Advancing Ocular Medication Delivery with Nano-Engineered Solutions: A Comprehensive Review of Innovations, Obstacles, and Clinical Impact.

Recent advancements in ocular drug delivery have led to the introduction of a range of nanotechnology-based systems, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, inorganic nanoparticles, niosomes, liposomes, nanosuspensions, dendrimers, nanoemulsions, and microemulsions. These systems enhance drug retention, penetration, bioavailability, and targeted delivery, promising prolonged drug release, and improved patient compliance. However, their interactions with biological systems pose potential toxicity risks, necessitating a careful evaluation of nanoparticle size, shape, surface charge, and coating. Traditional ocular drug delivery methods, like topical applications and injections, face challenges due to anatomical and physiological barriers, leading to frequent dosing and systemic toxicity risks. Nanocarriers offer solutions by improving drug permeation and targeted delivery, yet translating these innovations from research to clinical practice involves overcoming hurdles related to manufacturing scale-up, quality control, regulatory approval, and cost-effectiveness. The quality by design (QbD) framework provides a systematic approach to optimize nanocarrier formulation and process design, ensuring safety and efficacy. Assessing the safety of nanocarriers through in vivo and in vitro studies is crucial for their clinical application. This review explores the use of various nanomedicines in ocular drug delivery, highlighting the current state of ocular medication delivery and considering critical aspects such as scaling up and clinical applications.

Development of a Stable Lyophilized Cyclophosphamide Monohydrate Formulation Using Non-Aqueous Solvents.

To ensure product stability, it is critical to maintain the monohydrate state of cyclophosphamide following lyophilization, as this is the most stable solid form of the Cyclophosphamide. On the other hand, because of their limited aqueous solubility and stability, non-aqueous solvents are preferred for determining the composition and stability of bulk solutions. Hence, the purpose of this study was to use non-aqueous solvents for determining the composition and stability of bulk solutions, and to shorten the lyophilization process by retaining the cyclophosphamide monohydrate. Furthermore, prior to selecting the solvent for the bulk solution consisting of 90:10 tertiary butyl alcohol (TBA) and acetonitrile (ACN), various factors were taken into account, including the freezing point, vapor pressure of solvents, solubility, and stability of cyclophosphamide monohydrate. The concentration of the bulk solution was adjusted to 200 mg/mL in order to optimize the fill volume, enhance sublimation rates at lower temperatures during primary drying, and eliminate the need for secondary drying. The differential scanning calorimetry (DSC) measurements of bulk solution were used to improve the lyophilization cycle. The lyophilization cycle opted was freezing at a temperature of -55 °C with annealing step at -22 °C by which the reconstitution time was significantly reduced. The drying was performed at below - 25 °C while maintaining a chamber pressure of 300 mTorr. The complete removal of non-aqueous solvents was achieved by retaining water within the system. The presence of cyclophosphamide monohydrate was confirmed using X-ray diffraction (XRD). The reduction of lyophilization process time was established by conducting mass transfer tests and evaluating the physicochemical properties of the pharmaceutical product. Using non-aqueous solvents for freeze-drying cyclophosphamide is a viable option, and this study provides significant knowledge for the advancement of future generic pharmaceuticals.

A Systematic Study on Long-acting Nanobubbles: Current Advancement and Prospects on Theranostic Properties.

Delivery of diagnostic drugs via nanobubbles (NBs) has shown to be an emerging field of study. Due to their small size, NBs may more easily travel through constricted blood vessels and precisely target certain bodily parts. NB is considered the major treatment for cancer treatment and other diseases which are difficult to diagnose. The field of NBs is dynamic and continues to grow as researchers discover new properties and seek practical applications in various fields. The predominant usage of NBs in novel drug delivery is to enhance the bioavailability, and controlled drug release along with imaging properties NBs are important because they may change interfacial characteristics including surface force, lubrication, and absorption. The quick diffusion of gas into the water was caused by a hypothetical film that was stimulated and punctured by a strong acting force at the gas/water contact of the bubble. In this article, various prominent aspects of NBs have been discussed, along with the long-acting nature, and the theranostical aspect which elucidates the potential marketed drugs along with clinical trial products. The article also covers quality by design aspects, different production techniques that enable method-specific therapeutic applications, increasing the floating time of the bubble, and refining its properties to enhance the prepared NB's quality. NB containing both analysis and curing properties makes it special from other nano-carriers. This work includes all the possible methods of preparing NB, its application, all marketed drugs, and products in clinical trials.

