Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic, and analgesic properties. NSAIDs are commonly used to treat conditions such as gout, arthritis, muscle pain, pyrexia, dysmenorrhea, and migraines; however, their toxicity may lead to hepatotoxicity, renal damage, and hypertension. In this study, a reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed using a central composite design (CCD). The developed method was validated for linearity, robustness, limit of detection (LOD), limit of quantification (LOQ), precision, and accuracy, and was also applied to analyze flurbiprofen nanostructured lipid carriers (NLCs) and marketed formulations, including topical gel and eye drops. The calibration curve for flurbiprofen was linear over the concentration range of 0.125–50 µg/mL. The percentage recovery at sample concentrations of 400, 500, and 600 ng was 97.79%, 100.26%, and 100.61%, respectively, indicating good accuracy. The percentage relative standard deviation (%RSD) was less than 2%, confirming the precision of the method. Robustness was demonstrated by %RSD values below 2% following deliberate variations in flow rate, injection volume, and mobile phase pH. The LOD and LOQ were determined to be 50 ng/mL and 125 ng/mL, respectively. Using the optimized method, flurbiprofen was successfully identified and quantified in NLCs as well as in marketed topical gel and eye drop formulations, producing well-resolved peaks with high accuracy, precision, and sensitivity. Comprehensive testing and validation confirmed that the developed method is suitable for routine analytical applications.
Glioblastoma multiforme (GBM) is a highly aggressive type of brain cancer known for its rapid progression and treatment resistance, presenting significant challenges for effective management. This article examines the promising potential of mesoporous silica nanoparticles (MSNs) as a groundbreaking platform for both the treatment and diagnosis of this formidable disease. MSNs boast several advantageous properties, including a large surface area, customizable pore sizes, and excellent biocompatibility. These characteristics enable efficient encapsulation of therapeutic agents, controlled release, and targeted delivery directly to GBM cells. One of the key advantages of MSNs is their ability to be functionalized with specific targeting ligands, which enhances their specificity toward tumor cells, facilitates navigation through the blood–brain barrier (BBB), and helps address the issues of tumor heterogeneity and drug resistance. When integrated with multimodal therapies, such as chemotherapy, immunotherapy, and photodynamic therapy, MSNs can create synergistic effects that improve therapeutic outcomes while reducing adverse off-target effects. Additionally, MSNs are poised to enhance diagnostic capabilities, improving imaging techniques for the accurate detection and monitoring of GBM. This review consolidates recent advancements in MSN-based approaches, emphasizing their therapeutic and diagnostic potential while also discussing toxicity concerns and outlining future pathways for clinical application to ultimately enhance patient outcomes.
Diabetic wounds stand as one of the most severe conditions of diabetes, which can be transformed into chronic, non-healing ulcers and may increase the risk of limb amputation. These complications can be prevented using a novel targeted treatment approach. In recent years, nanoformulation has emerged as a promising technique for addressing such complications. Solid lipid nanoparticles (SLNs) have attracted substantial interest due to their biocompatibility, stability, and ability to load a wide range of therapeutic agents. This review summarizes synthesis strategies and recent advancements in SLNs for the treatment of diabetic wounds. The lipid matrix of the SLNs is essential for their biocompatibility and for the encapsulation of a wide range of bioactive agents, such as growth factors. The SLNs also possess a high zeta potential and interfacial charge, which improve their stability in biological fluids and influence their interactions with the wound environment. We have also highlighted the different methods for synthesizing SLNs, including microemulsion methods, supercritical fluid methods, spray drying, etc., depending on the route of administration. The SLNs can be administered through the topical, oral, and systemic routes. The topical application of bioactive compounds loaded into SLNs helps reduce microbial load and oxidative stress at the diabetic wound site. However, oral and systemic delivery help manage oxidative stress associated with diabetes, and at the wound site, they provide a dual approach for managing the diabetic wound. Overall, SLNs represent a promising platform for the effective treatment of diabetic wounds, offering multifunctional strategies to overcome current therapeutic limitations.
