DEVELOPMENT AND CHARACTERIZATION OF TOPICAL OPHTHALMIC FORMULATIONS CONTAINING LUTEIN-LOADED MUCOADHESIVE NANOPARTICLES

Objective: To develop and characterize a topical ophthalmic formulation containing chitosan-dextran sulfate nano particles (CDNs) for enhanced ocular bioavailability and stability of lutein.Methods: Lutein-loaded CDNs (LCDNs) were prepared by polyelectrolyte complexation employing oppositely charged polymers, chitosan and dextran sulfate. Effects of the polymer mass ratios, the total amount of polymers, and the amount of EDC and PEG400 on their physicochemical properties as well as the drug release profiles were investigated. The physicochemical stability of LCDNs dispersed in various ophthalmic vehicles and the accompanying microbial contamination were also evaluated.Results: LCDNs possessed a mean size of ~400 nm with a positive surface charge of+30 mV and entrapment efficiency up to 75%. Dissolution profiles followed a Higuchi's square root model, indicating a diffusional release mechanism. LCDNs dispersed in Feldman ophthalmic buffer showed good physical stability with no microbial contamination. The chemical stability of lutein was significantly improved in LCDNs and further improved by the addition of antioxidant in the ophthalmic vehicle.Conclusion: The ophthalmic formulation containing LCDNs, developed in this work, has characteristics suitable for application in ocular surface drug delivery systems.Keywords: Chitosan, dextran sulfate, Nanoparticles, Ophthalmic vehicle, Lutein

DEVELOPMENT AND CHARACTERIZATION OF INDOMETHACIN-LOADED MUCOADHESIVE NANOSTRUCTURED LIPID CARRIERS FOR TOPICAL OCULAR DELIVERY

Objective: To develop and characterize indomethacin loaded-nanostructured lipid carriers (IND-NLCs) for topical ophthalmic delivery with different particle sizes and polymer coating to improve the mucoadhesive property on the ocular surface.Methods: Nanostructured lipid carriers (NLCs) with different solid lipids and surfactants were prepared by the high-pressure homogenization technique. The optimized IND-NLCs was coated with polyethylene glycol 400 (PEG). The physicochemical properties and entrapment efficacy (EE) were examined. In vitro release studies were investigated using the shake-flask method. Ex vivo mucoadhesive studies were assessed by the wash-off test. In addition, the cytotoxicity was assessed by the short time exposure test.Results: IND-NLCs of ~300 and ~40 nm in diameter were successfully produced with a zeta potential of -30 mV and EE of 60–70 %. IND-NLCs prepared with Tween 80 as surfactant could be sterilized by autoclaving. The PEG coating of IND-NLCs did not affect either the particle size or EE. In vitro release showed a prolonged release for 360 min with a burst release of 50-60% occurring within 5 min. The smaller-sized IND-NLCs showed slightly faster release rates and better mucoadhesion to cornea compared to the larger IND-NLCs. PEG-coated IND-NLCs showed the highest mucoadhesion. In addition, IND-NLCs showed less cytotoxicity compared to IND alone. Conclusion: The small and PEG-coated NLCs represents a potentially useful carrier for safe delivery of indomethacin to the ocular surface with increased residence time

PENETRATION OF HYDROPHILIC SULFORHODAMINE B ACROSS THE PORCINE CORNEA EX-VIVO

Objective: Sulforhodamine B (SRB) is a hydrophilic tracer whose fluorescence is unaffected by pH unlike that of carboxyfluorescein. Therefore, SRB may serve as a better tracer when there are significant changes in pH. Thus, in this study, the suitability of SRB to assess the barrier properties of the cellular layers of the cornea was examined using a custom-built confocal scanning micro-fluorometer (CSMF). Methods: The dye solution (0.1% SRB) was prepared in PBS-Ca2+and three experiments were performed ex vivo using freshly isolated porcine eyes. First, we investigated the penetration of SRB across the endothelium by injection of the dye into the anterior chamber. Next, we measured the penetration of SRB across the epithelium after exposing the ocular surface to the dye. Finally, we examined the penetration after exposure to the dye with detergent (Tween 20) and exposure to the dye concomitant with microneedle injuries. The dye concentration profiles across the cornea were measured using CSMF.Results: SRB penetrated the corneal endothelium readily into the stroma following injection into the anterior chamber in a time-dependent manner. Despite accumulation in the stroma, SRB did not partition into the epithelium. In agreement with these findings, the dye did not cross the epithelium after topical administration. Co-administration with Tween 20 and injury to the epithelium with microneedles, however, led to penetration of the dye into the stroma.Conclusions: SRB is a hydrophilic dye that can be used as an alternative fluorescent tracer to assess the barrier function of the cellular layers of the cornea

