Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV؉ individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent.

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The predictability of multivariate calibration models, calculated with offline near-infrared spectroscopy (NIRS), assessing impact of magnesium stearate (MgSt) fraction, blending time, and compression force on the tablet breaking force (TBF) of SPRESS B820 was statistically compared. Tablets of lubricated SPRESS B820 were prepared by varying lubrication and compression conditions using 2 full factorial design. Tablets were scanned in reflection mode on a benchtop NIRS. A qualitative principal component analysis and quantitative principal component regression (PCR) and partial least square (PLS) regression relationship between lubricant concentration, blending time, compression force, preprocessed NIR spectra, and measured TBF was calculated with calibration data set. The predictability of calibration models was validated with independent data set. Expected qualitative correlations between MgSt blending time and TBF and a nonlinear relationship between MgSt fraction and TBF were observed. Predictability of PLS comprehensive (0.25%-1% w/w MgSt) model was significantly different from individual 0.25%, 0.5%, and 1.0% w/w MgSt PLS models. In addition, PLS calibration models' predictability was different from PCR calibration models. Thus, added lubrication fraction and adopted multivariate methodology should be selected carefully during the calibration and validation stages as it may have a significant impact on the predictability of the developed models.