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AAPS PharmSciTech. 2005 December; 6(4): E565–E572.
Published online 2005 October 31. doi:  10.1208/pt060471
PMCID: PMC2750604

In vitro and in vivo evaluation of topical formulations of Spantide II

Abstract

The purpose of this study was to develop and evaluate topical formulations of Spantide II, a neurokinin-1 receptor (NK-1R) antagonist, for the treatment of inflammatory skin disorders. Spantide II lotion and gel was formulated with and without n-methyl-2-pyrrolidone (NMP) as a penetration enhancer. The release of Spantide II from gels was evaluated using microporous polyethylene and polypropylene membranes in a Franz Diffusion cell setup. In vitro percutaneous absorption of Spantide II from lotion and gel formulations was evaluated using the above setup by replacing the membranes with hairless rat skin. The in vivo anti-inflammatory activity of Spantide II formulations was evaluated in an allergic contact dermatitis (ACD) mouse model. Among different gels studied, PF127 gel showed highest (70-fold) release of Spantide II compared with hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) gels. Lotion and gel formulations with or without NMP showed no detectable levels of Spantide II in the receiver compartment of the Franz diffusion cell until 24 hours. However, Spantide II showed significant retention in epidermis and dermis from lotion and gel formulations at 24 hours. The dermal levels increased ≈3.5- and 2-fold when the lotion and gel formulations contained NMP as compared with the formulation with no NMP (P<.05). The in vivo studies indicated that Spantide II formulations with NMP were effective in significantly reducing ACD response, similar to dexamethasone (0.5 mM). In conclusion, Spantide II was stable as a topical formulation and delivered to target skin tissue (epidermis and dermis) for the treatment of ACD. In addition this study supports the role of cutaneous neurosensory system in modulating inflammatory responses in the skin.