INTERACTION OF NANOSTRUCTURED LIPID CARRIERS WITH HUMAN MEIBUM

Objective: This study aimed to determine the possibility of nanostructured lipid carriers (NLCs) as a bionic tear film by determining the surface activities of the developed NLCs and their interaction with human meibomian lipid films. Methods: NLCs with different types of solid lipids and surfactants were prepared by a high-pressure homogenizer. The particle size was determined by dynamic light scattering. The surface activities of the NLCs and NLCs mixed with meibomian lipids were measured using a Langmuir trough and the resulting surface pressure area (Π-A) profiles were compared. These lipid films were further analyzed using fluorescence microscopy and scanning electron microscopy (SEM). Results: The particle size of prepared NLCs varied from 38–280 nm based on types of solid lipid and surfactant. All NLCs were highly surface active as indicated by their maximum surface pressure (Πmax). The Π-A profiles of meibum seeded with NLCs showed higher surface pressure than meibum alone and the shape of profiles were dominated by the meibomian lipids. These findings were in agreement with fluorescence and SEM micrographs, which revealed that the NLCs could adsorb and integrate to the meibomian lipid films as well as diffuse from the subphase to the lipid films. Conclusion: NLCs are surface active and can integrate with meibomian lipid films formed stable films. The type of interaction can be tailored by altering the solid lipids used in the formulation of the NLCs which could provide the means to develop efficient formulations for targeting dry eye disease related to a non-functional tear film lipid layer

Streptococcus agalactiae in adults at chiang mai university hospital: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Infection caused by <it>Streptococcus agalactiae</it>, a Group B streptococcus, is an emerging disease in non-pregnant adults. This study describes the epidemiological, clinical, and microbiological characteristics of <it>S. agalactiae </it>infection in adult patients in northern Thailand.</p> <p>Methods</p> <p>A retrospective study was conducted between January 1, 2006 and December 31, 2009 at Chiang Mai University Hospital among patients aged ≥15 years, whose clinical specimens obtained from normally sterile sites grew <it>S. agalactiae</it>.</p> <p>Results</p> <p>One-hundred and eighty-six patients and 197 specimens were identified during the 4-year period. Among 186 patients, 82 were documented as having invasive infection; 42 patients were male (51.2%) with the mean age of 48.5 ± 19.4 years (range 17, 83). Fifty-three patients (64.6%) had underlying medical conditions; 17 patients (20.7%), 10 (12.2%), 8 (9.7%) had diabetes, chronic renal diseases, and malignancy, respectively. Among 40 patients (48.8%) with bloodstream infection, no other site of infection was determined in 29 (35.4%) patients. In the remaining 11 patients, 5 patients (6.1%), 5 (6.1%), and 1 (1.2%) had meningitis, arthritis, and meningitis with arthritis, respectively. Forty-two patients (51.2%) presented with localized infection, i.e., subcutaneous abscess (19 patients, 23.2%), chorioamnionitis (10 patients, 12.2%), urinary tract infection (5 patients, 6.1%), arthritis (3 patients, 3.7%), meningitis (2 patients, 2.4%), and spontaneous bacterial peritonitis, uveitis, and tracheobronchitis (1 patient each, 1.2%). The overall mortality was 14.6% (12 patients).</p> <p>Conclusions</p> <p><it>S. agalactiae </it>infection is a growing problem in non-pregnant patients, particularly in those with underlying medical conditions. Physicians should add <it>S. agalactiae </it>infection in the list of differential diagnoses in patients with meningitis and/or septicemia.</p

