scholarly journals Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

2016 ◽  
Vol 2 (5) ◽  
pp. e1600519 ◽  
Author(s):  
Malgosia M. Pakulska ◽  
Irja Elliott Donaghue ◽  
Jaclyn M. Obermeyer ◽  
Anup Tuladhar ◽  
Christopher K. McLaughlin ◽  
...  
Keyword(s):  
Controlled Release ◽  
Electrostatic Interactions ◽  
Underlying Mechanism ◽  
Plga Nanoparticles ◽  
Protein Therapeutics ◽  
Polymer Particles ◽  
Protein Activity ◽  
Tunable Release ◽  
Effective Delivery ◽  
Therapeutic Molecules

Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules.

Understanding Bacterial Ice Nucleation

2021 ◽  
Author(s):  
Ralph Schwidetzky ◽  
Max Lukas ◽  
Anna T. Kunert ◽  
Ulrich Pöschl ◽  
Janine Fröhlich-Nowoisky ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Affinity Purification ◽  
Hydration Shell ◽  
Three Dimensional ◽  
American Chemical Society ◽  
Chemical Society ◽  
Ice Nucleation ◽  
Dimensional Structure ◽  
Protein Activity ◽  
Ice Nucleators

<p>Bacterial ice-nucleating proteins (INPs) promote heterogeneous ice nucleation better than any known material. On the molecular scale, bacterial INPs are believed to function by organizing water into ice‑like patterns to enable the formation of embryonic crystals. However, the details of their working mechanism remains largely elusive. Here, we report the results of comprehensive evaluations of environmentally relevant effects such as changes in pH, the presence of ions and temperature on the activity, three-dimensional structure and hydration shell of bacterial ice nucleators using ice affinity purification, high-throughput ice nucleation assays and surface-specific sum-frequency generation spectroscopy.</p><p> </p><p>[1] Lukas, Max, et al. "Electrostatic Interactions Control the Functionality of Bacterial Ice Nucleators." Journal of the American Chemical Society 142.15 (2020): 6842-6846.</p><p>[2] Lukas, Max, et al. "Interfacial Water Ordering Is Insufficient to Explain Ice-Nucleating Protein Activity." The Journal of Physical Chemistry Letters 12 (2020): 218-223.</p>

scholarly journals Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 93 ◽  
Author(s):  
Eugene P. Chung ◽  
Jennifer D. Cotter ◽  
Alesia V. Prakapenka ◽  
Rebecca L. Cook ◽  
Danielle M. DiPerna ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Rabies Virus ◽  
Trigeminal Nerve ◽  
Intranasal Administration ◽  
Plga Nanoparticles ◽  
Rabies Virus Glycoprotein ◽  
Virus Glycoprotein ◽  
Targeted Nanoparticles ◽  
Effective Delivery

Alternative routes of administration are one approach that could be used to bypass the blood–brain barrier (BBB) for effective drug delivery to the central nervous system (CNS). Here, we focused on intranasal delivery of polymer nanoparticles. We hypothesized that surface modification of poly(lactic-co-glycolic acid) (PLGA) nanoparticles with rabies virus glycoprotein (RVG29) would increase residence time and exposure of encapsulated payload to the CNS compared to non-targeted nanoparticles. Delivery kinetics and biodistribution were analyzed by administering nanoparticles loaded with the carbocyanine dye 1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindotricarbocyanine Iodide (DiR) to healthy mice. Intranasal administration yielded minimal exposure of nanoparticle payload to most peripheral organs and rapid, effective delivery to whole brain. Regional analysis of payload delivery within the CNS revealed higher delivery to tissues closest to the trigeminal nerve, including the olfactory bulb, striatum, midbrain, brainstem, and cervical spinal cord. RVG29 surface modifications presented modest targeting benefits to the striatum, midbrain, and brainstem 2 h after administration, although targeting was not observed 30 min or 6 h after administration. Payload delivery to the trigeminal nerve was 3.5× higher for targeted nanoparticles compared to control nanoparticles 2 h after nanoparticle administration. These data support a nose-to-brain mechanism of drug delivery that closely implicates the trigeminal nerve for payload delivery from nanoparticles via transport of intact nanoparticles and eventual diffusion of payload. Olfactory and CSF routes are also observed to play a role. These data advance the utility of targeted nanoparticles for nose-to-brain drug delivery of lipophilic payloads and provide mechanistic insight to engineer effective delivery vectors to treat disease in the CNS.

scholarly journals The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

2018 ◽  
Vol 20 (1) ◽  
pp. 102 ◽  
Author(s):  
Justine Habibian ◽  
Bradley Ferguson
Keyword(s):  
Gene Expression ◽  
Protein Phosphorylation ◽  
Cross Talk ◽  
Electrostatic Interactions ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Protein Activity ◽  
Histone Protein ◽  
Signal Transduction Protein ◽  
And Function

Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.S. adults projected to suffer from HF by 2030. With five-year mortality rates following HF diagnosis approximating 50%, novel therapeutic treatments are needed for HF patients. Pre-clinical animal models of HF have highlighted histone deacetylase (HDAC) inhibitors as efficacious therapeutics that can stop and potentially reverse cardiac remodeling and dysfunction linked with HF development. HDACs remove acetyl groups from nucleosomal histones, altering DNA-histone protein electrostatic interactions in the regulation of gene expression. However, HDACs also remove acetyl groups from non-histone proteins in various tissues. Changes in histone and non-histone protein acetylation plays a key role in protein structure and function that can alter other post translational modifications (PTMs), including protein phosphorylation. Protein phosphorylation is a well described PTM that is important for cardiac signal transduction, protein activity and gene expression, yet the functional role for acetylation-phosphorylation cross-talk in the myocardium remains less clear. This review will focus on the regulation and function for acetylation-phosphorylation cross-talk in the heart, with a focus on the role for HDACs and HDAC inhibitors as regulators of acetyl-phosphorylation cross-talk in the control of cardiac function.

scholarly journals A new paradigm for antiangiogenic therapy through controlled release of bevacizumab from PLGA nanoparticles

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Flávia Sousa ◽  
Andrea Cruz ◽  
Pedro Fonte ◽  
Inês Mendes Pinto ◽  
Maria Teresa Neves-Petersen ◽  
...  
Keyword(s):  
Controlled Release ◽  
Antiangiogenic Therapy ◽  
Plga Nanoparticles ◽  
New Paradigm

scholarly journals A Bioinspired Platform for Effective Delivery of Protein Therapeutics to the Central Nervous System

2019 ◽  
Vol 31 (18) ◽  
pp. 1807557 ◽  
Author(s):  
Di Wu ◽  
Meng Qin ◽  
Duo Xu ◽  
Lan Wang ◽  
Chaoyong Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Therapeutics ◽  
Effective Delivery ◽  
The Central Nervous System

'Plate‐like‐coral' polymer particles with dendritic structure and porous channels: Effective delivery of anti‐cancer drugs

2020 ◽  
pp. 50386
Author(s):  
Chander Amgoth ◽  
Gangappa Dharmapuri ◽  
Sukanya Patra ◽  
Kirti Wasnik ◽  
Premshankar Gupta ◽  
...  
Keyword(s):  
Dendritic Structure ◽  
Cancer Drugs ◽  
Polymer Particles ◽  
Anti Cancer ◽  
Effective Delivery ◽  
Porous Channels

scholarly journals Construction of an Effective Delivery System for DNA Vaccines Using Biodegradable Polylactic Acid Based Microspheres

2020 ◽  
Author(s):  
Shuaikai Ren ◽  
Liang Guo ◽  
Chunxin Wang ◽  
Jiaxi Ru ◽  
Yunqi Yang ◽  
...  
Keyword(s):  
Polylactic Acid ◽  
Dna Vaccine ◽  
Delivery System ◽  
Plasmid Dna ◽  
Electrostatic Interactions ◽  
Dna Vaccines ◽  
Transfection Efficiency ◽  
Control Group ◽  
Surface Charges ◽  
Effective Delivery

Abstract Background: Nanotechnology represents a new impetus for biomedical research applications, especially using nanotechnology to formulate microspheres or nanospheres based delivery system for treatment of infectious diseases in animals.Results: Polylactic acid (PLA) microspheres with an average size of 156nm were prepared by combining emulsion polymerization coupled with emulsion−solvent evaporation. Coating with three different molecular weights of polyethylenimine (PEI) polymers increased the surface charges of the resulting PLA/PEI microspheres. Electrostatic interactions enabled plasmid DNA to adsorb tightly to the microspheres. After pig kidney-15 cells were cultured with the PLA/PEI/DNA complexes for 48 h, all three PLA/PEI microspheres successfully transferred plasmid DNA into the cells with high transfection efficiency. The protection rate of PLA/PEI microspheres loaded with DNA vaccine against foot-and-mouth disease in guinea pigs reached 87.5%, which was significantly higher than that of the control group injected with only DNA vaccine.Conclusions: In this work, PLA/PEI microspheres were constructed by preparing PLA microspheres and modifying with PEI polymers, and were shown a great potential in improve the efficacy, biosafety and economic effects of DNA vaccines. The results indicated PLA/PEI microspheres were expected to be an effective delivery system for DNA vaccines.

scholarly journals Unveiling the Key Templates in the Self-Assembly of Gigantic Molybdenum Blue Wheels

2018 ◽  
Author(s):  
Weimin Xuan ◽  
Robert Pow ◽  
Qi Zheng, ◽  
Nancy Watfa ◽  
De-Liang Long ◽  
...  
Keyword(s):  
Self Assembly ◽  
Electrostatic Interactions ◽  
Structural Evolution ◽  
Functional Materials ◽  
Building Blocks ◽  
Underlying Mechanism ◽  
The Self ◽  
Supramolecular Systems ◽  
Structure Directing Agent ◽  
Molybdenum Blue