Keywords: Spantide II, peptide, skin permeation, dermatitis, gel, lotion

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Behl C, Char HS, Patel SB, Mehta DB, Piemontese D, Malick AW. In vivo and in vitro skin uptake and permeation studies; critical considerations and factors, which affect them. In: Shah BP, Maibach HI, editors. Topical Drug Bioavailability, Bioequivalence and Penetration. New York, NY: Plenum Press; 1993. pp. 225–259.
2. Marjukka Suhonen T, Bouwstra JA, Urtti A. Chemical enhancement of percutaneous absorption in relation to stratum corneum structural alterations. J Control Release. 1999;59:149–161. doi: 10.1016/S0168-3659(98)00187-4. [PubMed] [Cross Ref]
3. Green PG, Flanagan M, Shroot B, Guy RH. Iontophoretic drug delivery. In: Walters KA, Hadgraft J, editors. Pharmaceutical Skin Penetration Enhancement. New York, NY: Marcel Dekker; 1993. pp. 311–333.
4. Gordon RD, Peterson TA. Myths about transdermal drug delivery. Drug Deliv Technol. 2003;3:1–4.
5. Tian J, Yin CH. In vitro and in vivo assessment of liposomes containing recombinant human interleukin-2. Proc Int Symp Control Release Bioact Mate. 1998;25:439–440.
6. Hora MS, Rana RK, Nunberg JH, Tice TR, Gilley RM, Hudson ME. Controlled release of interleukin-2 from biodegradable microspheres. Biotechnology (N Y) 1990;8:755–758. doi: 10.1038/nbt0890-755. [PubMed] [Cross Ref]
7. Johnston TP, Punjabi MA, Froelich CJ. Sustained delivery of interleukin from poloxamer 407 gel matrix following intraperitoneal injection in mice. Pharm Res. 1992;9:425–434. doi: 10.1023/A:1015815624334. [PubMed] [Cross Ref]
8. Hennink W, Franssen EO, Dijk-Wolthuis WNE, Talsma H. Dextran hydrogels for the controlled release of proteins. J Control Release. 1997;48:107–114. doi: 10.1016/S0168-3659(97)00047-3. [Cross Ref]
9. Morishita M, Barichello JM, Takayama K, Chiba Y, Tokiwa S, Nagai T. Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin. Int J Pharm. 2001;212:289–293. doi: 10.1016/S0378-5173(00)00615-3. [PubMed] [Cross Ref]
10. Stratton LP, Dong A, Manning M, Carpenter JF. Drug delivery matrix containing native protein precipitates suspended in a poloxamer gel. J Pharm Sci. 1997;86:1006–1010. doi: 10.1021/js970034d. [PubMed] [Cross Ref]
11. Wenzel JG, Balaji KS, Koushik K, et al. Pluronic F127 gel formulations of deslorelin and GnRH reduce drug degradation and sustain drug release and effect in cattle. J Control Release. 2002;85:51–59. doi: 10.1016/S0168-3659(02)00271-7. [PubMed] [Cross Ref]
12. Wang P, Johnston TP. Enhanced stability of two model proteins in an agitated solution environment using poloxamer 407. J Parenter Sci Technol. 1993;47:183–189. [PubMed]
13. Babu RJ, Kikwai L, Jaiani LT, et al. Percutaneous absorption and anti-inflammatory effect of a substance P receptor antagonist: Spantide II. Pharm Res. 2004;21:108–113. doi: 10.1023/B:PHAM.0000012157.80716.73. [PubMed] [Cross Ref]
14. Higuchi WI. Analysis of data on the medicament release from ointments. J Pharm Sci. 1962;51:802–804. doi: 10.1002/jps.2600510825. [PubMed] [Cross Ref]
15. Guy RH, Hadgraft J. The determination of drug release rates from topical dosage forms. Int J Pharm. 1990;60:R1–R3. doi: 10.1016/0378-5173(90)90306-O. [Cross Ref]
16. Katakam M, Bell LN, Banga AK. Effect of surfactants on the physical stability of recombinant human growth hormone. J Pharm Sci. 1995;84:713–716. doi: 10.1002/jps.2600840609. [PubMed] [Cross Ref]
17. Schmolka IR. Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res. 1972;6:571–582. doi: 10.1002/jbm.820060609. [PubMed] [Cross Ref]
18. Attwood D, Colett JH, Tait CJ. The micellar properties of poly (oxyethylene)-poly(oxypropylene) copolymer F127 in water and electrolyte solution. Int J Pharm. 1985;26:25–33. doi: 10.1016/0378-5173(85)90197-8. [Cross Ref]
19. Ho HO, Huang FC, Sokoloski TD, Sheu MT. The influence of cosolvents on the in vitro percutaneous penetration of diclofenac sodium from a gel system. J Pharm Pharmacol. 1994;46:636–642. [PubMed]
20. Miller KL, Rao YH, Goodwin SR, Westermann-Clark GB, Shah DO. Solubility and in vitro percutaneous absorption of tetracaine from solvents of propylene glycol and saline. Int J Pharm. 1993;98:101–111. doi: 10.1016/0378-5173(93)90046-I. [Cross Ref]
21. Goodman M, Barry BW. Action of penetration enhancers on human stratum corneum as assessed by differential scanning calorimetry. In: Bronaugh RL, Maibach HI, editors. Percutaneous Absorption, Mechanisms, Methodology, Drug Delivery. New York, NY: Marcel Dekker; 1989. pp. 567–593.
22. Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56:603–618. doi: 10.1016/j.addr.2003.10.025. [PubMed] [Cross Ref]
23. Yoneto K, Ghanem AH, Higuchi WI, Peck KD, Li SK. Mechanistic studies of the 1-alkyl-2-pyrrolidones as skin permeation enhancers. J Pharm Sci. 1995;84:312–317. doi: 10.1002/jps.2600840310. [PubMed] [Cross Ref]
24. Godwin DA, Michniak BB, Player MP, Sowell JW. Transdermal and dermal enhancing activity of pyrrolidones in hairless mouse skin. Int J Pharm. 1997;155:241–250. doi: 10.1016/S0378-5173(97)00163-4. [Cross Ref]
25. Barry BW. Mode of action of penetration enhancers in human skin. J Control Release. 1987;6:85–97. doi: 10.1016/0168-3659(87)90066-6. [Cross Ref]
26. Nair V, Panchagnula R. Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats. Pharmacol Res. 2003;47:555–562. doi: 10.1016/S1043-6618(03)00043-4. [PubMed] [Cross Ref]
27. Desai SD, Blanchard J. In vitro evaluation of Pluronic F127-based controlled-release ocular delivery systems for pilocarpine. J Pharm Sci. 1998;87:226–230. doi: 10.1021/js970090e. [PubMed] [Cross Ref]

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