Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

Co-delivery of Brinzolamide and Timolol from Micelles-laden Contact Lenses: In vitro and In Vivo Evaluation.

PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.

Association between periodontal diseases and chronic obstructive pulmonary disease: Evidence from sequential cross-sectional and prospective cohort studies based on UK Biobank.

AIM: To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large-scale prospective UK Biobank cohort. MATERIALS AND METHODS: Our approach comprised a cross-sectional study and a prospective cohort. Periodontal diseases were determined based on the participants' self-reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross-sectional study and the prospective cohort, respectively. RESULTS: The cross-sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015-1.059). The cohort study included 379,266 participants with a median follow-up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174-1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus. CONCLUSIONS: Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD.

Association between modifiable lifestyle pattern and periodontitis: a cross-sectional study based on NHANES.

BACKGROUND: Periodontitis can be avoided with a healthy lifestyle. However, studies have only looked at one lifestyle, ignoring the connection between lifestyle patterns and periodontitis. The purpose of this study was to look at the association between modifiable lifestyle patterns and periodontitis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey in 2009-2010 and 2011-2012. Smoke, drink, exercise, sleep duration, oral exams, and self-rated oral health were all lifestyle factors. The CDC/AAP classification/case definition was used to evaluate periodontitis. Drawing upon latent class analysis, distinct patterns of lifestyle were identified, with each participant exclusively affiliated with a single pattern. The association between lifestyle classes and periodontitis was then examined using ordinal logistic regression. RESULTS: 4686 (52%) of the total 9034 participants, with a mean age of 54.08, were women. Three lifestyle latent classes were found by fitting 2-10 models: "Class 1" (52%), " Class 2" (13%), and " Class 3" (35%). The "Class 1" displayed a prevalence of oral examination (75%), favorable self-rated oral health (92%), and engagement in physical activity (50%). The 'Class 2' exhibited the lowest alcohol consumption (64%) and smoking rates (73%) but the highest prevalence of physical inactivity (98%). The 'Class 3' showed a tendency for smoking (72%), alcohol consumption (78%), shorter sleep duration (50%), absence of oral examinations (75%), and suboptimal self-rated oral health (68%). The influencing variables for the latent classes of lifestyle were age, education, and poverty level. Periodontitis risk may rise by 24% for each additional unhealthy lifestyle practiced by participants (OR = 1.24, 95% CI: 1.18-1.31). The 'Class 3' (OR = 1.80, 95% CI: 1.52-2.13) had a greater risk of periodontitis compared to the 'Class 1'. CONCLUSIONS: Our analysis revealed that unhealthy lifestyle patterns are associated with periodontitis. These different lifestyle patterns need to be taken into account when developing public health interventions and clinical care.

Eco-Friendly One-Pot Supramolecular-Assembly of P-N Flame Retardant for Fire-Safe Epoxy Resin.

Flame retardant treatment of epoxy resins (EP) to reduce their flammability for extending their range of applications attracts considerable attention. However, the synthesis process of conventional flame retardants is complicated and involves organic hazardous solvents. Meanwhile, how to ensure both the flame-retardant and mechanical properties is a long-standing and actual difficult problem. In this work, a supramolecular flame retardant (named ATPFR) is facilely created by one-pot reaction, using cheap and accessible raw materials in an ecologically benign aqueous solvent. ATPFR is applied to improve the fire safety of EP. With only 5 wt% ATPFR addition, EP can reach the limiting oxygen index of 28.5% and the UL-94 V-0 rating with a significant "blow-out effect." The cone calorimetry test reveals that the EP thermoset with 5 wt% ATPFR has a 75.8% reduction in the peak heat release rate (p-HRR) and a 67.3% reduction in the peak smoke production rate (p-SPR), respectively, compared with the pure EP. Additionally, EP composites with the small amount of ATPFR exhibit a slight decrease and maintain good mechanical properties. Therefore, the facile synthesis and application of this supramolecular flame retardant provide a reliable way for the construction of polymer materials with environment-friendly and effective flame-retardant system.

