Cholesterol-conjugated poly(D,L-lactide)-based micelles as a nanocarrier system for effective delivery of curcumin in cancer therapy

Polymeric micelles have been widely explored preclinically as suitable delivery systems for poorly soluble chemotherapeutic drugs in cancer therapy. The present study reported the development of cholesterol (Ch)-conjugated poly(D,L-Lactide) (PLA)-based polymeric micelles (mPEG–PLA-Ch) for effective encapsulation and delivery of curcumin (CUR) at the tumor site. Cholesterol conjugation dramatically affected the particle size and improved drug loading (DL) and encapsulation efficiency (EE). mPEG–PLA-Ch-CUR showed bigger hydrodynamic diameter (104.6?±?2.1?nm, and 169.3?±?1.52?nm for mPEG–PLA and mPEG–PLA-Ch, respectively) due to increased size of the hydrophobic core. The newly developed polymer exhibited low critical micelles concentration (CMC) (25?μg/mL) which is close to lipid-based polymer, PEG-phosphatidyl ethanolamine (12.5?μg/mL) compared to mPEG–PLA (50?μg/mL). mPEG–PLA-Ch micelles exhibited relatively higher EE (93.74?±?1.6%) and DL (11.86?±?0.8%) compared to mPEG–PLA micelles (EE 91.89?±?1.2% and DL 11.06?±?0.8%). mPEG–PLA-Ch micelles were internalized by the cancer cells effectively and exhibited higher cytotoxicity compared to free CUR in both, murine melanoma (B16F10) and human breast cancer (MDA-MB-231) cells. mPEG–PLA-Ch exhibited satisfactory hemocompatibility indicating their potential for systemic application. Further, mPEG–PLA-Ch-CUR demonstrated higher rate of reduction of tumor volume in B16F10-xenografted tumor-bearing mice compared to free CUR. At the end of 22 days, the tumor reduced to 1.87-fold (627.72?±?0.9?mm³ versus 1174.68?±?1.64?mm³) compared to the treatment with free CUR. In conclusion, the experimental data in vitro and in vivo indicated that the newly developed CUR-mPEG–PLA-Ch micelles may have promising applications in solid tumors.     

Comparative study on the predictability of statistical models (RSM and ANN) on the behavior of optimized buccoadhesive wafers containing Loratadine and their in vivo assessment

Objective: Buccoadhesive wafer dosage form containing Loratadine is formulated utilizing Formulation by Design (FbD) approach incorporating sodium alginate and lactose monohydrate as independent variable employing solvent casting method.

Methods: The wafers were statistically optimized using Response Surface Methodology (RSM) and Artificial Neural Network algorithm (ANN) for predicting physicochemical and physico-mechanical properties of the wafers as responses. Morphologically wafers were tested using SEM. Quick disintegration of the samples was examined employing Optical Contact Angle (OCA).

Results: The comparison of the predictability of RSM and ANN showed a high prognostic capacity of RSM model over ANN model in forecasting mechanical and physicochemical properties of the wafers. The in vivo assessment of the optimized buccoadhesive wafer exhibits marked increase in bioavailability justifying the administration of Loratadine through buccal route, bypassing hepatic first pass metabolism.     

Omega-9 Modifies Viscoelasticity and Augments Bone Strength and Architecture in a High-Fat Diet-Fed Murine Model

The influence of diet on the development of osteoporosis is significant and not fully understood. This study investigated the effect of diets of varying lipid profiles and ω-3, ω-6 and ω-9 composition on the structural and mechanical properties of bone. The hypothesis studied was that a diet high in saturated fat would induce osteoporosis and produce an overall increased detrimental bony response when compared with a diet high in unsaturated ω-6, or ω-9. Male C57BL/6J mice were fed either a control diet, 50:50 mix (saturated:unsaturated) high in ω-9 (HFD^50:50), a diet high in saturated fat (HSF) or a polyunsaturated fat diet high in ω-6 (PUFA) over an 8-week duration. Tibiae were retrieved and evaluated using DMA, 3-point-bending, histomorphometry, and microCT. Mice fed a HSF diet displayed key features characteristic of osteoporosis. The loss tangent was significantly increased in the HFD^50:50 diet group compared with control (p = 0.016) and PUFA-fed animals (p = 0.049). HFD^50:50-fed mice presented with an increased viscous component, longer tibiae, increased loss modulus (p = 0.009), and ultimate stress, smaller microcracks (p < 0.001), and increased trabecular width (p = 0.002) compared with control animals. A diet high in ω-9 resulted in an overall superior bone response and further analysis of its role in bone health is warranted.     