Background: Breast cancer remains a significant global health concern, with conventional treatments like surgery and chemotherapy facing challenges due to poor drug selectivity and toxic effects. Nanotechnology, particularly dendrimers, is gaining attention for drug delivery as they provide targeted treatment and enhanced safety, owing to their defined size, complex structure, and ability to modify surfaces and encapsulate drugs. Materials and Methods: A thorough literature search on dendrimer-based methods for diagnosing or treating breast cancer was conducted using databases such as PubMed, Scopus, Web of Science, and ScienceDirect. The search focused on original research and review articles in English, while excluding studies on alternative nanocarriers, those lacking research substance, or unrelated to dendrimers. Results: PAMAM, PPI, polyester, carbosilane, and other dendrimer types, along with their modified derivatives, are promising for targeted drug delivery, imaging, combinatorial treatment, theranostics, and gene delivery. They enhance treatment effectiveness through active and passive targeting and reduce systemic toxicity, with preclinical and early clinical results indicating improved solubility, bioavailability, and tumor-specific drug accumulation Discussions: Dendrimers offer a versatile platform that addresses key limitations of traditional breast cancer therapies, enabling high drug loading capacity and targeted applications due to their adjustable structures. However, challenges remain in toxicity, scalability, production costs, and regulatory hurdles. Conclusion: Dendrimers have great potential for improving the detection and management of breast cancer. To ensure effective clinical application, future research must give priority to translational studies, scalable production, and safety optimisation.
Conventional empirical approaches (trial and error) to HPLC method design tend to yield fragile, non-consistent methods and lack regulatory flexibility, while Analytical Quality by Design offers a structured framework ensuring reliability. In this study a AQbD guided HPLC method was developed and optimised for Palbociclib, a Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) approved for the treatment of hormone receptor-positive breast cancer. Risk assessment (Ishikawa diagram) tool guided factor selection while Box-Behnken Design enabled optimisation through Design Expert (v.13) software. The optimised method employed a Shimpack C18 column (250 mm x 4.6 mm, 5 µm); mobile phase comprising Buffer (ammonium formate of pH 4.2 adjusted with glacial acetic acid) and Acetonitrile in the ratio 35:65; flow rate of 0.8 mL/min; injection volume of 10 µL; column oven temperature of 35°C and detection wavelength of 357 nm. Validation was performed in accordance with the ICH Q2 (R2) guidelines. The peak was eluted at 4.23 minutes, and the method demonstrated excellent linearity across 3–50 µg/mL with a correlation coefficient (R 2 ) of 0.9999, LOD of 0.75 µg/mL and LOQ of 2.27 µg/mL. Accuracy studies demonstrated recoveries between 98.91-100.88% while precision was evaluated through both intra-day and inter-day studies, consistently showing RSD deviations below 2%.
Pulmonary drug delivery is used for local treatment of lung diseases and for systemic administration of drugs requiring rapid absorption. Drug delivery to the lungs is limited by mucociliary clearance, macrophage uptake, and short residence time of inhaled formulations. Polymer-based carrier systems have therefore been explored to improve lung retention and delivery efficiency. Chitosan, a polysaccharide obtained from chitin, is biodegradable, biocompatible, and positively charged, enabling interaction with negatively charged pulmonary mucus. When formulated as nanoparticles, chitosan allows modulation of particle size, surface charge, and drug release behavior, which are critical parameters for pulmonary deposition. Chitosan nanoparticles have been investigated for delivery of small molecules, proteins, and nucleic acids in respiratory infections, inflammatory lung diseases, and lung cancer. Reported studies demonstrate improved lung localization and sustained drug release compared with conventional formulations. This review summarizes formulation approaches used for the preparation of chitosan nanoparticles for pulmonary delivery and discusses key physicochemical factors influencing their performance. Limitations related to aerosolization behavior and formulation reproducibility are also considered.