Facile Ball Milling Preparation of Flame-Retardant Polymer Materials: An Overview.

To meet the growing needs of public safety and sustainable development, it is highly desirable to develop flame-retardant polymer materials using a facile and low-cost method. Although conventional solution chemical synthesis has proven to be an efficient way of developing flame retardants, it often requires organic solvents and a complicated separation process. In this review, we summarize the progress made in utilizing simple ball milling (an important type of mechanochemical approach) to fabricate flame retardants and flame-retardant polymer composites. To elaborate, we first present a basic introduction to ball milling, and its crushing, exfoliating, modifying, and reacting actions, as used in the development of high-performance flame retardants. Then, we report the mixing action of ball milling, as used in the preparation of flame-retardant polymer composites, especially in the formation of multifunctional segregated structures. Hopefully, this review will provide a reference for the study of developing flame-retardant polymer materials in a facile and feasible way.

Orthognathic Surgery in Invisalign Patients.

ABSTRACT: Orthodontic treatment combined with orthognathic surgery is frequently necessary to effectively manage patients suffering from severe craniofacial deformities. Brackets and wires are conventionally utilized for intraoperative splint stabilization in conventional orthognathic surgery, but such an approach is not applicable for patients undergoing treatment using clear aligners (the Invisalign system). The purpose of this article is to discuss the relative advantages, disadvantages, and challenges of using the Invisalign system when treating severe skeletal crossbite relative to cases treated using conventional braces. The case of this article described a 19-year-old male with skeletal class III crossbite undergoing planned Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO). For this patient, pre- and post-surgical orthodontics were conducted using an Invisalign system, with the interim and final splints being fixed to eight 8 mm mini-screws. Overall, this article reveals that the Invisalign system can be effectively employed for orthodontic treatment in combination with orthognathic surgery.

Vascularized Combined with Nonvascularized Fibula Flap for Mandibular Reconstruction: Preliminary Results of a Novel Technique.

BACKGROUND: Repair of long-span mandibular defects with vascularized free fibular grafts is now a routine procedure. Vertical discrepancy between a graft segment and the occlusal plane can be resolved through several options, including delayed onlay bone graft, iliac bone reconstruction, fibula distraction, and double-barrel fibula flap grafts. The present study (level of evidence: level IV, case series) introduces a new method for mandibular augmentation, wherein a vascularized fibular segment was used to simulate the superior alveolar ridge of the neomandible, whereas a nonvascularized fibular segment was used to reconstruct the inferior border. METHODS: Patients who underwent mandibular reconstruction with this technique between January 2014 and May 2017 were retrospectively reviewed for complications, vertical height, bone resorption rates, and crown to implant (C/I) ratios. RESULTS: The study included 10 patients. Flap loss occurred in 1 patient. A sufficiently long vascular pedicle could be maintained when the average fibular length was up to 15.3 cm to reconstruct long-span mandibular defects. Mean height of the neomandible at 2 weeks and 1 year after surgery was 34.1 and 29.4 mm, respectively. Mean resorption rates of vascularized and nonvascularized fibulas were 10.3% and 3.4%, respectively, at 1 year after surgery. Dental implants were placed in 4 patients with a mean C/I ratio of 1:1.15. CONCLUSION: The present method to reconstruct the alveolar ridge and basal portion of the mandible with vascularized and nonvascularized fibular flaps was safe and effective. It provided sufficient vertical height for lip support and implantation as well as adequate length for long-span mandibular reconstruction.

Comparison of static teeth exposure in different postures and its influencing factors of orthognathic surgery patients.

