Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Development of Novel EE/Alginate Polyelectrolyte Complex Nanoparticles for Lysozyme Delivery: Physicochemical Properties and In Vitro Safety.

ABSTRACT: The number of biologic drugs has increased in the pharmaceutical industry due to their high therapeutic efficacy and selectivity. As such, safe and biocompatible delivery systems to improve their stability and efficacy are needed. Here, we developed novel cationic polymethacrylate-alginate (EE-alginate) pNPs for the biologic drug model lysozyme (Lys). The impact of variables such as total charge and charge ratios over nanoparticle physicochemical properties as well as their influence over in vitro safety (viability/proliferation and cell morphology) on HeLa cells was investigated. Our results showed that electrostatic interactions between the EE-alginate and lysozyme led to the formation of EE/alginate Lys pNPs with reproducible size, high stability due to their controllable zeta potential, a high association efficiency, and an in vitro sustained Lys release. Selected formulations remained stable for up to one month and Fourier transform-Infrared (FT-IR) showed that the functional groups of different polymers remain identifiable in combined systems, suggesting that Lys secondary structure is retained after pNP synthesis. EE-alginate Lys pNPs at low concentrations are biocompatible, while at high concentrations, they show cytotoxic for HeLa cells, and this effect was found to be dose-dependent. This study highlights the potential of the EE-alginate, a novel polyelectrolyte complex nanoparticle, as an effective and viable nanocarrier for future drug delivery applications.

SUBMITTER: Sepulveda-Rivas S

PROVIDER: S-EPMC6470925 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system.

Project description:In this study, chitosan-alginate polyelectrolyte microparticles containing the antibiotic, vancomycin chloride were prepared using the ionotropic gelation (coacervation) technique. In vitro release and drug transport mechanisms were studied concerning the chitosan only and alginate only microparticles as a control group. Further, the effect of porosity on the drug transport mechanism was also studied for chitosan-alginate mixed particles produced by lyophilizing in contrast to the air-dried non-porous particles. According to the in vitro release data, alginate only and chitosan only microparticles showed burst release and prolonged release respectively. Chitosan-alginate lyophilized microparticles showed the best-controlled release of vancomycin with the average release of 22?g per day for 14days. Also, when increasing alginate concentration there was no increase in the release rate of vancomycin. The release data of all the microparticles were treated with Ritger-Peppas, Higuchi, Peppas-Sahlin, zero-order, and first-order kinetic models. The best fit was observed with Peppas-Sahlin model, indicating the drug transport mechanism was controlled by both Fickian diffusion and case II relaxations. Also, Fickian diffusion dominates the drug transport mechanism of all air-dried samples during the study period. However, the Fickian contribution was gradually reducing with time. Porosity significantly effects the drug transport mechanism as case II relaxation dominates after day 10 of the lyophilized microparticles.

| S-EPMC5805659 | biostudies-literature

Synthesis of β-cyclodextrin-lysozyme conjugates and their physicochemical and biochemical properties.

Project description:Recently a great interest in the field of protein engineering and the design of innovative drug delivery systems employing specific ligands such as cyclodextrins is observed. The paper reports the solid state, thermal method for protein coupling with β-cyclodextrin and the physicochemical and biological properties of the obtained conjugates. The structure of the obtained conjugates was investigated via liquid chromatography-mass spectrometry, dynamic light scattering and circular dichroism analysis. The presented conjugates were biologically active and covalently bound β-cyclodextrin preserved the ability to form inclusion complexes with the model compound. This report demonstrates the great potential of cyclodextrin as a modifying unit that can be used to modulate the properties of therapeutic proteins, additionally giving such conjugates the possibility to transport many therapeutic substances in the form of inclusion complexes. In addition, the paper presents the potential of protein-cyclodextrin conjugates to construct innovative bioactive molecules for biological and medical applications.

| S-EPMC5350216 | biostudies-literature

Effects of Starch Incorporation on the Physicochemical Properties and Release Kinetics of Alginate-Based 3D Hydrogel Patches for Topical Delivery.

Project description:The development of printable hydrogel inks for extrusion-based 3D printing is opening new possibilities to the production of new and/or improved pharmaceutical forms, specifically for topical application. Alginate and starch are natural polysaccharides that have been extensively exploited due to their biocompatibility, biodegradability, viscosity properties, low toxicity, and relatively low cost. This research work aimed to study the physicochemical and release kinetic effects of starch incorporation in alginate-based 3D hydrogel patches for topical delivery using a quality by design approach. The incorporation of a pregelatinized starch is also proposed as a way to improve the properties of the drug delivery system while maintaining the desired quality characteristics. Critical material attributes and process parameters were identified, and the sensitivity and adequacy of each parameter were statistically analyzed. The impact of alginate, starch, and CaCl2·2H2O amounts on relevant quality attributes was estimated crosswise. The amount of starch revealed a synergetic impact on porosity (p = 0.0021). An evident increase in the size and quantity of open pores were detected in the as printed patches as well as after crosslinking (15.6 ± 5.2 µm). In vitro drug release studies from the optimized alginate-starch 3D hydrogel patch, using the probe Rhodamine B, showed an initial high burst release, followed by a controlled release mechanism. The results obtained also showed that the viscoelastic properties, printing accuracy, gelation time, microstructure, and release rates can be modulated by varying the amount of starch added to the system. Furthermore, these results can be considered an excellent baseline for future drug release modulation strategies.

| S-EPMC7466037 | biostudies-literature

Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles.

