Atomized paclitaxel liposome inhalation treatment of bleomycin-induced pulmonary fibrosis in rats.

We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-ß1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-ß1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection.

[A two-dimensional photographic and three-dimensional digital dental model comparative analysis in maxillary anterior teeth].

Objective: To assess the accuracy of two-dimensional (2D) photographs in measuring esthetic parameters of the maxillary anterior teeth by comparing them with measurements obtained from three-dimensional (3D) dental models. Methods: A total of one hundred volunteers (49 males, 51 females, aged 18-23 years) were recruited from School and Hospital of Stomatology, Wuhan University from January to February 2024. 3D digital models of their dentitions were obtained using an intraoral scanner, and standardized frontal 2D intraoral photographs were captured with a digital camera. The lengths, widths and width/length ratio of the bilateral incisors, lateral incisors and canines were measured on both the 3D digital models and the 2D intraoral photographs. The width ratios of adjacent maxillary anterior were also calculated on the 2D intraoral photographs and the frontal view of 3D digital models. Results: The widths of lateral incisors [(5.85±0.60) mm] and canines [(4.73±0.71) mm] and the lengths of canines [(8.72±0.96) mm] in the 2D intraoral photographs were significantly lower than those in 3D digital models [(6.65±0.59), (7.76±0.60), (8.90±0.86) mm] (t=-18.24, P<0.001; t=-54.43, P<0.001; t=-4.40, P<0.001), while there were no significant differences in the lengths and widths of the other teeth (P>0.05). The width/length ratios measured from the 2D intraoral photographs for the lateral incisors and canines (0.74±0.08, 0.55±0.08) were significantly lower than those measured in the 3D digital models (0.84±0.09, 0.88±0.09) (t=-19.68, P<0.001; t=-50.21, P<0.001), and the width/length ratio of the central incisors showed no significant difference between the two groups (P>0.05). The width ratios of canines/lateral incisors and lateral incisors/central incisors measured on the 2D intraoral photographs (0.72±0.06, 0.85±0.11) were significantly smaller than those measured in the frontal view of 3D digital models (0.75±0.06, 0.89±0.11) (t=-9.31, P<0.001; t=-6.58, P<0.001). Conclusions: There is a difference between 2D and 3D measurement results of teeth in the esthetic area and the magnitude of the difference varies with their position in the dental arch. When analyzing the measurement of the anterior teeth, it is necessary to choose the appropriate method according to the target tooth position.

Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin.

Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and it was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99±7.96µg/cm2/h) compared to the xanthan gum (1.16±0.14µg/cm2/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95±28.63µg/cm2/h) compared to the equivalent xanthan gum system (14.19±2.27µg/cm2/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather, they were a consequence of the dehydration mediated diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.

Investigating the influence of drug aggregation on the percutaneous penetration rate of tetracaine when applying low doses of the agent topically to the skin.

Understanding the molecular aggregation of therapeutic agents is particularly important when applying low doses of a drug to the surface of the skin. The aim of this study was to understand how the concentration of a drug influenced its molecular aggregation and its subsequent percutaneous penetration after topical application. A model drug tetracaine was shown to form a series of different aggregates across the µM (fluorescence spectroscopy) to mM (light scattering analysis) concentration range. The aggregate formation process was sensitive to the pH of the vehicle in which the drug was dissolved (pH 4, critical aggregation concentration (CAC) - 11 µM; pH 8, CAC - 7 µM) and it appeared to have an impact upon the drug's percutaneous penetration. At pH 4, increasing the concentration of the drug in the donor solution decreased the skin permeability coefficient (Kp) of tetracaine (13.7 ± 4.3 × 10(-3)cm/h to 0.06 ± 0.02 × 10(-3)cm/h), whilst at pH 8, it increased the Kp (29.9 ± 9.9 × 10(-3)cm/h to 75.1 ± 41.7 × 10(-3)cm/h). These data trends were reproduced in a silicone membrane and this supported the notion that the more polar aggregates formed at pH 4 acted to decrease the proportion of species available to pass through the skin, whilst the more hydrophobic aggregates formed in pH 8 increased the membrane diffusing species.