Computational drug-drug interaction prediction mediated by CYP450 isoforms of Ilaprazole coadministered with clopidogrel.

Ilaprazole due to its pharmacokinetic variability does not affect the clopidogrel efficacy during concomitant use. Methodology: Prediction of DDI for Clopidogrel and PPIs performed using (DDI-Pred) Way2Drug software. The probabilities ΔP, which estimate the potential DDIs resulting from interaction with CYP450 isoenzymes. Results: Positive ΔP-values for CYP2C19 (0.955) indicate that it is involved in the drug interaction of Ilaprazole and Clopidogrel. Discussion: Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition Conclusion: Compared with other PPIs, Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition; Since Ilaprazole has pharmacokinetic variability, further in vivo and in vitro studies are required on the ilaprazole and clopidogrel combination to assess the effect of drug-drug interaction.

Curcumin- ß-Cyclodextrin Molecular Inclusion Complex: A Water-Soluble Complex in Fast-dissolving Tablets for the Treatment ofNeurodegenerative Disorders.

BACKGROUND: Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, ß-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders. OBJECTIVES: The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- ß-cyclodextrin molecular inclusion complex using a 32-factorial design. METHODS: The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-ß-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models. RESULTS: Post-compression parameters, i.e., hardness (4.4-5 kg/cm2), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (< 1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor. CONCLUSION: The current study reveals the validated curcumin-ß-cyclodextrin inclusion complex fastdissolving tablets with SSG and Neusilin® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

Development and characterization of novel surface engineered Depofoam: a QbD coupled failure modes and effects analysis risk assessment-based optimization studies.

This study aimed to design and develop novel surface-engineered Depofoam formulations to extend the drug delivery to the prescribed time. The objectives are to prevent the formulation from burst release, rapid clearance by tissue macrophages, and instability and to analyze the impact of process and material variables in the characteristics of formulations. This work employed a quality-by-design coupled failure modes and effects analysis (FMEA)-risk assessment strategy. The factors for the experimental designs were chosen based on the FMEA results. The formulations were prepared by the double emulsification method followed by surface modification and characterized in terms of critical quality attributes (CQAs). The experimental data for all these CQAs were validated and optimized using the Box-Behnken design. A comparative drug release experiment was studied by the modified dissolution method. Furthermore, the stability of the formulation was also assessed. In addition, the impact of critical material attributes and critical process parameters on CQAs was evaluated using FMEA risk assessment. The optimized formulation method yielded high encapsulation efficiency (86.24 ± 0.69%) and loading capacity (24.13 ± 0.54%) with an excellent zeta potential value (-35.6 ± 4.55mV). The comparative in vitro drug release studies showed that more than 90% of the drug's release time from the surface-engineered Depofoam was sustained for up to 168 h without burst release and ensured colloidal stability. These research findings revealed that Depofoam prepared with optimized formulation and operating conditions yielded stable formulation, protected the drug from burst release, provided a prolonged release, and sufficiently controlled the drug release rate.

Sustainable bioactivity enhancement of ZnO-Ag nanoparticles in antimicrobial, antibiofilm, lung cancer, and photocatalytic applications.