Project description:We posit that cell-mediated drug delivery can improve transport of therapeutic enzymes to the brain and decrease inflammation and neurodegeneration seen during Parkinson's disease. Our prior works demonstrated that macrophages loaded with nanoformulated catalase ('nanozyme') then parenterally injected protect the nigrostriatum in a murine model of Parkinson's disease. Packaging of catalase into block ionomer complex with a synthetic polyelectrolyte block copolymer precludes enzyme degradation in macrophages.We examined relationships between the composition and structure of block ionomer complexes with a range of block copolymers, their physicochemical characteristics, and loading, release and catalase enzymatic activity in bone marrow-derived macrophages.Formation of block ionomer complexes resulted in improved aggregation stability. Block ionomer complexes with ?-polylysine and poly(L-glutamic acid)-poly(ethylene glycol) demonstrated the least cytotoxicity and high loading and release rates. However, these formulations did not efficiently protect catalase inside macrophages.Nanozymes with polyethyleneimine- and poly(L-lysine)(10)-poly(ethylene glycol) provided the best protection of enzymatic activity for cell-mediated drug delivery.

| S-EPMC3037278 | biostudies-literature

Unexpected Plasticization Effects on the Structure and Properties of Polyelectrolyte Complexed Chitosan/Alginate Materials.

Project description:This work describes the effects of different plasticizers, namely, glycerol, triacetin, and 1-ethyl-3-methylimidazolium acetate ([C2 mim][OAc]), on the structure and properties of thermomechanically processed, bulk chitosan and chitosan/alginate materials. Mechanical data shows that, for the chitosan matrix, glycerol and [C2 mim][OAc] were highly effective at reducing intra- and intermolecular forces between biopolymer chains, leading to increased ductility, while the plasticization effect of triacetin was minor. Nonetheless, this triester effectively suppressed biopolymer recrystallization, whereas [C2 mim][OAc] promoted it. In contrast, for the chitosan/alginate matrix, inclusion of triacetin resulted in increased recrystallization, higher thermal stability, and excellent mechanical properties. The triacetin assisted the interactions between biopolymer chains in this polyelectrolyte complexed system. In contrast, the chitosan/alginate material plasticized by [C2 mim][OAc] displayed the most apparent phase separation, poorest mechanical properties, and highest surface hydrophilicity, behavior associated with the disruption of polyelectrolyte complexation and hydrogen bonding between biopolymer chains. Interestingly, the formation of a "new structure" under the electron beam during microscopy imaging was observed, likely from coordination between alginate and [C2 mim][OAc]. Thus, this work has revealed the strong and unexpected effects of three different plasticizers on the hydrogen bonding and electrostatic interactions within chitosan/alginate polyelectrolyte complexed materials, which have potential for biomedical applications where balanced hydrophilicity and mechanical properties are required.

| S-EPMC7886053 | biostudies-literature

Shielding of Lipid Nanoparticles for siRNA Delivery: Impact on Physicochemical Properties, Cytokine Induction, and Efficacy.

Project description:Formulation of short interfering RNA (siRNA) into multicomponent lipid nanoparticles (LNP) is an effective strategy for hepatic delivery and therapeutic gene silencing. This study systematically evaluated the effect of polyethylene glycol (PEG) density on LNP physicochemical properties, innate immune response stimulation, and in vivo efficacy. Increased PEG density not only shielded LNP surface charge but also reduced hemolytic activity, suggesting the formation of a steric barrier. In addition, increasing the PEG density reduced LNP immunostimulatory potential as reflected in cytokine induction both in vivo and in vitro. Higher PEG density also hindered in vivo efficacy, presumably due to reduced association with apolipoprotein E (ApoE), a protein which serves as an endogenous targeting ligand to hepatocytes. This effect could be overcome by incorporating an exogenous targeting ligand into the highly shielded LNPs, thereby circumventing the requirement for ApoE association. Therefore, these studies provide useful information for the rational design of LNP-based siRNA delivery systems with an optimal safety and efficacy profile.

| S-EPMC4459547 | biostudies-other

Relationship Between the Physicochemical Properties of Lipid Nanoparticles and the Quality of siRNA Delivery to Liver Cells.