Efficacy and Clinicogenomic Correlates of Response to Immune Checkpoint Inhibitors Alone or With Chemotherapy in Non-Small Cell Lung Cancer

The role of combination chemotherapy with immune checkpoint inhibitors (ICI) (ICI-chemo) over ICI monotherapy (ICI-mono) in non-small cell lung cancer (NSCLC) remains underexplored. In this retrospective study of 1133 NSCLC patients, treatment with ICI-mono vs ICI-chemo associate with higher rates of early progression, but similar long-term progression-free and overall survival. Sequential vs concurrent ICI and chemotherapy have similar long-term survival, suggesting no synergism from combination therapy. Integrative modeling identified PD-L1, disease burden (Stage IVb; liver metastases), and STK11 and JAK2 alterations as features associate with a higher likelihood of early progression on ICI-mono. CDKN2A alterations associate with worse long-term outcomes in ICI-chemo patients. These results are validated in independent external (n = 89) and internal (n = 393) cohorts. This real-world study suggests that ICI-chemo may protect against early progression but does not influence overall survival, and nominates features that identify those patients at risk for early progression who may maximally benefit from ICI-chemo

Predicting Benefit From Immune Checkpoint Inhibitors in Patients With Non-Small-Cell Lung Cancer by CT-Based Ensemble Deep Learning: A Retrospective Study

BACKGROUND: Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context. METHODS: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from Jan 1, 2014, to Feb 29, 2020. We built and tested an ensemble deep learning model on pretreatment CTs (Deep-CT) to predict overall survival and progression-free survival after treatment with immune checkpoint inhibitors. We also evaluated the added predictive value of the Deep-CT model in the context of existing clinicopathological and radiological metrics. FINDINGS: Our Deep-CT model demonstrated robust stratification of patient survival of the MD Anderson testing set, which was validated in the external Stanford set. The performance of the Deep-CT model remained significant on subgroup analyses stratified by PD-L1, histology, age, sex, and race. In univariate analysis, Deep-CT outperformed the conventional risk factors, including histology, smoking status, and PD-L1 expression, and remained an independent predictor after multivariate adjustment. Integrating the Deep-CT model with conventional risk factors demonstrated significantly improved prediction performance, with overall survival C-index increases from 0·70 (clinical model) to 0·75 (composite model) during testing. On the other hand, the deep learning risk scores correlated with some radiomics features, but radiomics alone could not reach the performance level of deep learning, indicating that the deep learning model effectively captured additional imaging patterns beyond known radiomics features. INTERPRETATION: This proof-of-concept study shows that automated profiling of radiographic scans through deep learning can provide orthogonal information independent of existing clinicopathological biomarkers, bringing the goal of precision immunotherapy for patients with NSCLC closer

A study using Andrographis paniculata in diet on growth performance of Betong chicken: Starting period

An eight-week experiment was conducted to study using Andrographis paniculata (AP) on the growth performance of Betong chickens (0-8 weeks of age). Three hundred and fifteen head of 1 day old (mixed sex) betong chicks were randomly allotted to 7 dietary treatments, in a completely randomized design experiment. There were three replications in each treatment with 15 chicks per pen. The dietary treatments were 1) basal diet (control), 2) basal diet + 0.1% AP, 3) basal diet + 0.2% AP, 4) basal diet + 0.3% AP, 5) basal diet + 0.5% AP, 6) basal diet + 0.6% AP and 7) basal diet + antibiotic 0.2%, respectively. The results showed no significant (P>0.05) difference among treatments in terms of weight gain, feed intake, feed conversion, mortality rate and feed cost when AP was included up to 0.1-0.3 % of the diet compared with basal diet and basal diet + antibiotic. However, at levels higher than 0.5% AP, it tended to lower growth performance and feed intake thus causing inferior feed conversion ratio. Feed cost was also dramatically increased with the increasing levels of AP in the diet. No significant difference in mortality rate was found among groups. The average mortality was 1.37%