METHODS: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages.
RESULTS: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls.
CONCLUSION: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.
OBJECTIVE: Ternary copper (II) complex incorporated with 1-10-phenanthroline and L-tyrosine was investigated for its anti-cancer effects in HT-29 colorectal cancer cells.
METHODS: Cytotoxic effects of ternary copper (II) complex in HT-29 cells were evaluated using MTT assay, Real-Time Cell Analysis (RTCA), and lactate dehydrogenase (LDH) assay. Cell cycle analysis was performed using flow cytometry. Apoptosis induction was studied by Annexin V-FITC/propidium iodide (PI) staining and mitochondrial membrane potential analysis (JC-10 staining) using flow cytometry. Intracellular reactive oxygen species (ROS) were detected by DCFH-DA assay. The expression of proteins involved in the apoptotic signalling pathway (p53, caspases, and PARP-1) was evaluated by western blot analysis.
RESULTS: Ternary copper (II) complex reduced the cell viability of HT-29 cells in a time- and dose-dependent manner, with IC50 of 2.4 ± 0.4 and 0.8 ± 0.04 µM at 24 and 48 hours, respectively. Cell cycle analysis demonstrated induction of S-phase cell cycle arrest. Morphological evaluation and Annexin V-FITC/PI flow cytometry analysis confirmed induction of apoptosis that was further supported by cleavage and activation of caspase-8, caspase-9, caspase-3, and PARP-1. Mutant p53 was also downregulated in a dose-dependent manner. No LDH release, mitochondrial membrane potential disruption, and ROS production were observed.
CONCLUSION: Ternary copper (II) complex holds great potential to be developed for colorectal cancer treatment.
METHOD: This cross-sectional study was conducted in 14 Perak state hospitals and 12 primary health clinics through an online survey. All ward pharmacists and trainee pharmacists with at least 1 month of ward pharmacy experience and working in government-funded health facilities were included. The validated survey tool consisted of demographic characteristics, pharmacists' experience towards challenges (22 items), and their attitude towards adaptive measures (9 items). Each item was measured based on a 5-point Likert scale. One-way ANOVA and logistic regression were employed to determine the association of pharmacists' characteristics against their experience and attitude.
RESULTS: Out of 175 respondents, 144 (81.8%) were female, and 84 (47.7%) were Chinese. Most pharmacists served in the medical ward (124, 70.5%). Commonly reported perceived challenges were difficulties in counselling medication devices (3.63 ± 1.06), difficulties in clerking medication history from family members (3.63 ± 0.99), contacting family members (3.46 ± 0.90), patient's digital illiteracy in virtual counselling (3.43 ± 1.11) and completeness of the electronic records (3.36 ± 0.99). For attitude towards adaptive measures, improving internet connection (4.62 ± 0.58), ensuring availability of multilingual counselling videos (4.45 ± 0.64), and provision of internet-enabled mobile devices (4.39 ± 0.76) were the most agreeable by the pharmacists. Male (AOR: 2.63, CI 1.12-6.16, p = 0.026) and master's degree holders (AOR: 2.79, CI 0.95-8.25, p = 0.063) had greater odds of high perceived challenging experience scores. Master's degree holders (AOR: 8.56, CI 1.741-42.069, p = 0.008) were also more likely to have a positive attitude score towards adaptive measures.
CONCLUSION: Pharmacists faced multiple challenges in the ward pharmacy practice during the COVID-19 pandemic, especially in medication history assessment and patient counselling. Pharmacists, especially those with higher levels of education and longer tenure, exhibited a higher level of agreement towards the adaptive measures. The positive attitudes of pharmacists towards various adaptive measures, such as improvement of internet infrastructure and digital health literacy among patients and family members, warrant immediate action plans from health authorities.
METHODS: The study involved conducting intradermal injections on four cadavers and participants using a 2 mm length, 34-gauge needle (N-Finders, Inc., South Korea). During the cadaveric study, the polynucleotide prefilled syringe was dyed green, and an anatomist performed dissections, removing only the skin layer. Ultrasonographic observations were carried out to ensure accurate intradermal injection placement.
RESULTS: In all four cadavers, the facial injections at the anterior cheek region were precisely administered intradermally at a 30-degree injection angle. However, the 90-degree injection was found just below the dermal layer upon skin layer removal.
DISCUSSION: The findings suggest that using a 2 mm needle length allows for easy and convenient intradermal injections.