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

Overview

Journal Gels

Date 2019 Mar 29

PMID 30920519

Citations 4

Authors

Monica Argenziano

Chiara Dianzani

Benedetta Ferrara

Shankar Swaminathan

Amedea Manfredi

Elisabetta Ranucci

Roberta Cavalli

Paolo Ferruti

Affiliations

Soon will be listed here.

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, 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 10⁻10 M concentration range, while dexamethasone was effective only at 10 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.

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References

Meager A . Cytokine regulation of cellular adhesion molecule expression in inflammation. Cytokine Growth Factor Rev. 1999; 10(1):27-39. DOI: 10.1016/s1359-6101(98)00024-0. View

Iniguez M, Punzon C, Fresno M . Induction of cyclooxygenase-2 on activated T lymphocytes: regulation of T cell activation by cyclooxygenase-2 inhibitors. J Immunol. 1999; 163(1):111-9. View

De Gregorio R, Iniguez M, Fresno M, Alemany S . Cot kinase induces cyclooxygenase-2 expression in T cells through activation of the nuclear factor of activated T cells. J Biol Chem. 2001; 276(29):27003-9. DOI: 10.1074/jbc.M100885200. View

DAlessio P . Endothelium as a pharmacological target. Curr Opin Investig Drugs. 2002; 2(12):1720-4. View

De Bosscher K, Vanden Berghe W, Haegeman G . The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev. 2003; 24(4):488-522. DOI: 10.1210/er.2002-0006. View

Szmitko P, Wang C, Weisel R, Jeffries G, Anderson T, Verma S . Biomarkers of vascular disease linking inflammation to endothelial activation: Part II. Circulation. 2003; 108(17):2041-8. DOI: 10.1161/01.CIR.0000089093.75585.98. View

Minneci P, Deans K, Banks S, Eichacker P, Natanson C . Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med. 2004; 141(1):47-56. DOI: 10.7326/0003-4819-141-1-200407060-00014. View

Schottenfeld D, Beebe-Dimmer J . Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin. 2006; 56(2):69-83. DOI: 10.3322/canjclin.56.2.69. View

Zhang D, Marconi A, Xu L, Yang C, Sun G, Feng X . Tripterine inhibits the expression of adhesion molecules in activated endothelial cells. J Leukoc Biol. 2006; 80(2):309-19. DOI: 10.1189/jlb.1005611. View

10.

Cavalli R, Trotta F, Trotta M, Pastero L, Aquilano D . Effect of alkylcarbonates of gamma-cyclodextrins with different chain lengths on drug complexation and release characteristics. Int J Pharm. 2007; 339(1-2):197-204. DOI: 10.1016/j.ijpharm.2007.03.001. View

11.

Doile M, Fortunato K, Schmucker I, Schucko S, Silva M, Rodrigues P . Physicochemical properties and dissolution studies of dexamethasone acetate-beta-cyclodextrin inclusion complexes produced by different methods. AAPS PharmSciTech. 2008; 9(1):314-21. PMC: 2976901. DOI: 10.1208/s12249-008-9042-z. View

12.

Kerachian M, Cournoyer D, Harvey E, Chow T, Neagoe P, Sirois M . Effect of high-dose dexamethasone on endothelial haemostatic gene expression and neutrophil adhesion. J Steroid Biochem Mol Biol. 2009; 116(3-5):127-33. DOI: 10.1016/j.jsbmb.2009.05.001. View

13.

Kabanov A, Vinogradov S . Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem Int Ed Engl. 2009; 48(30):5418-29. PMC: 2872506. DOI: 10.1002/anie.200900441. View

14.

Li M, Chen F, Liu C, Li D, Li X, Wang C . Dexamethasone enhances trichosanthin-induced apoptosis in the HepG2 hepatoma cell line. Life Sci. 2009; 86(1-2):10-6. DOI: 10.1016/j.lfs.2009.10.016. View

15.

Bhardwaj U, Burgess D . Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone. Int J Pharm. 2010; 388(1-2):181-9. DOI: 10.1016/j.ijpharm.2010.01.003. View

16.

Dianzani C, Minelli R, Mesturini R, Chiocchetti A, Barrera G, Boscolo S . B7h triggering inhibits umbilical vascular endothelial cell adhesiveness to tumor cell lines and polymorphonuclear cells. J Immunol. 2010; 185(7):3970-9. DOI: 10.4049/jimmunol.0903269. View

17.

Rafie F, Javadzadeh Y, Javadzadeh A, Alizadeh Ghavidel L, Jafari B, Moogooee M . In vivo evaluation of novel nanoparticles containing dexamethasone for ocular drug delivery on rabbit eye. Curr Eye Res. 2010; 35(12):1081-9. DOI: 10.3109/02713683.2010.508867. View

18.

Jansook P, Ritthidej G, Ueda H, Stefansson E, Loftsson T . yCD/HPyCD mixtures as solubilizer: solid-state characterization and sample dexamethasone eye drop suspension. J Pharm Pharm Sci. 2010; 13(3):336-50. DOI: 10.18433/j3m88b. View

19.

Ruiz-Irastorza G, Danza A, Khamashta M . Glucocorticoid use and abuse in SLE. Rheumatology (Oxford). 2012; 51(7):1145-53. DOI: 10.1093/rheumatology/ker410. View

20.

Moya-Ortega M, Alvarez-Lorenzo C, Concheiro A, Loftsson T . Cyclodextrin-based nanogels for pharmaceutical and biomedical applications. Int J Pharm. 2012; 428(1-2):152-63. DOI: 10.1016/j.ijpharm.2012.02.038. View