OBJECTIVES: This study aimed to explore the differences and influencing factors of static teeth exposure in different postures of orthognathic surgery patients. METHODS: A total of 148 patients were collected before or after orthognathic surgery. Photographs were taken in the upright and supine positions, and the static teeth exposure values were measured to compare whether the difference among different positions was statistically significant. The patients were classified in accordance with gender, presence or absence of orthodontic brackets, measurement time (preoperative or postoperative), and maxillary movement direction (forward or backward), and the difference of static teeth exposure was compared. The correlation between the difference of static teeth exposure and age was analyzed. RESULTS: The diffe-rence of static teeth exposure between the two positions was 0.99 mm±0.95 mm, which was statistically significant (P=0.000). A statistical difference in the difference of static exposure was observed between female and male (P<0.05). No statistical difference in the difference of static exposure was observed among orthodontic brackets, preoperative or postoperative time points, and maxillary movement direction. In addition, no significant correlation was found between the difference of static teeth exposure and age (r=-0.087, P=0.291). CONCLUSIONS: Compared with the upright position, the static exposure of teeth increased by approximately 0.99 mm in the supine position. The difference of static exposure under different postures was greater in males than in females. Furthermore, orthodontic bracket, maxillary surgery, maxillary movement direction, and age had no effect on the difference of static teeth exposure in different postures.

Solitary intraosseous neurofibroma in the mandible mimicking a cystic lesion: A case report and review of literature.

BACKGROUND: Neurofibromas are benign tumors of a neurogenic origin. If these tumors occur without any other signs of neurofibromatosis, they are classified as isolated neurofibromas. Neurofibromas in the oral cavity mostly occur within soft tissues, indicating that solitary intraosseous neurofibromas in the mandible are rare. Due to the absence of specific clinical manifestations, early diagnosis and treatment of these tumors are difficult to achieve. CASE SUMMARY: A 37-year-old female patient visited our hospital due to numbness and swelling of the gums in the right lower molar area that had persisted for half a month. The patient's overall condition and intraoral examination revealed no significant abnormalities. She was initially diagnosed with a cystic lesion in the right mandible. However, after a more thorough examination, the final pathological diagnosis was confirmed to be neurofibroma. Complete tumor resection and partial removal of the right inferior alveolar nerve were performed. As of writing this report, there have been no signs of tumor recurrence for nine months following the surgery. CONCLUSION: This case report discusses the key features that are useful for differentiating solitary intraosseous neurofibromas from other cystic lesions.

Rapamycin-loaded nanoparticles for inhibition of neointimal hyperplasia in experimental vein grafts.

BACKGROUND: Nanoparticles (NPs) possess several advantages as a carrier system for intracellular delivery of therapeutic agents. Rapamycin is an immunosuppressive agent which also exhibits marked antiproliferative properties. We investigated whether rapamycin-loaded NPs can reduce neointima formation of vein graft disease in a rat model. METHODS: Poly(lactic-co-glycolic acid) (PLGA) NPs-containing rapamycin was prepared using an oil/water solvent evaporation technique. The size and morphology of the NP were determined by dynamic light scattering methodology and electron microscopy. In vitro cytotoxicity of blank, rapamycin-loaded PLGA NPs was studied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Excised rat jugular vein was treated ex vivo with blank NPs, or rapamycin-loaded NPs, and then interposed back into the carotid artery position using a cuff technique. Grafts were harvested for 21 days and subjected to morphometric analysis as well as immunohistochemical analysis and Western blotting. RESULTS: Rapamycin was efficiently loaded in PLGA NPs with an encapsulation efficiency of 87.6%. The average diameter of NPs was 180.3 nm. The NPs-containing rapamycin at 1 ng/mL significantly inhibited vascular smooth muscular cells proliferation. Measurement of rapamycin levels in vein grafts showed that the concentration of rapamycin in vein grafts at 3 weeks after grafting was 0.9 ± 0.1 µg/g. In grafted veins without treatment, intima-media thickness was 300.4 ± 181.5 µm at 21 days after grafting, whereas veins treated with rapamycin-loaded NPs showed a reduction of intimal-media thickness of 150.2 ± 62.5 µm (p = 0.001). Cell proliferation was measured by proliferating cell nuclear antigen immunohistochemistry staining. As expected, proliferating cell nuclear antigen index declined from 83.4% ± 7.4% to 66.2% ± 4.5% in vein grafts after 3 weeks (p = 0.002). Platelet endothelial cell adhesion molecule (PECAM-1/CD31) staining was used to measure luminal endothelial coverage in grafts and indicated a high level of endothelialization at 21 days after grafting, with no significant effect of blank or rapamycin-loaded NPs group. Western blot analysis showed that treatment with rapamycin-loaded PLGA NPs markedly attenuated phosphorylation and activation of S6 kinase 1 phosphorylation and inactivation of 4E (eIF4E)-binding protein 1, both in vascular smooth muscular cells and vein grafts at 7 and 21 days after grafting. CONCLUSIONS: We conclude that sustained-release rapamycin from rapamycin-loaded NPs inhibits vein graft thickening without affecting the endothelial cells in rat carotid vein-to-artery interposition grafts; thus, this may be a promising therapy for the treatment of vein graft disease.