Cancer, microbial infections, and water pollution are significant challenges the modern human population faces. Traditional treatments for cancer and infections often have adverse effects and ecological consequences, while chemical methods for water decontamination can produce harmful byproducts. Metal nanoparticles, particularly zinc oxide (ZnO) and silver (Ag) nanoparticles, show promise in addressing these issues. However, doping Ag on ZnO NPs may synergistically enhance biomedical and therapeutic effects with fewer adverse consequences and improved photocatalytic properties for wastewater treatment. This study aimed to create ZnO and ZnO-Ag nanoparticles through green synthesis and compare their anticancer, antimicrobial, and photocatalytic activity mechanisms. XRD studies determined the crystal diameters of ZnO NPs and ZnO-Ag NPs to be 12.8 nm and 15.7 nm, respectively, with a hexagonal wurtzite structure. The XPS and EDS analyses confirmed the presence of Ag on the ZnO NPs. ZnO NPs and ZnO-Ag NPs exhibited low aggregation in aqueous suspensions, with zeta potentials of -20.5 mV and -22.7 mV, respectively. Evaluating antimicrobial and antibiofilm activity demonstrates that ZnO-Ag NPs have superior potential to ZnO NPs and standard antibiotic drugs against E. coli, S. typhi, B. subtilis, S. aureus, C. albicans, and A. niger. The results of the in vitro cytotoxicity test indicated that on the NCI-H460 lung cancer cell line, ZnO NPs and ZnO-Ag NPs demonstrated IC50 values of 40 µg mL-1 and 30 µg mL-1, respectively. The photocatalytic degradation of methylene blue under direct sunlight revealed that ZnO and ZnO-Ag NPs degraded MB by 98% and 70% in 105 min, respectively. These results show that these nanomaterials may have great potential for treating the aforementioned issues.

Assessment on infection prevention and control knowledge among medical professionals in south Indian population.

INTRODUCTION: Healthcare workers are always at higher risk of biological exposure as the healthcare setting is hazardous, and it is impracticable to exclude infection. Poor compliance with standard precautions among healthcare workers is one of the leading causes of healthcare-associated infections. This study analyzed the gaps in knowledge, attitude, and practice of infection control among healthcare workers and the influence of the COVID-19 pandemic, internet, and social media usage on infection control. METHODOLOGY: A cross-sectional study was conducted from 1st to 31st March 2022 among various healthcare professionals using a self-administered structured questionnaire to evaluate knowledge, attitude, and practice on infection control. The impact of COVID-19, Internet, and social media usage on infection control practices was also analyzed. RESULTS: Among 382 healthcare workers who participated in the study, 89.4% of the participants had good knowledge, 55.26% had a neutral attitude, and all showed good practice levels on infection control. Similarly, the result showed that internet and social media usage during COVID-19 had significantly enhanced the knowledge, attitude, and practice on infection control. CONCLUSIONS: Healthcare professionals must be frequently updated on infection control guidelines and routine training programs. The hospital's adherence to the Joint Commission International (JCI) guidelines reduces the risk of healthcare-associated infections. As observed in this study, due to the prominent influence of social media and the internet, these platforms can be exploited to provide training and awareness to healthcare professionals and the public.

Protective role of hispolon and its derivatives against apoptosis in cortical neurons induced by electromagnetic radiation from 4G mobile phone.

Electromagnetic radiation (EMR) from wireless devices, particularly mobile phones, is a potentially growing public health concern. In this study, the neuronal effects of EMR on primary cortical neurons (PCNs) from neonatal rat cerebral cortex and the protective role of hispolon (HIS) and its derivatives were investigated as a measure of cranial exposure during mobile phone use. PCNs were isolated and cultured from day-old neonatal rats, then exposed for 2 h to EMR emitted by a mobile phone operating at a frequency of 2100 MHz with 1.6 W/Kg specific absorption rate (SAR) in call-answered mode treated with HIS and its derivatives. The induction of apoptosis through modulation of pro and anti-apoptotic genes via mitochondrial pathway and the protection by the test compounds was assessed. Pyrazole derivatives decreased apoptosis by modulating the levels of pro and anti-apoptotic genes by reducing the levels of reactive oxygen species (ROS) via mitochondrial damage, which was observed in the EMR exposed PCNs. The pyrazole compounds were found to have antioxidative and anti-apoptotic properties. Thus, the neuroprotective mechanisms of the pyrazole derivatives can be investigated further, which may make them appropriate as lead compounds in developing neuroprotective formulations.

Rationale utilization of phospholipid excipients: a distinctive tool for progressing state of the art in research of emerging drug carriers.

