Research Article Stimuli Responsive In Situ Gelling Systems Loaded with PLGA Nanoparticles of Moxifloxacin Hydrochloride for Effective Treatment of Periodontitis Sarwar Beg, 1,2 Shashi Dhiman, 1 Teenu Sharma, 1 Ashish Jain, 3 Rakesh Kumar Sharma, 4 Atul Jain, 5 and Bhupinder Singh 1,5,6 Received 15 August 2019; accepted 17 December 2019; published online 22 January 2020 Abstract. The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1 week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1 week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3 weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment. KEY WORDS: quality by design; periodontitis; nanoparticles; thermo-responsive gels; γ-scintigraphy. INTRODUCTION Periodontitis encompasses severe infection caused by Gram-negative anaerobic bacterial species, especially by Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which primarily affect the periodon- tium, leading eventually to accumulation of plaque in subgingival cavity of the periodontal pocket. This causes inflammation of gums and associated structures including periodontal ligaments, alveolar bone and dental cementum (1,2). Numerous drug delivery systems like dental solutions, gels, films, inserts and implants have been explored for the treatment and management of periodontitis by site-specific delivery of antimicrobial therapeutics for reducing the growth of microorganisms in the periodontal pocket (3,4). However, major hiccups comprise the need for frequent drug adminis- tration at periodic intervals for multiple times, poor retention of drug in the periodontal pockets for the desirable extended time periods, resulting eventually in the reduced treatment efficacy and patient acceptance (5,6). Moxifloxacin hydrochloride (MOX), chemically known as 8-methoxy-quinolone, has been reported to possess broad spectrum antimicrobial action on wide range of pathogens. It shows therapeutic action by inhibiting the DNA- topoisomerase II and IV enzymes, which are necessary to separate the bacterial DNA, thereby inhibiting the replication of cells (7,8). Literature reports have documented its efficacy against P. gingivalis and A. actinomycetemcomitans, the organisms primarily responsible for causing periodontitis (9). Among the several drugs available in the quinolone series, MOX was selected owing to its low MIC against P. gingivalis and A. actinomycetemcomitans, which is found to be effective Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-019-1613-7) contains supplementary material, which is available to authorized users. 1 University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, 160014, India. 2 Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India. 3 Dr. H.S. Judge Institute of Dental Science, Panjab University, Chandigarh, 160014, India. 4 Saveetha Institute of Medical and Technical Sciences (Deemed to be University), Chennai, 602105, India. 5 UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, 160014, India. 6 To whom correspondence should be addressed. (e–mail: bsbhoop@yahoo.com; bsbhoop@pu.ac.in) AAPS PharmSciTech (2020) 21: 76 DOI: 10.1208/s12249-019-1613-7 1530-9932/20/0300-0001/0 # 2020 American Association of Pharmaceutical Scientists