Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge.

BACKGROUND: Cilomilast is a phosphodiesterase 4 (PDE4) inhibitor for treating inflammatory lung diseases. This agent has a narrow therapeutic index with significant adverse effects on the nervous system. This study was conducted to entrap cilomilast into PEGylated phosphatidylcholine-rich niosomes (phosphatiosomes) to improve pulmonary delivery via the strong affinity to pulmonary surfactant film. Neutrophils were used as a cell model to test the anti-inflammatory activity of phosphatiosomes. In an in vivo approach, mice were given lipopolysaccharide to produce acute lung injury. The surface charge in phosphatiosomes that influenced the anti-inflammatory potency is discussed in this study. RESULTS: The average diameter of the phosphatiosomes was about 100 nm. The zeta potential of anionic and cationic nanovesicles was - 35 and 32 mV, respectively. Cilomilast in both its free and nanocapsulated forms inhibited superoxide anion production but not elastase release in activated neutrophils. Cationic phosphatiosomes mitigated calcium mobilization far more effectively than the free drug. In vivo biodistribution evaluated by organ imaging demonstrated a 2-fold ameliorated lung uptake after dye encapsulation into the phosphatiosomes. The lung/brain distribution ratio increased from 3 to 11 after nanocarrier loading. The intravenous nanocarriers deactivated the neutrophils in ALI, resulting in the elimination of hemorrhage and alveolar wall damage. Only cationic phosphatiosomes could significantly suppress IL-1ß and TNF-α in the inflamed lung tissue. CONCLUSIONS: These results suggest that phosphatiosomes should further be investigated as a potential nanocarrier for the treatment of pulmonary inflammation.

Proteinase K/Retinoic Acid-Loaded Cationic Liposomes as Multifunctional Anti-Acne Therapy to Disorganize Biofilm and Regulate Keratinocyte Proliferation.

Background: Simultaneous anti-Cutibacterium acnes and anti-inflammatory actions are highly beneficial in treating acne vulgaris. In this study, we present novel anti-acne nanovesicles based on liposomes loaded with proteinase K (PK), retinoic acid (RA), and soyaethyl morpholinium ethosulfate (SME) to achieve an effective and safe treatment. Materials and Methods: This study examined in vitro planktonic and biofilm C. acnes elimination, as well as the keratinocyte proliferation suppression by liposomes. The multifunctional liposomes for treating C. acnes in mice were also evaluated. Results: We acquired multifunctional liposomes with a size of 71 nm and zeta potential of 31 mV. The antimicrobial activity of SME was enhanced after liposomal encapsulation according to the reduction of minimum bactericidal concentration (MBC) by 6-fold. The multifunctional liposomes exhibited a synergistically inhibitory effect on biofilm C. acnes colonization compared with the liposomes containing PK or those containing SME individually. The adhesive bacterial colony in the microplate was lessened by 62% after multifunctional liposome intervention. All liposomal formulations tested here demonstrated no cytotoxicity against the normal keratinocytes but inhibited C. acnes-stimulated cell hyperproliferation. The in vitro scratch assay indicated that the liposomal RA-but not free RA-restrained keratinocyte migration. The animal study showed that free RA combined with SME and multifunctional nanovesicles had a similar effect on diminishing C. acnes colonies in the skin. On the other hand, liposomes exhibited superior performance in recovering the impaired skin barrier function than the free control. We also found that RA-loaded nanovesicles had greater skin tolerability than free RA. Conclusion: The cationic liposomes containing dual PK and RA represented a potential treatment to arrest bacterial infection and associated inflammation in acne.

Effectiveness of Virtual Reality-Based Training on Oral Healthcare for Disabled Elderly Persons: A Randomized Controlled Trial.

(1) Background: Virtual reality (VR) technology is a widely used training tool in medical education. The present study aimed to evaluate the effectiveness of VR training of oral hygiene students on providing oral healthcare to disabled elderly persons. (2) Methods: A randomized controlled trial was conducted. In 2021, oral hygiene students were randomly assigned to a VR experimental group (EG; n = 11) and a control group (CG; n = 12). The EG received two-hour, thrice-repeated VR-based training interventions at 2-week, 4-week, and 6-week follow-ups. The CG received no VR-based interventions. Data were collected using a self-administered questionnaire before and immediately after each intervention. We performed generalized estimating equations to compare the responses. (3) Results: The EG exhibited a more significant improvement in oral care-related knowledge, attitude, self-efficacy, and intention at the 6-week follow-up than the CG. The students' intention to assist the elderly in using interdental brushes (ß = 0.91), with soft tissue cleaning (ß = 0.53), and with oral desensitization (ß = 0.53), and to have regular dental visits (ß = 0.61) improved significantly at the 6-week follow-up. (4) Conclusions: VR training positively affected students' knowledge, attitude, self-efficacy, and intentions on providing oral healthcare to disabled elderly persons.

Holistic care for obstructive sleep apnea (OSA) with an emphasis on restoring nasal breathing: A review and perspective.

Obstructive sleep apnea (OSA) is characterized by partial or complete airway blockage during sleep. Nocturnal nasal obstruction usually leads to mouth breathing while sleeping, which worsens sleep apnea by aggravating tongue base and lateral pharyngeal wall collapse. The pathogenesis of OSA is multifactorial, and the precipitating factors vary significantly among individuals. Although continuous positive airway pressure (CPAP) is considered the first-line therapy for OSA, its adherence rate remains a challenge. Oral appliances are more suitable for simple snorers or patients with mild OSA. Maxillomandibular advancement (MMA) is highly effective for treating those with mandibular retrognathia and moderate-to-severe OSA. Intrapharyngeal surgeries yield favorable outcomes in patients with large tonsils and low tongue resting position (Friedman Stage I); however, their efficacy declines with time. Each therapy has its own strength and weakness; thus, the principle of multimodality treatment should be adopted. Nasal surgery plays an indispensable role in the holistic care for OSA. In addition to alleviating nasal congestion, nasal surgery significantly reduces snoring intensity and daytime sleepiness, which improves the quality of life of patients with OSA. Although it significantly reduces the respiratory disturbance index, its effect on the apnea-hypopnea index remains controversial. A combination of nasal surgery and multilevel pharyngeal surgery may result in better prognosis. Nasal surgery can significantly reduce the therapeutic pressure and improve the CPAP compliance of patients undergoing CPAP therapy. In conclusion, multimodality treatment and holistic care for OSA should involve nasal surgery for optimizing treatment outcomes.

A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity.

An often-proposed tissue engineering design hypothesis is that the scaffold should provide a biomimetic mechanical environment for initial function and appropriate remodeling of regenerating tissue while concurrently providing sufficient porosity for cell migration and cell/gene delivery. To provide a systematic study of this hypothesis, the ability to precisely design and manufacture biomaterial scaffolds is needed. Traditional methods for scaffold design and fabrication cannot provide the control over scaffold architecture design to achieve specified properties within fixed limits on porosity. The purpose of this paper was to develop a general design optimization scheme for 3D internal scaffold architecture to match desired elastic properties and porosity simultaneously, by introducing the homogenization-based topology optimization algorithm (also known as general layout optimization). With an initial target for bone tissue engineering, we demonstrate that the method can produce highly porous structures that match human trabecular bone anisotropic stiffness using accepted biomaterials. In addition, we show that anisotropic bone stiffness may be matched with scaffolds of widely different porosity. Finally, we also demonstrate that prototypes of the designed structures can be fabricated using solid free-form fabrication (SFF) techniques.