Cyclodextrin-based nanosponges for delivery of resveratrol: in vitro characterisation, stability, cytotoxicity and permeation study.
The aim of this work was to increase the solubility, stability and permeation of resveratrol by complexation with cyclodextrin-based nanosponges (NS). Nanosponges are recently developed hyper-cross-linked cyclodextrin polymers nanostructured to form three-dimensional networks; they are obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole. They have been used to increase the solubility and stability of poorly soluble actives. This study aimed at formulating complexes of resveratrol with β-cyclodextrin nanosponges in different weight ratios. DSC, FTIR and X-ray powder diffraction (XRPD) studies confirmed the interaction of resveratrol with NS. XRPD showed that the crystallinity of resveratrol decrease after encapsulation. The particle sizes of resveratrol-loaded NS are in between 400 to 500 nm with low polydispersity indices. Zeta potential is sufficiently high to obtain a stable colloidal nanosuspension. TEM measurement also revealed a particle size around 400 nm for NS complexes. The in vitro release and stability of resveratrol complex were increased compared with plain drug. Cytotoxic studies on HCPC-I cell showed that resveratrol formulations were more cytotoxic than plain resveratrol. The permeation study indicates that the resveratrol NS formulation showed good permeation in pigskin. The accumulation study in rabbit mucosa showed better accumulation of resveratrol NS formulation than plain drug. These results signify that resveratrol NS formulation can be used for buccal delivery and topical application.
Department of Pharmaceutical Sciences and Technology, Centre for Novel Drug Delivery System, Institute of Chemical Technology, Mumbai, India.
Khalid A
KA
Ansari
Pradeep R
PR
Vavia
Francesco
F
Trotta
Roberta
R
Cavalli
D000278:Administration, Buccal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002482:Cellulose / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D049329:Nanostructures; D010316:Particle Size; D010539:Permeability; D011817:Rabbits; D000077185:Resveratrol; D012995:Solubility; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D004337:Drug Carriers; D005079:Excipients; D013267:Stilbenes; D047392:beta-Cyclodextrins; C041953:cyclodextrin polymer; D002482:Cellulose; C031215:betadex; D000077185:Resveratrol
Mol Nutr Food Res. 2005 May;49(5):472-81
15779070
Mol Nutr Food Res. 2005 May;49(5):495-504
15830336
Blood. 1998 Aug 1;92(3):996-1002
9680369
J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Mar 7;832(2):177-80
16446129
Drug Deliv. 2010 Aug;17(6):419-25
20429848
Biochem Pharmacol. 2002 Jan 15;63(2):99-104
11841782
Eur J Endocrinol. 1998 Jun;138(6):619-20
9678525
Biochem Biophys Res Commun. 2009 Jan 16;378(3):389-93
19059213
Nature. 2001 Jun 14;411(6839):843-7
11459067
Lancet. 1992 Jun 20;339(8808):1523-6
1351198
Drugs Exp Clin Res. 1998;24(3):133-8
9825229
J Agric Food Chem. 1999 Apr;47(4):1533-6
10564012
Clin Chim Acta. 1996 Mar 15;246(1-2):163-82
8814965
Eur J Pharm Biopharm. 2010 Feb;74(2):193-201
19900544
AAPS PharmSciTech. 2007 Nov 09;8(4):E94
18181554
Circ Res. 1998 Jun 15;82(11):1111-29
9633912
Science. 1997 Jan 10;275(5297):218-20
8985016