A nuclear targeted Dox-aptamer loaded liposome delivery platform for the circumvention of drug resistance in breast cancer.

The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs in the cytoplasm from the cell, is a major mechanism of MDR. Nuclear-targeted nanoparticle drug delivery system, which enables intranuclear release of anticancer drugs, is expected to address this challenge. In this study, based on nucleolin's active transport property to the nucleus and its affinity with aptamer, we developed a nuclear-targeted delivery system to circumvention of drug resistance in breast cancer (MCF-7/Adr). Dox·HCl inserted in the aptamer AS1411 (Ap-Dox) was encapsulated in the aqueous interior of liposome (Lip(Ap-Dox)). In vitro studies showed that after the Lip(Ap-Dox) diffusing into MCF-7/Adr cells, Ap-Dox complex bound with nucleolin strongly and eventually entered the cell nuclei. By using this drug delivery system, Dox·HCl can efficiently accumulated in the nuclei to effectively kill the cancer cells.

A Versatile Method to Enhance the Operational Current of Air-Stable Organic Gas Sensor for Monitoring of Breath Ammonia in Hemodialysis Patients.

Point-of-care (POC) application for monitoring of breath ammonia (BA) in hemodialysis (HD) patients has emerged as a promising noninvasive health monitoring approach. In this context, many organic gas sensors have been reported for BA detection. However, one of the major challenges for its integration with affordable household POC application is to achieve stable performance for accuracy and high operational current at low voltage for low-cost read-out circuitry. Herein, we exploited the stability of the Donor-Acceptor polymer on the cylindrical nanopore structure to realize the sensors with a high sensitivity and stability. Then, we proposed a double active layer (DL) strategy that exploits an ultrathin layer of Poly(3-hexylthiophene-2,5-diyl) (P3HT) to serve as a work function buffer to enhance the operational current. The DL sensor exhibits a sustainable enhanced operational current of microampere level and a stable sensing response even with the presence of P3HT layer. This effect is carefully examined with different aspects, including vertical composition profile of DL configuration, lifetime testing on different sensing layer, morphological analysis, and the versatility of the DL strategy. Finally, we utilize the DL sensor to conduct a tracing of BA concentration in two HD patients before and after HD, and correlate it with the blood urea nitrogen (BUN) levels. A good correlation coefficient of 0.96 is achieved. Moreover, the feasibility of DL sensor integrated into a low-cost circuitry was also verified. The results demonstrate the potential of this DL strategy to be used to integrate organic sensor for affordable household POC devices.

An unusual case of intraosseous mucoepidermoid carcinoma of the mandible: A case report and literature review.

