Physico-chemistry and Cytotoxicity of Tenofovir-Loaded Acid Phosphatase-Responsive Chitosan Nanoparticles.

This study assesses the in vitro release of tenofovir (TFV)-loaded triphosphate (TPP) cross-linked chitosan nanoparticles (NPs) catalyzed by human prostatic acid phosphatase (hPAP) for 24 h. The physico-chemical characterization of the NPs included particle mean diameter (PMD), zeta potential (ζ), percent drug encapsulation efficiency (% EE), Fourier transform infra-red (FTIR) spectroscopy, powder X-ray diffractometry analysis (PXRD), and drug release kinetics. The first-order rate constant (k) and activation energy (Ea) of the cross-link (TPP) are determined by the integrated rate law and Arrhenius's equations. The hPAP Michaelis-Menten constant (Km) is determined by the Lineweaver-Burk's equation. The NP's safety profile is evaluated on vaginal epithelial cells (VK2/E6E7). The lyophilized drug-loaded NPs' PMD, ζ, and PDI are 149.97 nm, 4.4 mV, and 0.3, respectively. The % EE after lyophilization is 93.7 ± 4.4%. These NPs released drug at faster rate (63% of TFV within 6 h) under the enzyme's influence. The similarity and difference factors of drug release profiles (absence vs presence of hPAP) are 56.5 and 40.3, respectively. The hPAP's Km value of 0.019 mM suggests it has a good affinity for TPP at physiological pH ~ 7.4. The enhanced hydrolysis of TPP or degradation of chitosan NPs is fundamentally due to a decrease of TPP's activation energy by hPAP. In fact, the Ea value is 22.50 ± 3.06 kJ/mol or 16.33 ± 0.62 kJ/mol in the absence or presence of hPAP, respectively. The NPs are non-cytotoxic to the treated vaginal cell line. These hPAP-responsive NPs are promising topical nanomicrobicides for HIV/AIDS prevention.

Prevalence of Hypertension in Homeless Adults: An Interprofessional Education Community-Based Health Fairs Cross-Sectional Study in Urban Long Beach, California.

INTRODUCTION: Hypertension (SBP/DBP > 130/80 mmHg) is a leading risk factor for cardiovascular disease worldwide. AIM: To determine the prevalence of hypertension in a homeless community during an interprofessional education (IPE)-based health fair. METHODS: Homeless participants were recruited between August 2019-September 2019. Faculty, nursing, and pharmacist students, educated 477 participants, aged 18-80 years, on the risk factors associated with untreated hypertension. Then, participants self-completed the consented demographic survey questionnaire. Finally, the sitting blood pressure (BP) was recorded three times based on a standardized procedure, using Omron BPN monitor with cuff. RESULTS: Seven pharmacy students, nine nursing students, two registered nurses, five registered pharmacists, and two medical doctors collaboratively provided health education to the homeless community and screened their sitting BP. 390/477 (81.8%) of participants satisfied the inclusion criteria. Participants (54.7%) of the reported education level was at the high School level or less. More than the half of the participants (average age of 51 ± 13 years) had hypertension (median SBP/DBP ≥ 130/82.7 mmHg), respectively. The prevalence of hypertension for the overall cohort was 61.52% (95% CI, 56.59-66.35). Age (p value = 0.000) was significantly associated with hypertension based on the binary logistic analysis. CONCLUSION: This study demonstrated a high prevalence of hypertension in the homeless community in Long Beach, California with high risk of cardio-vascular events or strokes. This works sheds new light on an issue of major public health significance and points to the need for fostering IPE community-based health fairs intervention program for the US homeless population.

Engineering fast dissolving sodium acetate mediated crystalline solid dispersion of docetaxel.

It is hypothesized that a novel crystalline solid dispersion (CSD) of docetaxel (C-DXT) can be engineered by dispersing native docetaxel (DXT, a BCS class II drug) in sodium acetate crystal (SA). DXT is dissolved in glacial acetic/SA solution and freeze-dried. The resulting C-DXT is characterized by differential scanning calorimetry (DSC), powder X-ray analysis (PXRD), LC-MS/MS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Quartz crystal microbalance with dissipation monitoring (QCM-D) and dynamic light scattering (DLS). Its cytotoxicity on model cancerous (MCF-7, MDA-MB-468) and normal breast cells (MCF-10A) is assessed by MTS assay. SEM/TEM data and the absence of the characteristics peaks of DXT on the DSC curve (at 193.4 °C) and the XRD scan (at 2θ = 15.31 °C and 23.04 °C) confirm the presence of C-DXT in SA. The LC-MS/MS data indicates the chemical stability of DXT. The yield and C-DXT loading are 95.2% and 6.52% w/w, respectively. The C-DXT rapidly forms an aqueous non-rigid nanosuspension with a faster drug dissolution rate compared to native DXT. Unlike, control Tween 80/ethanol, SA is noncytotoxic to normal cells. However, C-DXT's cytotoxicity is time and dose dependent for all diseased cells. This unique CSD process might be applicable to other hydrophobic bioactive agents to enhance their safety and efficacy.

Image-guided Removal of Interproximal Lesions with a CO2 Laser.