Template synthesis is a powerful and useful approach to build a variety of functional materials and complicated supramolecular systems. Systematic study on how templates structurally evolve from basic building blocks and then affect the templated self-assembly is critical to understand the underlying mechanism and gain more guidance for designed assembly but remains challenging. Here we describe the templated self-assembly of a series of gigantic Mo Blue (MB) clusters 1-4 using L-ornithine as structure-directing agent. L-ornithine is essential for the formation of such kind of template⊂host assemblies by providing directional forces of hydrogen bonding and electrostatic interactions. Based on the structural relationship between encapsulated templates of {Mo8} (1), {Mo17} (2) and {Mo36} (4), a plausible pathway of the structural evolution of templates is proposed, thus giving more insight on the templated self-assembly of Mo Blue clusters.

scholarly journals Nanotechnological innovation for the production of daughter less Tilapia, Oreochromis niloticus (Linnaeus, 1758)

2017 ◽  
Vol 9 (4) ◽  
pp. 1921-1925
Author(s):  
Harshavardhan D. Joshi ◽  
V. K. Tiwari ◽  
Rupam Sharma ◽  
Subodh Gupta ◽  
W. S. Lakra ◽  
...  
Keyword(s):  
Particle Size ◽  
Oreochromis Niloticus ◽  
Sex Differentiation ◽  
Plga Nanoparticles ◽  
Duration Of Treatment ◽  
Male Population ◽  
Effective Delivery ◽  
Series Of Experiments ◽  
Average Size ◽  
Differentiation Period

The aim of present work was to develop a new Fadrozole (FDZ)-loaded Poly (D,L-lactide-co– glycolide) lactide:glycolide (50:50)(PLGA) nanoparticles for effective delivery of the masculinization drug, Fadrozole, as an alternative to commercially available masculinization agents like testosterone (dietary supplementation of 17 α- methyltestosterone) which are steroids and banned in most EU countries. The FDZ-loaded PLGA NPs were pre-pared by solvent displacement technique. The particle size of FDZ-loaded PLGA NPs was analyzed using LICOMP particle size analyser. It was found to be in the range of 60±66.7 nm to 560±66.7 nm with average size of 201.4±66.7 nm, where the Zeta potential was estimated to be about -20.82 mV, a series of experiments were carried out to induce masculinization using FDZ-loaded PLGA nanoparticles during the sex differentiation period. Tilapia, Oreochromis niloticus fry were treated with FTZ-loaded PLGA nanoparticles at dosages 5, 25, 50 and 100ppm/kg diet for 10, 15 and 30 days. The results indicated an increase in the proportion of males with dosage and duration of treatment. The male percentage was 92.35±0.86 for T7(50 ppm) at 10 days, 97.76±1.12 for T7 (100 ppm) at 15 days and 100 % for both T6 (50ppm) and T7 (100 ppm) at 30 days. This is first time done by using nanotechnology efficiently in Tilapia species which is very important Fresh water aquaculture species in present era. Which showed increase the male population with lesser dose of nano-encapsulated Fadrozole (FDZ) loaded PLGA nanoparticles drug as compared with naked control Fadrozole (FDZ) drug delivery.

scholarly journals Synergistical Use of Electrostatic and Hydrophobic Interactions for the Synthesis of a New Class of Multifunctional Nanohybrids: Plasmonic Magneto-Liposomes

Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1623 ◽  
Author(s):  
Gabriela Fabiola Știufiuc ◽  
Ștefan Nițică ◽  
Valentin Toma ◽  
Cristian Iacoviță ◽  
Dietrich Zahn ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Raman Spectroscopy ◽  
Controlled Release ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Superparamagnetic Iron Oxide ◽  
Surface Enhanced Raman Spectroscopy ◽  
New Class

By carefully controlling the electrostatic interactions between cationic liposomes, which already incorporate magnetic nanoparticles in the bilayers, and anionic gold nanoparticles, a new class of versatile multifunctional nanohybrids (plasmonic magneto-liposomes) that could have a major impact in drug delivery and controlled release applications has been synthesized. The experimental results confirmed the successful synthesis of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and polyethylene glycol functionalized (PEGylated) gold nanoparticles (AuNPs). The SPIONs were incorporated in the liposomal lipidic bilayers, thus promoting the formation of cationic magnetoliposomes. Different concentrations of SPIONs were loaded in the membrane. The cationic magnetoliposomes were decorated with anionic PEGylated gold nanoparticles using electrostatic interactions. The successful incorporation of SPIONs together with the modifications they generate in the bilayer were analyzed using Raman spectroscopy. The plasmonic properties of the multifunctional nanohybrids were investigated using UV-Vis absorption and (surface-enhanced) Raman spectroscopy. Their hyperthermic properties were recorded at different frequencies and magnetic field intensities. After the synthesis, the nanosystems were extensively characterized in order to properly evaluate their potential use in drug delivery applications and controlled release as a result of the interaction with an external stimulus, such as an NIR laser or alternating magnetic field.

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