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5707 KiB

Open AccessArticle

Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases

by Monica Argenziano, Chiara Dianzani, Benedetta Ferrara, Shankar Swaminathan, Amedea Manfredi, Elisabetta Ranucci, Roberta Cavalli and Paolo Ferruti

Gels 2017, 3(2), 22; https://doi.org/10.3390/gels3020022 - 08 Jun 2017

Cited by 15 | Viewed by 5400

Abstract

Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both [...] Read more.

Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both bioavailability and duration of the administered drug and reducing the therapeutic dose. Hydrogels are soft materials consisting of water-swollen cross-linked polymers to which the insertion of cyclodextrin (CD) moieties adds hydrophobic drug-complexing sites. Polyamidoamines (PAAs) are biocompatible and biodegradable polymers apt to create CD moieties in hydrogels. In this work, β or γ-CD/PAA nanogels have been developed. In vitro studies showed that a pretreatment for 24–48 h with dexamethasone-loaded, β-CD/PAA nanogel (nanodexa) inhibits adhesion of Jurkat cells to human umbilical vein endothelial cells (HUVEC) in conditions mimicking inflammation. This inhibitory effect was faster and higher than that displayed by free dexamethasone. Moreover, nanodexa inhibited COX-2 expression induced by PMA+A23187 in Jurkat cells after 24–48 h incubation in the 10⁻⁸–10⁻⁵ M concentration range, while dexamethasone was effective only at 10⁻⁵ M after 48 h treatment. Hence, the novel nanogel-dexamethasone formulation combines faster action with lower doses, suggesting the potential for being more manageable than the free drug, reducing its adverse side effects. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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2286 KiB

Open AccessFeature PaperArticle

Design of Hybrid Gels Based on Gellan-Cholesterol Derivative and P90G Liposomes for Drug Depot Applications

by Nicole Zoratto, Francesca Romana Palmieri, Claudia Cencetti, Elita Montanari, Chiara Di Meo, Maria Letizia Manca, Maria Manconi and Pietro Matricardi

Gels 2017, 3(2), 18; https://doi.org/10.3390/gels3020018 - 08 May 2017

Cited by 2 | Viewed by 5009

Abstract

Gels are extensively studied in the drug delivery field because of their potential benefits in therapeutics. Depot gel systems fall in this area, and the interest in their development has been focused on long-lasting, biocompatible, and resorbable delivery devices. The present work describes [...] Read more.

Gels are extensively studied in the drug delivery field because of their potential benefits in therapeutics. Depot gel systems fall in this area, and the interest in their development has been focused on long-lasting, biocompatible, and resorbable delivery devices. The present work describes a new class of hybrid gels that stem from the interaction between liposomes based on P90G phospholipid and the cholesterol derivative of the polysaccharide gellan. The mechanical properties of these gels and the delivery profiles of the anti-inflammatory model drug diclofenac embedded in such systems confirmed the suitability of these hybrid gels as a good candidate for drug depot applications. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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1150 KiB

Open AccessFeature PaperArticle

Impact of Chitosan Molecular Weight and Attached Non-Interactive Chains on the Formation of α-Lactalbumin Nanogel Particles

by Juan Du, Young-Hee Cho, Ryan Murphy and Owen Griffith Jones

Gels 2017, 3(2), 14; https://doi.org/10.3390/gels3020014 - 26 Apr 2017

Cited by 4 | Viewed by 3875

Abstract

Thermal treatment of protein–polysaccharide complexes will form nanogel particles, wherein the polysaccharide controls nanogel formation by limiting protein aggregation. To determine the impact of the chitosan molecular weight and non-interactive chains on the formation of nanogels, mixtures of α-lactalbumin were prepared with selectively-hydrolyzed [...] Read more.

Thermal treatment of protein–polysaccharide complexes will form nanogel particles, wherein the polysaccharide controls nanogel formation by limiting protein aggregation. To determine the impact of the chitosan molecular weight and non-interactive chains on the formation of nanogels, mixtures of α-lactalbumin were prepared with selectively-hydrolyzed chitosan containing covalently-attached polyethylene glycol chains (PEG) and heated near the protein’s isoelectric point to induce formation of nanogels. Turbidity of heated mixtures indicated the formation of suspended aggregates, with greater values observed at higher pH, without attached PEG, and among samples with 8.9 kDa chitosan. Mixtures containing 113 kDa chitosan-PEG formed precipitating aggregates above pH 5, coinciding with a low-magnitude colloidal charge and average hydrodynamic radii > 400 nm. All other tested mixtures were stable to precipitation and possessed average hydrodynamic radii ~100 nm, with atomic force microscopy showing homogeneous distributions of spherical nanogel aggregates. Over all of the tested conditions, attached PEG led to no additional significant changes in the size or morphology of nanogels formed from the protein and chitosan. While PEG may have interfered with the interactions between protein and the 113 kDa chitosan, prompting greater aggregation and precipitation, PEG did not indicate any such interference for shorter chitosan chains. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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6710 KiB