Research into drugs that can enhance cardiovascular health has been sparked by the rising prevalence of cardiovascular illnesses (CVDs). In addition to its anti-inflammatory and antioxidant qualities, Resveratrol (RES) is well known for its capacity to increase endothelial NO synthase (eNOS) activity. This page summarises RES's wide effects on energy metabolism, resilience to stress, exercise mimicking, circadian rhythm, lifespan control, and microbiome composition. This article addresses the poor and contradictory results shown in preclinical and clinical trials provides an update on the cardiovascular preventive properties of RES. The activation of AMP-activated protein kinase (AMPK), silent information regulator 1 (SIRT1), and natural antioxidant enzymes is associated with some of the positive effects of RES on the cardiovascular system. A microarray data summary indicates a strong correlation between the heart's reaction to calorie restriction and the transcriptional responses to RES. RES has been demonstrated to reduce contractile dysfunction, cardiac remodelling, and hypertrophy in several animal models of heart failure. Its preventive properties are believed to be due to several molecular pathways, including the suppression of prohypertrophic signalling molecules, enhancement of cardiac Ca2+ handling, control of autophagy, and decreases in inflammation. RES thus has the potential to be used in several novel therapeutic approaches for treating diseases such as atherosclerosis, ischemia/reperfusion damage, metabolic syndrome, heart failure, and inflammatory changes associated with ageing.
Ocular infections can affect the ocular surface and adnexal structures, intraocular structures, or both. Infections of the ocular surface and adnexa often arise from the invasion of commensals when typical barriers are compromised, which includes infectious blepharitis, conjunctivitis, keratitis, dacryocystitis, and orbital infections, among others. Intraocular infections may develop due to localised trauma or as part of a systemic condition. A variety of viruses, bacteria, fungi, protozoa, and helminths can cause intraocular illness. Occasionally, ocular abnormalities are the only external clinical indications of systemic infectious diseases. Analyzing specimens from ocular tissues or fluids can aid in diagnosing ocular infectious diseases and may help identify systemic infections. The management of ocular illnesses generally involves the topical application of antimicrobials and anti-inflammatory agents, along with targeted therapy addressing the underlying etiologies. In some cases, systemic antibacterial agents or glucocorticoids may be necessary. Addressing an inflamed or infected eye in an emergency context poses a diagnostic and therapeutic challenge for the emergency physician, with aetiology and prognoses varying from benign, self-limiting conditions to organ-threatening diseases. To address these ocular infections, the market has evolved with various therapeutics-based eye drops that are instilled specifically into the lower precorneal pocket and are regarded as the most patient-compliant method of drug delivery. Nevertheless, the efficacy of this approach is significantly reduced by the blink reflex, resulting in the loss of most of the topical dose. In this regard, nanosuspensions, which disperse hydrophobic drugs in an aqueous medium stabilised by surfactants, offer a promising strategy for mitigating ocular infections. Overall, this review aims to thoroughly examine the applicability of nanosuspensions in ocular drug delivery to target and treat infections in the human eye.
Nanozymes are nanoscale materials that function similarly to natural enzymes, offering advantages for cancer therapy when compared with traditional biological enzymes due to their enhanced enzymatic activity, stability, versatility, low cost, and their ability to alter the tumor microenvironment. This enables new cancer treatment strategies by modulating the tumor microenvironment through chemotherapy, photothermal therapy, photodynamic therapy, or starving therapy. However, challenges persist that hinder the development and use of nanozymes for cancer treatment, including difficulties in substrate selection, ongoing issues of tumor microenvironment heterogeneity, and the risk of off-target toxicities. Therefore, developing functionalization strategies to enhance nanozyme catalytic efficiency, targeting specificity, and biocompatibility can significantly enhance the success of novel nanozymes in cancer treatment. The covalent techniques for attaching peptides, polymers, and aptamers are based on EDC/NHS coupling, Click chemistry, and Schiff-base condensation. Noncovalent attachment techniques rely on reversible interactions (e.g., hydrogen bonds, π-π stacking, and electrostatic forces) to retain the native enzyme activity. While functionalization techniques improve the tumor targeting and biodistribution of nanozymes, they also enable stimulus-responsive activation of the nanozymes in the tumor microenvironment (triggered by acidic pH, glutathione, and/or H2O2) to reduce the risk of systemic toxicity. This review comprehensively discusses the classification, catalytic principles, and therapeutic applications of nanozymes, with emphasis on their role in modulating the tumor microenvironment for effective cancer therapy. Different functionalization strategies, including covalent, noncovalent, and peptide-, ligand-, and aptamer-based approaches, will be highlighted to enhance targeting, catalytic efficiency, and clinical applicability.