Recent studies have shown that near-IR (NIR) imaging methods such as NIR reflectance can be used to image lesions on proximal surfaces, and optical coherence tomography (OCT) can be used to measure the depth of those lesions below the tooth surface. These imaging modalities can be used to acquire high contrast images of demineralized tooth surfaces, and 2-D and 3-D images can be extracted from this data. At NIR wavelengths longer than 1200-nm, there is no interference from stains and the contrast is only due to the increased light scattering of the demineralization. Previous studies have shown that image-guided laser ablation can be used to remove occlusal lesions, but its use for the removal of subsurface lesions on proximal surfaces has not been investigated. The objective of this study is to demonstrate that simultaneously scanned NIR and CO2 lasers can be used to selectively remove natural and artificial interproximal caries lesions with minimal damage to sound tooth structure. In this study, images of simulated and natural interproximal lesions on extracted teeth were imaged using a digital microscope, a scanned 1460-nm superluminescent laser diode with an InGaAs detector and a cross polarization OCT system operating at 1300-nm. The lesions were subsequently removed with a CO2 laser operating at 9.3-µm and the dental handpiece and the volume of sound tissue removed was compared.

Sodium Acetate Coated Tenofovir-Loaded Chitosan Nanoparticles for Improved Physico-Chemical Properties.

PURPOSE: It is hypothesized that sodium acetate (SA) can be used for in situ coating of drug loaded chitosan NPs for improved physico-chemical properties. METHODS: Tenofovir (TFV) is used as a model drug. Uncoated chitosan NPs are prepared by ionic gelation. SA is generated in situ from half neutralization of acetic acid with sodium hydroxide, and coats chitosan NPs during freeze-drying. The NPs' physico-chemical properties [e.g., particle mean diameters (PMD) zeta potential (ζ), EE%, drug release profile, morphology] are characterized by dynamic light scattering, spectrophotometry, Korsmeyer-Peppas model, transmission electron microscopy (TEM), respectively. Melting point (MP), non-aqueous titration, Fourier transform infrared (FTIR) analysis, and powder X-ray diffractometry (XRD) pattern evaluate the SA coated chitosan NPs. The NPs' cytotoxicity on macrophages Raw 264.7 is assessed by neutral red, resazurin, nitrite oxide (NO) and cytokines assays. RESULTS: Collectively, FTIR, ζ, XRD, MP, and TEM data confirm that SA coats chitosan NPs. The PMD range is 136-348 nm (uncoated) and 171-379 nm (coated NPs). The ζ values range is +24.3-28.5 mV (uncoated) and 0.1-3.1 mV (coated NPs). The EE% ranges from 5.5 to 11.7% (uncoated NPs) and increased up to 86.3-92.7%(8-17-fold) after coating. The SA also prevents NPs aggregation during the freeze-drying and aqueous dispersion. The core-shell NPs exhibited a sustain release of TFV following anomalous transport mechanism (R(2) ~ 0.99). The coated NPs are non-cytotoxic (cell viability ~100%) and without any proinflammatory response. CONCLUSIONS: This SA coating chitosan NPs mechanism may be useful for (i) efficient encapsulation, (ii) stabilizing colloidal dispersions, (iii) controlling the release and solubility of bioactive agents.

Prevalence of Enamel Markings on Third Molars.

The purpose of this study was to measure the prevalence of enamel markings in routinely extracted third molars. One hundred donated third molars were examined. All had some marking(s). Caries was almost universal; white snowcapping of cusps and ridges was extremely common; pit and valley defects were very common; spots and bands were very common, most were white; horizontal grooves were common; linear enamel hypoplasia, considered to be a true developmental defect, was rare.

Optimal Concentration of 2,2,2-Trichloroacetic Acid for Protein Precipitation Based on Response Surface Methodology.

For low protein concentrations containing biological samples (in proteomics) and for non proteinaceous compound assays (in bioanalysis), there is a critical need for a simple, fast, and cost-effective protein enrichment or precipitation method. However, 2,2,2-trichloroacetic acid (TCA) is traditionally used for protein precipitation at ineffective concentrations for very low protein containing samples. It is hypothesized that response surface methodology, can be used to systematically identify the optimal TCA concentration for protein precipitation in a wider concentration range. To test this hypothesis, a central composite design is used to assess the effects of two factors (X1 = volume of aqueous solution of protein, and X2 = volume of TCA solution 6.1N) on the optical absorbance of the supernatant (Y1), and the percentage of protein precipitated (Y2). Using either bovine serum albumin (BSA) as a model protein or human urine (with 20 ppm protein content), 4% w/v (a saddle point) is the optimal concentration of the TCA solution for protein precipitation that is visualized by SDS-PAGE analysis. At this optimal concentration, the Y2-values range from 76.26 to 92.67% w/w for 0.016 to 2 mg/mL of BSA solution. It is also useful for protein enrichment and xenobiotic analysis in protein-free supernatant as applied to tenofovir (a model HIV microbicide). In these conditions, the limit of detection and limit of quantitation of tenofovir are respectively 0.0014 mg/mL and 0.0042 mg/mL. This optimal concentration of TCA provides optimal condition for protein purification and analysis of any xenobiotic compound like tenofovir.