Open AccessFeature PaperArticle

Tacticity-Dependent Interchain Interactions of Poly(N-Isopropylacrylamide) in Water: Toward the Molecular Dynamics Simulation of a Thermoresponsive Microgel

by Gaio Paradossi and Ester Chiessi

Gels 2017, 3(2), 13; https://doi.org/10.3390/gels3020013 - 19 Apr 2017

Cited by 8 | Viewed by 5360

Abstract

The discovery that the lower critical solution temperature (LCST) of poly(N-Isopropylacrylamide) (PNIPAM) in water is affected by the tacticity opens the perspective to tune the volume phase transition temperature of PNIPAM microgels by changing the content of meso dyads in the [...] Read more.

The discovery that the lower critical solution temperature (LCST) of poly(N-Isopropylacrylamide) (PNIPAM) in water is affected by the tacticity opens the perspective to tune the volume phase transition temperature of PNIPAM microgels by changing the content of meso dyads in the polymer network. The increased hydrophobicity of isotactic-rich PNIPAM originates from self-assembly processes in aqueous solutions also below the LCST. The present work aims to detect the characteristics of the pair interaction between polymer chains, occurring in a concentration regime close to the chain overlap concentration, by comparing atactic and isotactic-rich PNIPAM solutions. Using atomistic molecular dynamics simulations, we successfully modelled the increased association ability of the meso-dyad-rich polymer in water below the LCST, and gain information on the features of the interchain junctions as a function of tacticity. Simulations carried out above the LCST display the PNIPAM transition to the insoluble state and do not detect a relevant influence of stereochemistry on the structure of the polymer ensemble. The results obtained at 323 K provide an estimate of the swelling ratio of non-stereocontrolled PNIPAM microgels which is in agreement with experimental findings for microgels prepared with low cross-linker/monomer feed ratios. This study represents the first step toward the atomistic modelling of PNIPAM microgels with a controlled tacticity. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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6168 KiB

Open AccessFeature PaperArticle

Carboxymethyl Cellulose-Grafted Mesoporous Silica Hybrid Nanogels for Enhanced Cellular Uptake and Release of Curcumin

by Neha Tiwari, Laxman Nawale, Dhiman Sarkar and Manohar V. Badiger

Gels 2017, 3(1), 8; https://doi.org/10.3390/gels3010008 - 22 Feb 2017

Cited by 23 | Viewed by 10079

Abstract

Mesoporous silica nanoparticles (MSNs) with ordered pore structure have been synthesized and used as carriers for the anticancer drug curcumin. MSNs were functionalized with amine groups and further attached with carboxymethyl cellulose (CMC) using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) coupling chemistry, which increased the hydrophilicity and [...] Read more.

Mesoporous silica nanoparticles (MSNs) with ordered pore structure have been synthesized and used as carriers for the anticancer drug curcumin. MSNs were functionalized with amine groups and further attached with carboxymethyl cellulose (CMC) using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) coupling chemistry, which increased the hydrophilicity and biocompatibility of MSNs. The functionalized MSNs (MSN-NH₂ and MSN-CMC) were characterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), N₂ adsorption, X-Ray Diffraction (XRD), Thermo Gravimetric Analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of curcumin from the –NH₂ and CMC functionalized MSNs (MSN-cur-NH₂ and MSN-cur-CMC) was performed in 0.5% aqueous solution of sodium lauryl sulphate (SLS). The effect of CMC functionalization of MSNs towards cellular uptake was studied in the human breast cancer cell line MDA-MB-231 and was compared with that of MSN-NH₂ and free curcumin (cur). Both MSN-NH₂ and MSN-CMC showed good biocompatibility with the breast cancer cell line. The MTT assay study revealed that curcumin-loaded MSN-cur-CMC showed better uptake as compared to curcumin-loaded MSN-cur-NH₂. Free curcumin was used as a control and was shown to have much less internalization as compared to the curcumin-loaded functionalized MSNs due to poor bioavailability. Fluorescence microscopy was used to localize the fluorescent drug curcumin inside the cells. The work demonstrates that CMC-functionalized MSNs can be used as potential carriers for loading and release of hydrophobic drugs that otherwise cannot be used effectively in their free form for cancer therapy. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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51502 KiB

Open AccessArticle

Hydrogel Micro-/Nanosphere Coated by a Lipid Bilayer: Preparation and Microscopic Probing

by Sarah Rahni and Sergey Kazakov

Gels 2017, 3(1), 7; https://doi.org/10.3390/gels3010007 - 15 Feb 2017

Cited by 5 | Viewed by 5934

Abstract

The result of polymeric nanogels and lipid vesicles interaction—lipobeads—can be considered as multipurpose containers for future therapeutic applications, such as targeted anticancer chemotherapy with superior tumor response and minimum side effects. In this work, micrometer sized lipobeads were synthesized by two methods: (i) [...] Read more.

