Research Article Effective Topical Delivery of H-AgNPs for Eradication of Klebsiella pneumoniae–Induced Burn Wound Infection Sanjay Chhibber, 1,5 Vijay Singh Gondil, 1 Love Singla, 1 Munish Kumar, 2 Tanya Chhibber, 3 Gajanand Sharma, 3 Rohit Kumar Sharma, 2 Nishima Wangoo, 4 and Om Prakash Katare 3 Received 6 November 2018; accepted 22 February 2019 Abstract. The aim of the present study was to explore the therapeutic efficacy of microemulsion-based delivery of histidine-capped silver nanoparticles in eradicating Klebsi- ella pneumoniae–induced burn wound infection. The developed microemulsion was characterized on the basis of differential light scattering, phase separation, refractive index, and specific conductance. Emulgel was prepared and characterized on the basis of thixotropy, texture, differential scanning calorimetry, and release kinetics. Emulgel was further evaluated in skin irritation and in vivo studies, namely full-thickness K. pneumoniae–induced burn wound infection treatment via topical route. Efficacy of treatment was evaluated in terms of bacterial load, histopathology, wound contraction, and other infection markers. The developed emulgel provided significant in vivo antibacterial activity of histidine-capped silver nanoparticle preparations via topical route and resulted in reduction in bacterial load, wound contraction, and enhanced skin healing as well as decrement of inflammatory markers such as malondialdehyde, myeloperoxidase, and reactive nitrogen intermediate compared to untreated animals. The present study encourages the further employment of histidine-capped silver nanoparticles along with microemulsion-based drug delivery system in combating antibiotic-resistant topical infections. KEY WORDS: silver nanoparticles; topical delivery; antibiotic resistance. INTRODUCTION Burn wound healing and skin tissue regeneration remain two of the most important challenges facing the mankind as bacterial infections are a major cause of worry in burn patients (1). Klebsiella pneumoniae is known to be a major colonizer of burn wound along with Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli (2–4). Its rapid spreading ability in hospital environment and antibiotic resistance have resulted in high morbidity and mortality in recent years (5,6). Due to inevitable spread of multidrug-resistant bacteria and inability to develop new antibiotics, there is an immense need of exploring new remedial resources such as phage therapy (7,8), enzybiotics (9,10), antibacterial nanoparticles (11–13), phytochemicals (14,15), pigments (16,17), and other antimicrobial products. The antibacterial nature of silver is a well-established concept and silver salts as well as their derivatives are used as antibacterial additive in a number of products (18–20). Silver nanoparticles showed a higher rate of antimicrobial activity than silver salts, which is correlated with their size, geometry, surface modifications, and method of preparation (21, 22). Silver nanoparticles exhibit their antimicrobial potential by a number of mechanisms, such as free radical formation that results in membrane disruption (23, 24), DNA degradation (25), and inhibition of DNA replication (26, 27). Chemically synthesized silver nanoparticles were known for their antibacterial and antibiofilm potential (11), but recently amino acid–capped silver nanoparticles have been exploited for their antibacterial as well as antibiofilm activity. In our earlier study, histidine-capped silver nanoparticles (H-AgNPs) showed antibac- terial activity against planktonic as well as adherent biofilm cells, and present themselves as a potential candidate for further in vivo studies (25). Application of therapeutic agents through topical route has shown a number of intricacies such as localized delivery and containment of nanoparticles to site of infection. To conquer current problems, carrier vehicles can be used to deliver the nanoparticles at site of infection topically. Administration of Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-019-1350-y) contains supplementary material, which is available to authorized users. 1 Department of Microbiology, Basic Medical Sciences, Panjab University, Chandigarh, India. 2 Department of Chemistry, Panjab University, Chandigarh, India. 3 Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. 4 Department of Applied Sciences, University Institute of Engineer- ing and Technology, Panjab University, Chandigarh, India. 5 To whom correspondence should be addressed. (e–mail: sanjaychhibber8@gmail.com) AAPS PharmSciTech (2019) 20:169 DOI: 10.1208/s12249-019-1350-y 1530-9932/19/0000-0001/0 # 2019 American Association of Pharmaceutical Scientists