Research Article Nanosuspension-Based Aloe vera Gel of Silver Sulfadiazine with Improved Wound Healing Activity Md Abul Barkat, 1,2 Harshita, 3 Iqbal Ahmad, 1 Raisuddin Ali, 4 Satya Prakash Singh, 2 Faheem Hyder Pottoo, 5 Sarwar Beg, 6 and Farhan Jalees Ahmad 1,7 Received 7 January 2017; accepted 23 May 2017 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. KEY WORDS: nanosuspension; nanoprecipitation; silver sulfadiazine; nanogel; drug release; histopathology. INTRODUCTION Burns are considered as one of the most severe forms of skin injuries. After injuries, the burn surface becomes susceptible to the bacterial attack because of the damage of the protective layers of skin and can cause sepsis and infections. The high bacterial load in the wound area can cause inhibition of growth factors that are able to slow down the progression of wound healing (1–3). The faster healing process and formation of epithelial cells to prevent infection are the key approaches used in burn management therapy. The topical application of drugs for treatment is important in case of major burns, thus helps in reducing the probability of wound sepsis (1). Among the topically used antibacterial agents, silver sulfadiazine (SSD) has established extensive acceptance to manage infections in second-degree burns (4). SSD is organo-silver salt with polymeric character, which comprises a blend of silver and sulfadiazine, where every silver ion is tetra-coordinated and encircled by three dissimilar deprotonated sulfa molecules attached with three dissimilar silver ions (5,6). SSD shows limited ef ficacy owing to its poor aqueous solubility and skin permeation property by virtue of its low lipophilicity characteristics (log p of 0.19). However, SSD is only freely soluble in 30% ammonia solution (7,8). Developing drug delivery systems of poorly soluble drug involves high degree of challenges for the formulation scientist, which requires thorough understanding of the material behavior for its appropriateness to design an effective drug delivery system (9). Nanosuspensions, in this regard, are highly suitable formula- tions to enhance the dissolution rate and therapeutic potential of poorly soluble drugs (7). Nanosuspension may contain crystalline or amorphous materials with a characteristic particle size between 100 and 1000 nm (10, 11). It can offer suitable way for oral and topical delivery of drugs due to small particle size and dissolution rate enhancement characteristics (12). Nanosuspensions can be Electronic supplementary material The online version of this article (doi:10.1208/s12249-017-0817-y) contains supplementary material, which is available to authorized users. 1 Nanomedicine Research Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India. 2 Department of Pharmaceutics, Faculty of Pharmacy, Integral University, Kursi Road, Lucknow, India. 3 Department of Pharmaceutics, College of Pharmacy, SGIT, Ghaziabad, UP, India. 4 College of Pharmacy, King Saud University, P.O. Box No. 2457, Riyadh, 11451, Kingdom of Saudi Arabia. 5 PG Department of Pharmaceutical Sciences, Faculty of Applied Sciences and Technology, University of Kashmir, Srinagar, J & K, India. 6 Jubilant Generics Limited, Noida, UP, India. 7 To whom correspondence should be addressed. (e-mail: farhan.ahmadjh@gmail.com) AAPS PharmSciTech ( # 2017) DOI: 10.1208/s12249-017-0817-y 1530-9932/17/0000-0001/0 # 2017 American Association of Pharmaceutical Scientists