title: Topical delivery of anti-TNFα siRNA and capsaicin via novel lipid-polymer hybrid nanoparticles efficiently inhibits skin inflammation in vivo.
abstract: The barrier properties of the skin pose a significant but not insurmountable obstacle for development of new effective anti-inflammatory therapies. The objective of this study was to design and evaluate therapeutic efficacy of anti-nociception agent Capsaicin (Cap) and anti-TNFα siRNA (siTNFα) encapsulated cyclic cationic head lipid-polymer hybrid nanocarriers (CyLiPns) against chronic skin inflammatory diseases. Physico-chemical characterizations including hydrodynamic size, surface potential and entrapment efficacies of CyLiPns were found to be 163±9nm, 35.14±8.23mV and 92% for Cap, respectively. In vitro skin distribution studies revealed that CyLiPns could effectively deliver FITC-siRNA up to 360μm skin depth. Further, enhanced (p<0.001) Cap permeation from CyLiPns was observed compared to Capsaicin-Solution and Capzasin-HP. Therapeutic efficacies of CyLiPns were assessed using imiquamod-induced psoriatic plaque like model. CyLiPns carrying both Cap and siTNFα showed significant reduced expression of TNFα, NF-κB, IL-17, IL-23 and Ki-67 genes compared to either drugs alone (p<0.05) and were in close comparison with Topgraf®. Collectively these findings support our notion that novel cationic lipid-polymer hybrid nanoparticles can efficiently carry siTNFα and Cap into deeper dermal milieu and Cap with a combination of siTNFα shows synergism in treating skin inflammation.
authors: College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee 32307, USA.
authors: Pinaki R
authors: PR
authors: Desai
authors: Srujan
authors: S
authors: Marepally
authors: Apurva R
authors: AR
authors: Patel
authors: Chandrashekhar
authors: C
authors: Voshavar
authors: Arabinda
authors: A
authors: Chaudhuri
authors: Mandip
authors: M
authors: Singh
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002211:Capsaicin / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D003872:Dermatitis / Q000188:drug therapy* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051381:Rats; D054772:Rats, Hairless; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D020381:Interleukin-17; D053759:Interleukin-23; D019394:Ki-67 Antigen; D008055:Lipids; D016328:NF-kappa B; D011108:Polymers; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D002211:Capsaicin
references: PLoS One. 2011 Mar 15;6(3):e17733
references: 21423660
references: J Clin Pharmacol. 2006 Apr;46(4):418-23
references: 16554449
references: Nature. 2001 May 24;411(6836):494-8
references: 11373684
references: Cell Mol Biol Lett. 2009;14(2):347-62
references: 19194666
references: Exp Dermatol. 2012 Jun;21(6):420-5
references: 22506937
references: J Control Release. 2012 Aug 10;161(3):735-45
references: 22617521
references: Clin Dermatol. 2010 Jan-Feb;28(1):88-92
references: 20082957
references: Pharm Res. 2012 Sep;29(9):2587-600
references: 22644591
references: Crit Rev Ther Drug Carrier Syst. 2010;27(5):419-59
references: 21083529
references: N Engl J Med. 2010 Jan 14;362(2):118-28
references: 20071701
references: J Control Release. 2003 Jan 9;86(1):49-57
references: 12490372
references: J Clin Invest. 1996 Jun 15;97(12):2911-6
references: 8675706
references: J Biol Chem. 1994 Nov 25;269(47):29903-7
references: 7961986
references: Arthritis Rheum. 2005 Apr;52(4):1314-8
references: 15818667
references: Chem Biol. 2004 Apr;11(4):427-37
references: 15123237
references: Arch Dermatol Res. 2012 Mar;304(2):139-44
references: 22009459
references: Biomaterials. 2010 Mar;31(8):2425-34
references: 20034662
references: Arthritis Rheum. 2006 Jun;54(6):1867-77
references: 16729293
references: Expert Opin Biol Ther. 2010 Aug;10(8):1197-208
references: 20560729
references: J Cutan Med Surg. 2009 Sep-Oct;13 Suppl 2:S67-76
references: 19799829
references: Adv Drug Deliv Rev. 2009 Jul 25;61(9):721-31
references: 19328215
references: J Control Release. 2012 Jan 10;157(1):141-8
references: 21864597
references: Indian J Pharm Sci. 2008 Jan;70(1):5-10
references: 20390073
references: Mol Ther. 2009 Jan;17(1):162-8
references: 18827803
references: Angew Chem Int Ed Engl. 2011 Jul 25;50(31):7027-31
references: 21698724
references: J Control Release. 2012 Mar 10;158(2):336-45
references: 22134117
references: Eur J Pharm Biopharm. 2001 Sep;52(2):103-12
references: 11522474
references: FEBS Lett. 2004 Aug 13;572(1-3):266-70
references: 15304360
references: Mol Ther. 2008 Jul;16(7):1323-30
references: 18461054
references: Colloids Surf B Biointerfaces. 2011 Oct 15;87(2):333-9
references: 21684725
references: Adv Drug Deliv Rev. 2004 Mar 27;56(5):603-18
references: 15019749
references: Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):11975-80
references: 22773805
references: Clin Dermatol. 2005 Jul-Aug;23(4):357-64
references: 16023931
references: Am J Health Syst Pharm. 2011 May 1;68(9):795-806
references: 21515863
references: Drug Dev Ind Pharm. 2006 Mar;32(3):267-86
references: 16556532
references: Eur J Pharm Sci. 2001 Sep;14(2):101-14
references: 11500256
references: Nature. 2007 Feb 22;445(7130):866-73
references: 17314973
references: Med Res Rev. 2007 Sep;27(5):696-722
references: 17022036
references: Gene Ther. 2011 May;18(5):496-500
references: 21179175
references: J Control Release. 2011 Jun 30;152(3):330-48
references: 21238514
references: Biomaterials. 2010 Jul;31(21):5598-607
references: 20413152
references: Mol Cancer Ther. 2010 Nov;9(11):3003-14
references: 20978159
references: Nat Mater. 2006 Oct;5(10):791-6
references: 16998471
references: Int J Pharm. 2001 Aug 14;224(1-2):89-104
references: 11472818
references: Mol Ther. 2004 Jun;9(6):829-36
references: 15194049
references: Cell Signal. 2003 Mar;15(3):299-306
references: 12531428
references: Expert Opin Drug Deliv. 2009 Dec;6(12):1333-49
references: 19941411
references: ACS Nano. 2011 Dec 27;5(12):9977-83
references: 22077198
references: J Pharmacol Exp Ther. 2011 Aug;338(2):443-50
references: 21531792
references: Drug Discov Today. 2008 Jun;13(11-12):513-21
references: 18549978
references: Adv Drug Deliv Rev. 2009 Jul 25;61(9):710-20
references: 19356738
references: Int J Mol Sci. 2012;13(1):516-33
references: 22312268
references: J Gene Med. 2009 Jan;11(1):38-45
references: 19021130
references: Mol Membr Biol. 2010 Oct;27(7):247-59
references: 21028936
references: Clin Cosmet Investig Dermatol. 2010 May 25;3:79-84
references: 21437062
references: Biomaterials. 2012 Feb;33(5):1607-17
references: 22118820
references: J Med Chem. 2005 Jun 2;48(11):3784-95
references: 15916430
references: Sci Transl Med. 2010 Oct 6;2(52):52ra72
references: 20926833
references: ACS Nano. 2008 Aug;2(8):1696-702
references: 19206374
references: J Immunol. 2009 May 1;182(9):5836-45
references: 19380832
references: Curr Med Chem. 2000 Jun;7(6):593-608
references: 10702628