) ◽  
pp. 8720-8725 ◽  
Author(s):  
Panagiotis Mastorakos ◽  
Adriana L. da Silva ◽  
Jane Chisholm ◽  
Eric Song ◽  
Won Kyu Choi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Transgene Expression ◽  
Colloidal Stability ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Intratracheal Administration ◽  
Dna Nanoparticles ◽  
High Level

Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration.

scholarly journals Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats

2021 ◽  
pp. 088532822110461
Author(s):  
Tijana Lužajić Božinovski ◽  
Vera Todorović ◽  
Ivan Milošević ◽  
Bogomir Bolka Prokić ◽  
Vladimir Gajdov ◽  
...  
Keyword(s):  
Vinyl Alcohol ◽  
Giant Cells ◽  
Surface Interactions ◽  
Poly Vinyl Alcohol ◽  
Nanocomposite Hydrogels ◽  
Tissue Sections ◽  
Biological Responses ◽  
Statistical Relevance ◽  
Biomaterial Surface

Biocompatibility of materials is one of the most important conditions for their successful application in tissue regeneration and repair. Cell-surface interactions stimulate adhesion and activation of macrophages whose acquaintance can assist in designing novel biomaterials that promote favorable macrophage–biomaterial surface interactions for clinical application. This study is designed to determine the distribution and number of macrophages as a means of biocompatibility evaluation of two newly synthesized materials [silver/poly(vinyl alcohol) (Ag/PVA) and silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) nanocomposite hydrogels] in vivo, with approval of the Ethics Committee of the Faculty of Veterinary Medicine, University of Belgrade. Macrophages and giant cells were analyzed in tissue sections stained by routine H&E and immunohistochemical methods (CD68+). Statistical relevance was determined in the statistical software package SPSS 20 (IBM corp). The results of the study in terms of the number of giant cells localized around the implant showed that their number was highest on the seventh postoperative day (p.o.d.) in the group implanted with Ag/PVA hydrogels, and on the 30th p.o.d. in the group implanted with Ag/PVA/Gr. Interestingly, the number of macrophages measured in the capsular and pericapsular space was highest in the group implanted with the commercial Suprasorb© material. The increased macrophage number, registered around the Ag/PVA/Gr implant on 60th p.o.d. indicates that the addition of graphene can, in a specific way, modulate different biological responses of tissues in the process of wound healing, regeneration, and integration.

scholarly journals Mixed Amphiphilic Polymeric Nanoparticles of Chitosan, Poly(vinyl alcohol) and Poly(methyl methacrylate) for Intranasal Drug Delivery: A Preliminary In Vivo Study

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4496 ◽  
Author(s):  
Inbar Schlachet ◽  
Hen Moshe Halamish ◽  
Alejandro Sosnik
Keyword(s):  
Methyl Methacrylate ◽  
Vinyl Alcohol ◽  
Sodium Tripolyphosphate ◽  
Brain Regions ◽  
Poly Vinyl Alcohol ◽  
Drug Bioavailability ◽  
Poly Methyl Methacrylate ◽  
Target Organs ◽  
The Brain

Intranasal (i.n.) administration became an alternative strategy to bypass the blood–brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1 h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall, results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions, and thus, they could be beneficial in the treatment of different medical conditions.

NOVEL POLYETHYLENIMINE NANOGELS AS POTENTIAL GENE CARRIERS PRODUCED VIA PHOTOCHEMISTRY IN SURFACTANT-FREE AQUEOUS SOLUTION

2006 ◽  
Vol 05 (06) ◽  
pp. 753-756 ◽  
Author(s):  
DONGMEI XU ◽  
JIAHUI YU ◽  
YONGBIAO LIU ◽  
HANWEN SUN ◽  
JINGYING XU ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Transfection Efficiency ◽  
In Vitro Tests ◽  
Gene Carriers ◽  
Polymeric Particles ◽  
Potential Applications ◽  
Novel Method ◽  
Low Toxicity

Cationic polymer nanogels, positively-charged submicrometer polymeric particles that swell in water, have attracted an increasing research attentions in recent years because of their potential applications as gene carriers. In this paper, we report a novel method to synthesize polyethylenimine (PEI) nanogels with sizes ranging from 80 nm to 200 nm via UV irradiation at room temperature in aqueous solution without adding any kind of surfactants. The morphology of the nanoparticles is determined to be spherical. The nanogels are of high stability, high transfection efficiency, low toxicity and low immunogenicity, as having been confirmed by in vivo tests with mice as an animal model, and by in vitro tests with human lung and liver cancer cells as well.