RATIONALE: Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy. Ectopic MEC can occur in any part of the body, however, only 2% to 4% of MEC could be detected in the jaw, which is named intraosseous mucoepidermoid carcinoma (IMC). IMC is usually a low-grade carcinoma. Uni- or multilocular radiographic lesions should be differential diagnosed with ameloblastoma, odontogenic cysts, and glandular odontogenic cyst (GOC). Radical surgery may prefer for a favorable prognosis. Whereas IMC can recur long after the operation, a long-term follow-up system should be implemented. Owing to its rarity and controversial issues, we report a case report and review the literature to discuss its clinical features, treatments, radiological, and histological characteristics. PATIENT CONCERNS: The patient presented with a 2-month history of mild pain in the lower left posterior jaw without history of surgery or trauma to the mandible. DIAGNOSES: Routine postoperative pathology showed that the mass was consistent with a mandibular mucoepidermoid carcinoma. INTERVENTION: Radical surgery and digital mandibular reconstruction were performed. OUTCOME: Postoperative imaging showed that the height of the mandible and the symmetry of the mandible were satisfactory. The patient was also satisfied with her appearance. Follow-up has been established. LESSONS: Effective surgical treatment allows patients to have a favorable prognosis. A long-term follow-up system should be practiced, because local recurrences and regional metastasis could happen even after decades.

Expression levels of B7-H3 and TLT-2 in human oral squamous cell carcinoma.

The aim of the present study was to investigate the role of immune regulatory molecules B7-H3 [also known as cluster of differentiation 276] and triggering receptor expressed on myeloid cell-like transcript-2 (TLT-2) in patients with oral squamous cell carcinoma (OSCC). Human OSCC samples were obtained from 76 patients (female, 32; male, 44; age range, 23-81 years; median age, 50.9 years) that underwent resection for OSCC at Peking University Shenzhen Hospital (Shenzhen, China) between 2007 and 2010. In addition, control oral mucosal samples were obtained from 76 healthy individuals (female, 36; male, 40; age range, 21-62 years; median age, 45.3 years) during wisdom tooth extraction. Protein and gene expression levels of B7-H3 and TLT-2 were determined by immunohistochemical analysis and reverse transcription-polymerase chain reaction (RT-PCR). In the healthy oral mucosa samples, B7-H3 expression was identified to be weak, while the expression of TLT-2 was only detected sporadically in the cell membrane and cytoplasm. By contrast, the two regulatory molecules were widely expressed in the aforementioned localizations in human OSCC specimens upon immunohistochemical examination. Furthermore, quantitative RT-PCR confirmed the presence of significantly higher B7-H3 and TLT-2 expression levels in OSCC specimens compared with the oral mucosa of healthy individuals. The significantly higher expression levels of B7-H3 and TLT-2 in human OSCC specimens may indicate an inhibitory role of these molecules in the antitumoral immune response. To investigate interactions between these two molecules and individual antitumoral immune response in OSCC patients, prospective clinical studies with an adequate sample size are required.

Basaloid squamous cell carcinoma of the maxillary gingiva: A case report and review of the literature.

Basaloid squamous cell carcinoma (BSCC) is a rare, but distinct histologic variant of squamous cell carcinoma in the head and neck region. It is considered to have a poor prognosis due to its aggressive behavior and tendency to metastasize. The usual sites of BSCC are the floor of the mouth, hypopharynx and base of the tongue, and according to the English-language literature its presentation in the gingiva is somewhat uncommon. In the current report, the unusual case of a 40-year-old male is presented; the patient exhibited a painless irregular mass in the maxillary gingiva, which infiltrated the maxillary sinus, as observed by computed tomography. Hematoxylin and eosin-stained sections revealed a diagnosis of BSCC with typical central necrosis in the cancer nests, which contained basaloid and squamous cells. Immunohistochemistry revealed that p63 was weakly positive, high molecular weight cytokeratin (CK) was focally positive, and S-100, CK7, CK14 and vimentin were negative. It must be noted that histopathology results may be incorrectly interpreted as adenoid cystic carcinoma, undifferentiated carcinoma and basal cell adenocarcinoma.