Abstract
The present study focuses on the development and characterization of nanosuspension of a poorly soluble drug, silver sulfadiazine (SSD) incorporated in Aloe vera gel (AV-gel) for improving its therapeutic efficacy. The SSD solution in ammonia was subjected to nanoprecipitation in surfactant solution and particle size was optimized by varying concentration of surfactant. Optimized formulation constituted of 5.5% (w/v) Span 20 and 5.5% (w/v) Tween 80 as a dispersing agent and 0.5% (w/v) Poloxamer 188 as a co-surfactant. The prepared nanosuspension was evaluated for particle size, polydispersity index, surface morphology, and x-ray diffraction study. The optimized nanosuspension was incorporated into nanogel formulation with the addition of 1% AV-gel and 0.5% Carbopol 940 for topical delivery of nanosized SSD. Evaluation of in vitro drug release exhibited a significant enhancement in release rate of the drug from developed nanogel formulation (77.16 ± 3.241%) in comparison to marketed formulation (42.81 ± 1.452%) after 48 h. In vivo histopathological studies in rats for 14 days of application of prepared nanogel showed improvement in the wound healing potential as compared to marketed formulation.
Similar content being viewed by others
References
Morsi NM, Abdelbary GA, Ahmed MA. Silver sulfadiazine based cubosome hydrogels for topical treatment of burns: development and in vitro/in vivo characterization. Eur J Pharm Biopharm. 2013;86(2):178–89.
Ward RS, Saffle JR. Topical agents in burn and wound care. Phys Ther. 1995;75:526–38.
Robson MC, Mannari RJ, Smith PD, Payne WG. Maintenance of wound bacterial balance. Am J Surg. 1999;178:399–402.
Atiyeh BS, Costagliola M, Hayek SN, Dibo SA. Effect of silver on burn wound infection control and healing: review of the literature. Burns. 2007;33(2):139–48.
Bult A. Silver sulfadiazine and related antibacterial metal sulfanilamides: facts and fancy. Pharm Int. 1982;3:400–4.
Capelli CC, Wis K. Inventor; Biointerface Technologies, Inc., Madison, WI, assignee. Metal based antimicrobial coating. United States Patent 4933178.1990 June 12.
Venkataraman M, Nagarsenker M. Silver sulfadiazine nanosystems for burn therapy. AAPS PharmSciTech. 2012;14(1):254–64.
Capelli CCW, K. Inventor; Biointerface Technologies, Inc., Madison, WI, assignee. Metal based antimicrobial coating. United States Patent 4933178.1990 June 12.
Yalkowsky SH. Solubility and solubilization in aqueous media. New York: Oxford University Press; 1990.
Merisko-Liversidge E, Liversidge GG, Cooper ER. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 2003;18(2):113–20.
Gassmann P, List M, Schweitzer A, Sucker H. Hydrosols—alternatives for the parenteral application of poorly water-soluble drugs. Eur J Pharm Biopharm. 1994;40:64–72.
Mishra PR, Al Shaal L, Muller RH, Keck CM. Production and characterization of Hesperetin nanosuspensions for dermal delivery. Int J Pharm. 2009;371(1–2):182–9.
Kipp JE, Wong JCT, Doty MJ, et al. Inventor; Baxter International Inc., assignee. Microprecipitation method for preparing submicron suspensions. US Patent 6869617 B2. 2005 Mar 22.
Gao L, Zhang D, Chen M. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J Nanopart Res. 2008;10:845–62.
Xia D, Quan P, Piao H, Sun S, Yin Y, Cui F. Preparation of stable nitrendipine nanosuspensions using the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci. 2010;40(4):325–34.
Sigfridsson K, Forssen S, Hollander P, Skantze U, de Verdier J. A formulation comparison, using a solution and different nanosuspensions of a poorly soluble compound. Eur J Pharm Biopharm. 2007;67(2):540–7.
Muller MJ, Hollyoak MA, Moaveni Z, Brown TL, Herndon DN, Heggers JP. Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin. Burns. 2003;29(8):834–6.
Jia Y, Zhao G, Jia J. Preliminary evaluation: the effects of Aloe ferox Miller and Aloe arborescens Miller on wound healing. J Ethnopharmacol. 2008;120(2):181–9.
Heggers JP, Kucukcelebi A, Stabenau CJ, Ko F, Broemeling LD, Robson MC, et al. Wound healing effects of Aloe vera gel and other topical antimicrobial agents on rat skin. J Phytother Res. 1995;9:455–7.