Surface Modified Poly(vinyl alcohol) Nanofiber for the Artificial Corneal Stroma

2007 ◽  
Vol 342-343 ◽  
pp. 209-212 ◽  
Author(s):  
Hisatoshi Kobayashi
Keyword(s):  
Corneal Epithelium ◽  
Vinyl Alcohol ◽  
Type I Collagen ◽  
Corneal Stroma ◽  
Light Transmittance ◽  
Poly Vinyl Alcohol ◽  
Type I ◽  
Nanofiber Sheets

Previously we have found that the immobilization of Type I collagen on the poly(vinyl alcohol)(PVA) hydrogel disc was effective in supporting adhesion and growth of the corneal epithelium and stromal cell in vitro. But the durability of the produced corneal epithelium layer in vivo has some problem. We hypothesized the cell construction force is much stronger than the force of the cell adhesion on the flat modified PVA surfaces. Therefore the improvement of mechanical anchoring force between the substrate and formed corneal cell layer maybe become one of the solving methods. In this study, we prepared the PVA nanofiber mat by using the electrospinning method and the surface modification of the PVA nanofiber was studied to improve the durability of the corneal epithelium layer. The collagen-immobilized PVA nanofiber sheets could support the adhesion and proliferation of rabbit corneal epithelial cells. And the stratified corneal epithelium structure was observed on the PVA nanofiber sheets when the epithelium was co-cultured with rabbit corneal stromal cells. It means that the corneal epithelium was well differentiated on the collagen immobilized PVA nanofiber sheet. The stability of the corneal epithelium layer on the PVA was dramatically improved; the stratified epithelium layer was kept for two weeks after the differentiation introduction, totally after one month. A light transmittance of these materials is not yet enough. Further study to improve the transmission of light, is required.

Poly(vinyl alcohol) Cross-Linkers for in Vivo Injectable Hydrogels

2008 ◽  
Vol 41 (11) ◽  
pp. 3971-3982 ◽  
Author(s):  
Dmitri A. Ossipov ◽  
Sonya Piskounova ◽  
Jöns Hilborn
Keyword(s):  
Vinyl Alcohol ◽  
Poly Vinyl Alcohol ◽  
Injectable Hydrogels

scholarly journals Evaluation of Soft Tissue Regenerative Processes After Subcutaneous Implantation of Silver/ Poly(Vinyl Alcohol) and Novel Silver/Poly(Vinyl Alcohol)/Graphene Hydrogels in an Animal Model

2021 ◽  
Vol 71 (3) ◽  
pp. 285-302
Author(s):  
Tijana Lužajić Božinovski ◽  
Vera Todorović ◽  
Ivan Milošević ◽  
Vladimir Gajdov ◽  
Bogomir Bolka Prokić ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Vinyl Alcohol ◽  
International Standards ◽  
Wound Dressings ◽  
Poly Vinyl Alcohol ◽  
Type Iii Collagen ◽  
Type I ◽  
Subcutaneous Implantation ◽  
Ki 67

Abstract A newly produced biomaterial is necessarily subject of standards, which are performed in vivo on animal models. For the evaluation of soft tissue regenerative possibilities after subcutaneous implantation of biomaterials – silver/poly(vinyl alcohol) (Ag/PVA) and novel silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) provided for clinical use, sixteen rats were used, according to the instructions of international standards, ISO 10993-6, 2007. Histological sections were observed 7, 15, 30 and 60 days after grafting. These hydrogels were produced by in situ electrochemical synthesis of silver nanoparticles in the polymer matrices, which enabled obtaining completely safe and biocompatible materials, free from any additional toxic chemical reducing agents. Surgical implantation of hydrogels was done according to the permission of the Ethical Committee of the Faculty of Veterinary Medicine, University of Belgrade. Immunohistochemical (IHC) studies included the assessment of smooth muscle expression actin in blood vessels (α-SMA), the expression of laminin and type I and type III collagen in the skin structures, and, the determination of cell proliferation marker expression (Ki-67) keratinocytes. The results were assessed in a semiquantitative manner. The data were analyzed in the statistical software package IBM SPSS 20. The conclusions indicated that Ag/PVA/Gr might be used as wound dressings to enhance the tissue healing potential and established faster integration and shorter retention in the tissue.

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