The result of polymeric nanogels and lipid vesicles interaction—lipobeads—can be considered as multipurpose containers for future therapeutic applications, such as targeted anticancer chemotherapy with superior tumor response and minimum side effects. In this work, micrometer sized lipobeads were synthesized by two methods: (i) mixing separately prepared microgels made of poly(N-isopropylacrylamide) (PNIPA) and phospholipid vesicles of micrometer or nanometer size and (ii) polymerization within the lipid vesicles. For the first time, a high vacuum scanning electron microscopy was shown to be suitable for a quick validation of the structural organization of wet lipobeads and their constituents without special sample preparation. In particular, the structural difference of microgels prepared by thermal and UV-polymerization in different solvents was revealed and three types of giant liposomes were recognized under high vacuum in conjunction with their size, composition, and method of preparation. Importantly, the substructure of the hydrogel core and multi- and unilamellar constructions of the peripheral lipid part were explicitly distinguished on the SEM images of lipobeads, justifying the spontaneous formation of a lipid bilayer on the surface of microgels and evidencing an energetically favorable structural organization of the hydrogel/lipid bilayer assembly. This key property can facilitate lipobeads’ preparation and decrease technological expenses on their scaled production. The comparison of the SEM imaging with the scanning confocal and atomic force microscopies data are also presented in the discussion. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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Review

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2664 KiB

Open AccessFeature PaperReview

Bioengineering Microgels and Hydrogel Microparticles for Sensing Biomolecular Targets

by Edmondo Battista, Filippo Causa and Paolo Antonio Netti

Gels 2017, 3(2), 20; https://doi.org/10.3390/gels3020020 - 30 May 2017

Cited by 22 | Viewed by 8528

Abstract

Hydrogels, and in particular microgels, are playing an increasingly important role in a diverse range of applications due to their hydrophilic, biocompatible, and highly flexible chemical characteristics. On this basis, solution-like environment, non-fouling nature, easy probe accessibility and target diffusion, effective inclusion of [...] Read more.

Hydrogels, and in particular microgels, are playing an increasingly important role in a diverse range of applications due to their hydrophilic, biocompatible, and highly flexible chemical characteristics. On this basis, solution-like environment, non-fouling nature, easy probe accessibility and target diffusion, effective inclusion of reporting moieties can be achieved, making them ideal substrates for bio-sensing applications. In fact, hydrogels are already successfully used in immunoassays as well as sensitive nucleic acid assays, also enabling hydrogel-based suspension arrays. In this review, we discuss key parameters of hydrogels in the form of micron-sized particles to be used in sensing applications, paying attention to the protein and oligonucleotides (i.e., miRNAs) targets as most representative kind of biomarkers. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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4718 KiB

Open AccessFeature PaperReview

The Potential of Stimuli-Responsive Nanogels in Drug and Active Molecule Delivery for Targeted Therapy

by Marta Vicario-de-la-Torre and Jacqueline Forcada

Gels 2017, 3(2), 16; https://doi.org/10.3390/gels3020016 - 08 May 2017

Cited by 66 | Viewed by 9464

Abstract

Nanogels (NGs) are currently under extensive investigation due to their unique properties, such as small particle size, high encapsulation efficiency and protection of active agents from degradation, which make them ideal candidates as drug delivery systems (DDS). Stimuli-responsive NGs are cross-linked nanoparticles (NPs), [...] Read more.

Nanogels (NGs) are currently under extensive investigation due to their unique properties, such as small particle size, high encapsulation efficiency and protection of active agents from degradation, which make them ideal candidates as drug delivery systems (DDS). Stimuli-responsive NGs are cross-linked nanoparticles (NPs), composed of polymers, natural, synthetic, or a combination thereof that can swell by absorption (uptake) of large amounts of solvent, but not dissolve due to the constituent structure of the polymeric network. NGs can undergo change from a polymeric solution (swell form) to a hard particle (collapsed form) in response to (i) physical stimuli such as temperature, ionic strength, magnetic or electric fields; (ii) chemical stimuli such as pH, ions, specific molecules or (iii) biochemical stimuli such as enzymatic substrates or affinity ligands. The interest in NGs comes from their multi-stimuli nature involving reversible phase transitions in response to changes in the external media in a faster way than macroscopic gels or hydrogels due to their nanometric size. NGs have a porous structure able to encapsulate small molecules such as drugs and genes, then releasing them by changing their volume when external stimuli are applied. Full article

(This article belongs to the Special Issue Micro- and Nanogels)

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