Project description:While a variety of short interfering RNA (siRNA) delivery compounds have been developed, a deep understanding of the key parameters that determine the quality of siRNA delivery are not known with certainty. Therefore, an understanding of the factors required for the efficient, selective, and safe delivery of siRNA is a great challenge for successful siRNA delivery. Herein, we report on the development of two pH-sensitive cationic lipids and their use in examining the impact of the acid dissociation constant (pKa) value, lipase sensitivity and the size of lipid nanoparticles on the biodistribution, and efficiency and cell specificity of gene silencing in the liver. An increase in the pKa value resulted in a significant change in the intrahepatic localization of siRNA and gene-silencing efficiency in hepatocytes and liver sinusoidal endothelial cells (LSECs). The sensitivity of the pH-sensitive cationic lipid to lipases was a major factor in achieving hepatocyte-specific gene silencing. Increasing the particle size can improve the LSEC specificity of gene silencing. As a consequence, we succeeded in developing both a highly efficient, hepatocyte-specific formulation, and the most efficacious LSEC-targeted formulation reported to date. These findings will facilitate the development of more sophisticated siRNA delivery systems.

| S-EPMC4886930 | biostudies-literature

Brain mitochondrial drug delivery: influence of drug physicochemical properties.

Project description:To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH.The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery.The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of -1.41 to 1.37, 0.72 to 2.97, and -0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an increase in Log D for each class of drugs, with the uptake at a given lipophilicity obeying the rank order cationic>anionic>neutral. Valinomycin reduced membrane potential and the delivery of positively charged propranolol and betaxolol. The best equation for the combined data set was Log % Uptake?=?0.333 Log D?+?0.157 Charge - 0.887 Log PSA?+?2.032 (R(2)?=?0.738).Drug lipopohilicity, charge, and polar surface area and membrane potential influence mitochondrial drug delivery, with the uptake of positively charged, lipophilic molecules being the most efficient.

| S-EPMC5510476 | biostudies-literature

Self-Assembled Benznidazole-Loaded Cationic Nanoparticles Containing Cholesterol/Sialic Acid: Physicochemical Properties, In Vitro Drug Release and In Vitro Anticancer Efficacy.

Project description:Cationic polymeric nanoparticles (NPs) have the ability to overcome biological membranes, leading to improved efficacy of anticancer drugs. The modulation of the particle-cell interaction is desired to control this effect and avoid toxicity to normal cells. In this study, we explored the surface functionalization of cationic polymethylmethacrylate (PMMA) NPs with two natural compounds, sialic acid (SA) and cholesterol (Chol). The performance of benznidazole (BNZ) was assessed in vitro in the normal renal cell line (HEK-293) and three human cancer cell lines, as follows: human colorectal cancer (HT-29), human cervical carcinoma (HeLa), and human hepatocyte carcinoma (HepG2). The structural properties and feasibility of NPs were evaluated and the changes induced by SA and Chol were determined by using multiple analytical approaches. Small (<200 nm) spherical NPs, with a narrow size distribution and high drug-loading efficiency were prepared by using a simple and reproducible emulsification solvent evaporation method. The drug interactions in the different self-assembled NPs were assessed by using Fourier transform-infrared spectroscopy. All formulations exhibited a slow drug-release profile and physical stability for more than 6 weeks. Both SA and Chol changed the kinetic properties of NPs and the anticancer efficacy. The feasibility and potential of SA/Chol-functionalized NPs has been demonstrated in vitro in the HEK-293, HepG2, HeLa, and HT-29 cell lines as a promising system for the delivery of BNZ.

| S-EPMC6539689 | biostudies-literature

Physicochemical properties and in vitro cytotoxicity of iron oxide-based nanoparticles modified with antiangiogenic and antitumor peptide A7R.

Project description:Superparamagnetic iron oxide-based nanoparticles (SPIONs) are promising carriers as targeted drug delivery vehicles, because they can be guided to their target with the help of an external magnetic field. Functionalization of nanoparticles' surface with molecules, which bind with high affinity to receptors on target tissue significantly facilitates delivery of coated nanoparticles to their targeted site. Here, we demonstrate conjugation of an antiangiogenic and antitumor peptide ATWLPPR (A7R) to SPIONs modified with sebacic acid (SPIONs-SA). Successful conjugation was confirmed by various analytical techniques (FTIR, SERS, SEM-EDS, TEM, TGA). Cell cytotoxicity studies, against two cell lines (HUVEC and MDA-MB-231) indicated that SPIONs modified with A7R reduced HUVEC cell viability at concentrations higher than 0.01 mg Fe/mL, in comparison to cells that were exposed to either the nanoparticles modified with sebacic acid or A7R peptide solely, what might be partially caused by a process of internalization.

| S-EPMC5406482 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data