Phototherapy offers targeted, minimally invasive treatment for glioblastoma (GBM) with reduced systemic toxicity. Intranasal delivery bypasses the blood-brain barrier (BBB) but requires improved tumor targeting and synchronized light activation. Recent advancements in nanotechnology and smart photosensitizers have improved the selectivity and efficacy of PDT and PTT. Key challenges for GBM phototherapy include light penetration and drug retention. The future of GBM treatment may rely on combining phototherapy with personalized methods and collaborative research. Glioblastoma (GBM) is the most aggressive primary malignant brain tumor, with a median overall survival of only 14–16 months despite maximal safe resection, radiotherapy, and temozolomide. The blood–brain barrier, infiltrative growth pattern, and tumor microenvironment-mediated therapeutic resistance severely limit the efficacy of conventional and emerging therapies. Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), offers spatially selective tumor ablation through light activation, minimal invasiveness, and the ability to trigger immunogenic cell death. Recent advances in second- and third-generation photosensitizers, near-infrared-absorbing photothermal agents, and multifunctional nanoplatforms have substantially improved tumor-specific accumulation and therapeutic indices in preclinical GBM models. Intranasal administration has emerged as a clinically attractive, noninvasive route to bypass the blood–brain barrier and deliver photosensitizers and photothermal agents directly to the brain. Preclinical studies have demonstrated that combining PDT or PTT with temozolomide, immune checkpoint inhibitors, or ferroptosis inducers yields synergistic antitumor effects, prolongs survival and abscopal responses, and reduces postsurgical recurrence in orthotopic GBM models. Despite these encouraging outcomes, clinical translation is currently hindered by the depth of light penetration in the human brain, the nonuniform distribution of the drug inside the tumor, and the lack of systematic light delivery methods. To date, few phase one clinical trials of PDT have been conducted, and the findings provide the possibility of PDT intervention to increase survival rates to a certain extent. This review critically tabulates and reports the principles and approaches for the translation of multimodal phototherapy for the treatment of glioblastoma.
Everolimus, a potent mTORC1 inhibitor used in various oncological and immunological indications, requires precise quantitative analysis due to its narrow therapeutic window and susceptibility to pharmacokinetic variability. This study aimed to develop and validate a robust, sensitive, and cost-effective reverse-phase high-performance liquid chromatography method for EVR quantification in bulk drugs, marketed formulations, and nanoparticle-based delivery systems. A systematic analytical Quality by Design approach was utilized to facilitate method development and ensure method optimization. Critical method variables were identified through one-factor-at-a-time screening and subsequently optimized using a Box-Behnken Design. Thirty-seven experimental runs were evaluated to model their effects on retention time, tailing factor, theoretical plates, and peak area. The QbD-optimized chromatographic conditions, 85% ACN and 15% water, 0.85 mL/min flow rate, 50 °C column temperature, and 20 µL injection volume, detection wavelength was 278 nm yielded a high composite desirability (0.759) and produced sharp, well-resolved EVR peaks. Method validation was performed in accordance with ICH Q2(R2) guidelines, and results were found within the accepted limits. Linearity range was found to be from 100 ng/mL to 10,000 ng/mL, the coefficient of determination was 0.9965, and LOD and LOQ was found to be 50 ng/mL and 100 ng/mL, respectively. Overall, the developed RP-HPLC method is sensitive, reproducible, and suitable for routine quantification of EVR in pharmaceutical formulations and nanoformulations, providing a practical alternative to liquid chromatography with tandem mass spectrometry in resource-limited analytical settings.
The landscape of drug delivery has undergone a transformative shift with the emergence of adaptive therapeutics, smart microdevices engineered to respond dynamically to specific physiological or externally applied stimuli. These stimuli-responsive systems represent a significant advancement over conventional delivery methods by offering precise spatiotemporal control over drug release, thereby enhancing therapeutic efficacy and minimizing off-target effects and systemic toxicity. This review delves into the foundational design principles and material innovations that underpin these responsive microdevices. It highlights the role of endogenous stimuli such as pH gradients, temperature fluctuations, enzymatic activity, and redox, ionic, and hypoxia-responsive elements in activating drug release mechanisms. The integration of cutting-edge microfabrication techniques, nanomaterials, and bioinspired architectures has enabled the development of devices that are not only highly sensitive and selective but also capable of navigating complex biological environments. Furthermore, the article explores and examines the challenges associated with scalability, long-term biocompatibility, biosafety, and toxicity of implanted microdevices. Emerging trends such as AI-enhanced feedback loops, wearable biosensors, and closed-loop delivery platforms are discussed as future directions that could redefine personalized medicine. By bridging engineering ingenuity with biomedical imperatives, stimuli-responsive microdevices are poised to revolutionize drug delivery, offering intelligent, patient-centric solutions that adapt in real time to the dynamic needs of the human body. Notably, stimulus-responsive microdevices may soon facilitate localized delivery of imaging contrast agents, pharmaceuticals, genes, and mRNA; enable minimally invasive surgical procedures; and assist in cellular micromanipulation.