Heggers JP, Pelley PP, Robson MC. Beneficial effects of aloe in wound healing. Phytother res. 1993;7:48–52.
Barkat MA, Ahmad J, Harshita, Ali R, Rahman MA, Kaleem S, et al. Formulation design of micronized silver sulfadiazine containing Aloe vera gel for wound healing. Curr Bioact Compd. 2016;12(2):63–8.
Subramanian S, Sathish KD, Arulselvan P. Wound healing potential of Aloe vera leaf gel studied in experimental rats. Asian J Biochem. 2006;1:178–85.
Tizard IR, Carpenter RH, McAnalley BH, Kemp MC. The biological activities of mannans and related complex carbohydrates. Mol Biother. 1989;1(6):290–6.
Hamid AAA, Soliman MF. Effect of topical Aloe vera on the process of healing of full-thickness skin burn: a histological and immunohistochemical study. J Histol Histopathol. 2015;2(1):3.
Rajasekaran S, Sivagnanam K, Ravi K, Subramanian S. Hypoglycemic effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats. J med Food. 2004;7(1):61–6.
Daburkar M, Lohar V, Rathore AS, Bhutada P, Tangadpaliwar S. An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer. J Pharm Bioallied Sci. 2014;6(3):205–12.
Singh A, Ahmad I, Akhter S, Jain GK, Iqbal Z, Talegaonkar S, et al. Nanocarrier based formulation of thymoquinone improves oral delivery: stability assessment, in vitro and in vivo studies. Colloids Surf B Biointerfaces. 2013;102:822–32.
Jodar KS, Balcao VM, Chaud MV, Tubino M, Yoshida VM, Oliveira JM Jr, et al. Development and characterization of a hydrogel containing silver sulfadiazine for antimicrobial topical applications. J Pharm Sci. 2015;104(7):2241–54.
Lee AR, Moon HK. Effect of topically applied silver sulfadiazine on fibroblast cell proliferation and biomechanical properties of the wound. Arch Pharm res. 2003;26:855–60.
Nascimento EG, Sampaio TB, Medeiros AC, Azevedo EP. Evaluation of chitosan gel with 1% silver sulfadiazine as an alternative for burn wound treatment in rats. Acta Cir Bras. 2009;24(6):460–5.
Govindarajan R, Vijayakumar M, Rao CV, Shirwaikar A, Mehrotra S, Pushpangadan P. Healing potential of Anogeissus latifolia for dermal wounds in rats. Acta Pharma. 2004;54(4):331–8.
Singer AJ, Clark RA. Cutaneous wound healing. N Engl J med. 1999;341:738–46.
Davis RH, Donato JJ, Hartman GM, Haas RC. Antiinflammatory and wound healing activity of a growth substance in Aloe vera. J am Podiatr med Assoc. 1994;84(2):77–81.
Boudreau M, Beland F. An evaluation of the biological and toxicological properties of Aloe barbadensis (Miller), Aloe vera. J Environ Sci Health. 2006;24(1):103–54.
Tamura N, Yoshida T, Miyaji K, Sugita-Konishi Y, Hattori M. Inhibition of infectious diseases by components from Aloe vera. Biosci Biotechnol Biochem. 2009;73(4):950–3.
Kuzuya H, Tamai I, Beppu H, Shimpo K, Chihara T. Determination of aloenin, barbaloin and isobarbaloin in aloe species by micellar electrokinetic chromatography. J Chromatogr B Biomed Sci Appl. 2001;752(1):91–7.
Sandri G, Bonferoni MC, Ferrari F, Rossi S, Aguzzi C, Mori M, et al. Montmorillonite-chitosan-silver sulfadiazine nanocomposites for topical treatment of chronic skin lesions: in vitro biocompatibility, antibacterial efficacy and gap closure cell motility properties. Carbohydr Polym. 2013;102:970–7.
Acknowledgements
The authors are thankful to Anju Drug chem, Indore, India, for gift samples of silver sulfadiazine. The first author acknowledges the University Grant Commission and Ministry of Social Justice, Government of India for providing Research fellowship.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Table S1
(DOCX 12 kb)
Rights and permissions
About this article
Cite this article
Barkat, M.A., Harshita, Ahmad, I. et al. Nanosuspension-Based Aloe vera Gel of Silver Sulfadiazine with Improved Wound Healing Activity. AAPS PharmSciTech 18, 3274–3285 (2017). https://doi.org/10.1208/s12249-017-0817-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-017-0817-y