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

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 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, ? or ?-CD/PAA nanogels have been developed. In vitro studies showed that a pretreatment for 24?48 h with dexamethasone-loaded, ?-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.

SUBMITTER: Argenziano M

PROVIDER: S-EPMC6318607 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Argenziano Monica M Dianzani Chiara C Ferrara Benedetta B Swaminathan Shankar S Manfredi Amedea A Ranucci Elisabetta E Cavalli Roberta R Ferruti Paolo P

Gels (Basel, Switzerland) 20170608 2

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 cros ...[more]

PMID: 30920519

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Project description:Hydrogels possess a unique three-dimensional, cross-linked network of polymers capable of absorbing large amounts of water and biological fluids without dissolving. Nanohydrogels (NGs) or nanogels are composed of diverse types of polymers of synthetic or natural origin. Their combination is bound by a chemical covalent bond or is physically cross-linked with non-covalent bonds like electrostatic interactions, hydrophobic interactions, and hydrogen bonding. Its remarkable ability to absorb water or other fluids is mainly attributed to hydrophilic groups like hydroxyl, amide, and sulphate, etc. Natural biomolecules such as protein- or peptide-based nanohydrogels are an important category of hydrogels which possess high biocompatibility and metabolic degradability. The preparation of protein nanohydrogels and the subsequent encapsulation process generally involve use of environment friendly solvents and can be fabricated using different proteins, such as fibroins, albumin, collagen, elastin, gelatin, and lipoprotein, etc. involving emulsion, electrospray, and desolvation methods to name a few. Nanohydrogels are excellent biomaterials with broad applications in the areas of regenerative medicine, tissue engineering, and drug delivery due to certain advantages like biodegradability, biocompatibility, tunable mechanical strength, molecular binding abilities, and customizable responses to certain stimuli like ionic concentration, pH, and temperature. The present review aims to provide an insightful analysis of protein/peptide nanohydrogels including their preparation, biophysiochemical aspects, and applications in diverse disciplines like in drug delivery, immunotherapy, intracellular delivery, nutraceutical delivery, cell adhesion, and wound dressing. Naturally occurring structural proteins that are being explored in protein nanohydrogels, along with their unique properties, are also discussed briefly. Further, the review also covers the advantages, limitations, overview of clinical potential, toxicity aspects, stability issues, and future perspectives of protein nanohydrogels.

Project description:The electrospinning of hydrocortisone/cyclodextrin complex nanofibers was performed in order to develop a fast-dissolving oral drug delivery system. Hydrocortisone is a water-insoluble hydrophobic drug, yet, the water solubility of hydrocortisone was significantly enhanced by inclusion complexation with hydroxypropyl-beta-cyclodextrin (HP-β-CyD). In this study, hydrocortisone/HP-β-CyD complexes were prepared in aqueous solutions having molar ratios of 1/1, 1/1.5 and 1/2 (hydrocortisone/HP-β-CyD). Highly concentrated aqueous solutions of HP-β-CyD (180%, w/v) were used for hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) in order to perform electrospinning without the use of an additional polymer matrix. The turbidity of hydrocortisone/HP-β-CyD (1/1 and 1/1.5) aqueous solutions indicated the presence of some uncomplexed crystals of hydrocortisone whereas the aqueous solution of hydrocortisone/HP-β-CyD (1/2) was homogeneous indicating that hydrocortisone becomes totally water-soluble by inclusion complexation with HP-β-CyD. Nonetheless, the electrospinning of hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) successfully yielded defect-free uniform nanofibrous structures. Moreover, the electrospinning process was quite efficient that hydrocortisone was completely preserved without any loss yielding hydrocortisone/HP-β-CyD nanofibers having the initial molar ratios (1/1, 1/1.5 and 1/2). The structural and thermal characterization of the hydrocortisone/HP-β-CyD nanofibers revealed that hydrocortisone was totally inclusion complexed with HP-β-CyD and was in the amorphous state in hydrocortisone/HP-β-CyD (1/2) nanofibers whereas some uncomplexed crystalline hydrocortisone was present in hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibers. Nevertheless, hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) complex aqueous systems were electrospun in the form of nanofibrous webs having a free-standing and flexible nature. The hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibrous webs have shown fast-dissolving behavior in water or when they were in contact with artificial saliva. Yet, the hydrocortisone/HP-β-CyD (1/2) nanofibrous web dissolved more quickly than the hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibrous webs due to the full inclusion complexation and the amorphous state of hydrocortisone in this sample. In short, the results suggest that polymer-free electrospun nanofibrous webs produced from hydrocortisone/HP-β-CyD could be quite applicable for fast-dissolving oral drug delivery systems.

Dataset Information

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

Publications

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

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