Phospholipids have a high degree of biocompatibility and are deemed ideal pharmaceutical excipients in the development of lipid-based drug delivery systems, because of their unique features (permeation, solubility enhancer, emulsion stabilizer, micelle forming agent, and the key excipients in solid dispersions) they can be used in a variety of pharmaceutical drug delivery systems, such as liposomes, phytosomes, solid lipid nanoparticles, etc. The primary usage of phospholipids in a colloidal pharmaceutical formulation is to enhance the drug's bioavailability with low aqueous solubility [i.e. Biopharmaceutical Classification System (BCS) Class II drugs], Membrane penetration (i.e. BCS Class III drugs), drug uptake and release enhancement or modification, protection of sensitive active pharmaceutical ingredients (APIs) from gastrointestinal degradation, a decrease of gastrointestinal adverse effects, and even masking of the bitter taste of orally delivered drugs are other uses. Phospholipid-based colloidal drug products can be tailored to address a wide variety of product requirements, including administration methods, cost, product stability, toxicity, and efficacy. Such formulations that are also a cost-effective method for developing medications for topical, oral, pulmonary, or parenteral administration. The originality of this review work is that we comprehensively evaluated the unique properties and special aspects of phospholipids and summarized how the individual phospholipids can be utilized in various types of lipid-based drug delivery systems, as well as listing newly marketed lipid-based products, patents, and continuing clinical trials of phospholipid-based therapeutic products. This review would be helpful for researchers responsible for formulation development and research into novel colloidal phospholipid-based drug delivery systems.

Brain targeted delivery of anticancer drugs: prospective approach using solid lipid nanoparticles.

A brain tumour is amongst most devastating and challenging condition to overcome with suitable treatment as the drug has to cross the blood-brain barrier (BBB) with several physiological barriers like opsonisation by the reticuloendothelial system. Presently various techniques such as surgical, chemotherapeutic agents, and radiotherapy techniques have performed to extend the lifespan of patients diagnosed with glioblastoma, which did not maximise the overall survival of patients with a tumour. Nanotechnology is relied upon to diminish the requirement for intrusive methods for conveyance of therapeutics to the central nervous system. Colloidal nanocarriers sizing range 1-1000 nm have been utilised to cross BBB delivers the drug at cell levels with enhanced bioavailability and reduced toxicity. However, solid lipid nanoparticles (SLNs) are considered a highly flexible carrier for more successful remedially in brain tumour. The treatment of a brain tumour via SLNs is gaining greater potency due to its inimitable size and lipidic nature. This review focuses and represents the current strategies of SLNs in the brain tumour treatment with appropriate techniques adopted are highlighted. Based on this review, the authors concluded that SLNs embrace exclusive promising lipidic nanocarrier that could be utilised to target a brain tumour effectively.

Safety, Efficacy, and Bioavailability of Fixed-Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review.

PURPOSE: Type 2 diabetes mellitus (T2DM) is a multifactorial disease characterized by insulin resistance. As time progresses, monotherapy often does not provide effective glycemic control, generating the need for an add-on therapy. Hence, multiple oral hypoglycemic agents formulated as a single-dose form called fixed-dose combinations (FDCs) play an essential role in glycemic control. The purpose of this systematic review is to appraise the recently published evidence on the safety, efficacy, and bioavailability of FDCs. METHODS: A comprehensive literature search of PUBMED, Scopus, ScienceDirect.com, ProQuest, SpringerLink, clintrials.gov, Embase, and EBSCO using the key words FDCs, combination therapy, T2DM management, and add-on therapy was conducted. Studies on the safety profile/tolerability, efficacy, and bioavailability of various FDCs of oral hypoglycemic agents were preferred. FINDINGS: The systematic review of all the publications suggests that FDCs of oral hypoglycemic agents (OHAs) significantly reduce HbA1c and fasting plasma glucose values, thereby efficiently reducing hyperglycemia in patients in whom monotherapy fails. FDCs are the bioequivalent of the concomitant drugs administered as individual components. Improved adherence to FDCs and the absence of serious adverse drug reactions compared with dual therapy play an important role in decreasing the incidence of hyperglycemia in patients with T2DM. IMPLICATIONS: From this updated review, it was found that metformin was the most widely used component of FDCs with other OHAs. Studies on the safety and efficacy of newly approved OHAs such as sodium glucose cotransporter inhibitors were limited. An increasing number of randomized trials on the safety and efficacy of newly emerging FDCs suggests that they would be better treatment options for T2DM patients.