The aims of this work to optimize and validate a RP-HPLC method to quantify erastin (ERT) and lenalidomide (LND) in mesoporous silica nanoparticles (MSNs). The Design of Experiments (DoE) strategy optimized the RP-HPLC method. The independent variables were buffer ratio, buffer pH, flow rate and injection volume. The dependent variables were retention time (Rt), Peak area, and resolution between the peaks of the analytes. The optimized conditions were: buffer ratio 68% and methanol 32%, flow rate 0.8 mL/min, buffer pH 5.8, and injection volume 10 µL. The ICH Q2(R1) recommendations were followed in the validation of the optimized RP-HPLC method. The method demonstrated linearity of more than 0.99 for both ERT and LND. The LOD and LOQ were 0.75 and 1.62 ng/mL for ERT; for LND 31.25 and 50 ng/mL. The specificity of the established RP-HPLC method was unaffected by the MSNs matrix. The drugs-loaded MSNs were analyzed using the suggested RP-HPLC technique. The % entrapment efficiency of ERT and LND was found to be 72.65 and 79.50%, and drug loading of ERT and LND was found to be 14 and 17% in MSNs, respectively. The optimized RP-HPLC method was used to check the in-vitro drug release of the ERT and LND from the ERT-LND@MSNs. Surface properties of synthesized MSNs was checked through particle and SEM analysis. The developed analytical method was eco-friendly according to AGREE analysis and GAPI analysis.
Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic frameworks, demonstrate enhanced targeting and therapeutic efficacy through HSP70 modulation. Functionalized nanocarriers exploit HSP70's tumour-specific overexpression to improve drug delivery, minimise off-target effects and overcome the blood-brain barrier. Emerging strategies such as chemophototherapy, immunotherapy and photothermal therapy leverage HSP70's interactions within the tumour microenvironment, enabling synergistic treatment modalities. The review also highlights translational challenges, including heterogeneity of GBM, regulatory hurdles and variability in the enhanced permeability and retention (EPR) effect. Integrating computational modelling, personalised approaches and adaptive trial designs is crucial for clinical translation. By bridging nanotechnology and molecular biology, HSP70-targeted strategies hold transformative potential to redefine GBM diagnosis and treatment, offering hope for improved survival and quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT00054041 and NCT04628806.
Helicobacter pylori, a Gram-negative bacterium, exhibits unique adaptations to thrive in an acidic gastric environment. Urease enzyme present in the bacteria converts urea to ammonia and carbon dioxide, making the surrounding acidic environment of the bacteria neutral. This adaptation helps the bacteria to survive and travel further to gastric epithelial cells, where it attaches to mucin and damages the tissues, leading to gastritis, peptic ulcer, and ultimately, cancer. Physicians typically prescribe first-, second-, and third-line antibiotic therapies to eliminate the bacterium, but these treatments frequently fail to achieve complete eradication. This failure, driven by factors such as the coccoid form, high bacterial load, and biofilm formation, contributes to the growing problem of antibiotic resistance. Targeting urease activity presents a promising strategy to reduce the H. pylori pathogenicity and enhance its susceptibility to antibiotics. Inhibiting urease enzyme activity would be an option to make the bacteria less pathogenic and more prone to antibiotic treatment. Including the urease inhibitors as an adjuvant with the current antibiotic treatment regimen would effectively eradicate the bacteria. This comprehensive review discusses the structural characteristics of the urease enzyme and its role in pathogenesis and the available urease inhibitors along with their pharmacophoric features. An elaborative pharmacophore-based screening and docking study on scaffolds such as chlorogenic acid, catechol, and hydroxamic acid to discover a potent urease inhibitor is a future scope identified in this review.