Prevalence of signs and symptoms of ocular surface disease in individuals treated and not treated with glaucoma medication

Background: To determine the prevalence of signs and symptoms of ocular surface disease in two hospital‐based cohorts; glaucoma patients and non‐glaucoma patients. Design: A cross‐sectional, comparative case series. Participants: Glaucoma patients (n = 300) prescribed topical glaucoma medications for ≥6 months were compared with control patients (n = 100) who were not applying prescribed topical medications. Methods: A validated self‐report questionnaire was used to elicit the extent of ocular symptoms. Signs of ocular surface and eyelid disease were assessed along with medication history. Main Outcome Measures: Signs and symptoms of ocular surface pathology were determined including the tear film break‐up time, fluorescein staining of the cornea and conjunctiva, meibomian gland dysfunction and Schirmer's test. Results: A significant increase in the prevalence of ocular surface disease signs was observed in the glaucoma population, 70.3%, compared with controls, 33% (P < 0.001). The overall prevalence of clinically significant ocular surface disease symptoms was not significantly different between cohorts, 30.7% versus 24.0%, respectively (P = 0.252). Logistic regression analysis showed that the number of anti‐glaucoma medications and duration of therapy were key predictors of significant ocular surface disease signs in the glaucoma group. There was no significant correlation between signs and symptoms of ocular surface disease in either group after adjusting for age and gender. Conclusions: Signs and symptoms of ocular surface disease are relatively common in older patients, but signs of ocular surface disease are significantly higher in individuals who instil topical glaucoma therapy.     

A case of colouterine fistula managed laparoscopically

Fistulas between the uterus and bowel are rarely reported. We report successful laparoscopic management of a colouterine fistula caused by a foreign body in the uterus. Fistulas between the gastrointestinal tract and the female genital tract are usually found between the vagina and rectum as a result of complications of childbirth or iatrogenic trauma. Communication between the uterus and bowel is rarely reported. We report successful laparoscopic management of an unusual case of colouterine fistula caused by a foreign body in the uterus.     

Picosecond Bessel Beam Fabricated Pure,Gold-Coated Silver Nanostructures for Trace-Level Sensing of Multiple Explosives and Hazardous Molecules

A zeroth-order, non-diffracting Bessel beam, generated by picosecond laser pulses (1064 nm, 10 Hz, 30 ps) through an axicon, was utilized to perform pulse energy-dependent (12 mJ, 16 mJ, 20 mJ, 24 mJ) laser ablation of silver (Ag) substrates in air. The fabrication resulted in finger-like Ag nanostructures (NSs) in the sub-200 nm domain and obtained structures were characterized using the FESEM and AFM techniques. Subsequently, we employed those Ag NSs in surface-enhanced Raman spectroscopy (SERS) studies achieving promising sensing results towards trace-level detection of six different hazardous materials (explosive molecules of picric acid (PA) and ammonium nitrate (AN), a pesticide thiram (TH) and the dye molecules of Methylene Blue (MB), Malachite Green (MG), and Nile Blue (NB)) along with a biomolecule (hen egg white lysozyme (HEWL)). The remarkably superior plasmonic behaviour exhibited by the AgNS corresponding to 16 mJ pulse ablation energy was further explored. To accomplish a real-time application-oriented understanding, time-dependent studies were performed utilizing the AgNS prepared with 16 mJ and TH molecule by collecting the SERS data periodically for up to 120 days. The coated AgNSs were prepared with optimized gold (Au) deposition, accomplishing a much lower trace detection in the case of thiram (~50 pM compared to ~50 nM achieved prior to the coating) as well as superior EF up to ~10⁸ (~10⁶ before Au coating). Additionally, these substrates have demonstrated superior stability compared to those obtained before Au coating.     

Inflammatory bowel disease-related colorectal cancer: Past,present and future perspectives

Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the “common ground hypothesis”, microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the ‘inflammation-dysplasia-carcinoma’ sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons — cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.