Tuberculosis (TB), particularly its multi-drug-resistant (MDR-TB) forms, remains a significant global health challenge. This study focused on developing and evaluating Mesoporous Silica Nanoparticles (MSNPs) as a delivery platform for D-Cycloserine (DCS) and Moxifloxacin (MXF) to enhance treatment efficacy. Specifically, this research investigated MSNP co-encapsulation (DCS-MXF@MSNPs). The dual-drug formulation was optimized using Central Composite Design (CCD), achieving an entrapment efficiency (

Abstract Phytoconstituents exhibit various effects, including antidiabetic, anticancer, cardioprotective, antioxidant, neuroprotective, and anti-infective effects. Across all the phytoconstituents, melatonin (MLT) has several beneficial effects. Basically, melatonin is secreted by the pineal gland. It is also available in most plants and plays key roles as a free radical scavenger, a potential agent for adjuvant therapy in cancer, a regulator of circadian rhythm, a management of insomnia (maintenance of the sleep cycle), an immunomodulatory agent, an anti-inflammatory agent, and more. Due to its low oral solubility, soya lecithin nanovesicles can help enhance its bioavailability. But detecting melatonin in nanovesicles is challenging. So, here we developed and validated a UV–visible spectrophotometric method for detecting melatonin in the nanovesicles. The method was developed in a buffer at a pH of 7.4. At a wavelength of 278 nm and over a concentration range of 6–36 µg mL –1 , the coefficient of determination was 1.0, confirming linearity. The method was also demonstrated to be precise, sensitive, robust, reproducible, and accurate. In silico toxicity predicted respiratory toxicity (84 %) and BBB toxicity (84 %). This analytical method can be used to predict MLT in nanostructured products, large-dose forms, and various pharmaceutical preparations.

Antisense oligonucleotides represent a promising class of therapeutic agents due to their high specificity in modulating gene expression. These short, single-stranded synthetic sequences (typically 13-25 nucleotides) function by binding to complementary RNA targets, thereby influencing RNA processing or translation, primarily through RNase H-mediated degradation. Over the past decade, significant advances in chemical modifications and delivery strategies have led to a notable increase in the number of ASO-based therapies that have reached the market. Despite this progress, several challenges persist, including poor stability in biological fluids, limited cellular uptake, and safety concerns related to off-target effects and immunogenicity. This review provides a comprehensive overview of the mechanisms of action of ASOs, their pharmacological applications, current market status, and clinical progress. Special attention is given to evaluating in vitro and in vivo ASO stability using nanotechnology-based delivery approaches to improve pharmacokinetics/ pharmacodynamics and structural modifications to enhance therapeutic potential. Additionally, we discuss the associated adverse effects and propose strategies to mitigate them.

Lurasidone hydrochloride has limited water solubility and undergoes considerable first-pass metabolism, resulting in reduced oral bioavailability (<20 %). Encapsulating LRD into nano-carrier systems is an excellent approach to improve solubility and provide advantages such as targeted and sustained delivery, addressing limitations. The study focused on developing a straightforward, sensitive, and environmentally friendly HPLC analytical method for quantifying LRD in nanoformulations. Utilizing an analytical quality-by-design approach, an HPLC-based analytical method was developed using a C18 column and validated in accordance with ICH Q2(R1) guidelines. The mobile phase comprises an ammonium acetate buffer (30 mM) at pH 3.5, methanol, and acetonitrile in a ratio of 14:68:18, with an optimized flow rate of 0.82 mL/min. All analyses were conducted with a UV detector at 230 nm. A forced degradation study was conducted to assess the stability of LRD under various stress conditions. The optimized method demonstrated excellent linearity within the 0.5-4.0 mu g/mL concentration range. The LOD and LOQ values of 40.48 and 122.68 ng/mL reflect the method's high sensitivity. The results of forced degradation indicated the stability of LRD under various conditions. Furthermore, the results from multiple greenness-assessment tools, including GAPI, complex-GAPI, AGREE, and BAGI, validate the greenness and practical applicability of the improved technique.

Myopathies, joint impairment, muscle spasm, and torn muscles cause an excessive amount of musculoskeletal inflammation, which ultimately causes muscular soreness and stiffness, leading to difficulty in mobility. NSAIDs can suppress the COX enzyme, crucial for converting arachidonic acid into prostaglandin-E2. Oxidative burden increases during impaired health conditions, alleviating and prolonging the inflammatory phase and pain sensation. DA is a widely accepted NSAID that functions as a non-specific inhibitor of COX and is reported to have antioxidant properties. However, it has low solubility and severe adverse effects when used at high doses over a long-term therapy. Thus, the objective of this study is to develop a DA-loaded transferosomal gel with promising anti-inflammatory and antioxidant activity that resembles the commercially available gel, with improved solubility, decreasing the higher dose regimen, minimize potential side effects, and facilitating muscular pain relief over a long period of time. Transferosomes were prepared with a modified thin film hydration technique. The optimized formulation attained the desired particle size, PDI, and zeta potential with high entrapment. The transferosomal gel was investigated for physical characterization, in vitro diffusion, ex vivo permeation, and cellular studies. A cumulative drug release of 92.89 ± 4.21

INTRODUCTION:Globally, breast cancer (BC) affects a greater number of women than any other kind of cancer, and it is the second leading cause of death after lung cancer. The current standard of care for cancer treatment is the surgical excision of the malignant tumor followed by adjuvant therapy with chemotherapy or radiation. Regrettably, the side effects of radiation and chemotherapy frequently cause harm to healthy tissues and organs, hence limiting the effectiveness of these treatments in addressing BC. Recently, various nanoparticles (NPs) have been discovered and manufactured with the capacity to selectively target cancerous cells while minimizing harm to normal cells or organs. As a result, the utilization of NPs-mediated targeted drug delivery systems (DDS) has emerged as a promising method for treating BC. OBJECTIVE:The primary aim of this review was to provide a concise overview of the function of different nanoparticles in the specific delivery of anticancer medications to eradicate breast cancer. METHODS:The present review paper performed a literature inspection using several search engines such as PubMed, Google Scholar, and Science Direct. RESULTS:In addition to their ability to selectively target tumor cells and minimize side effects, nanoparticles (NPs) possess other distinctive characteristics that make them highly desirable for cancer treatment. These include low toxicity, excellent compatibility, ease of preparation, high photoluminescence for in vivo bioimaging, and the capacity to efficiently load drugs due to their adjustable surface functionalities. CONCLUSION:This study provides a comprehensive examination of recent therapeutic studies that utilize various nanoparticle-mediated drug delivery systems as alternatives to established therapy techniques for breast cancer. This study will elucidate the importance of nanoparticle-mediated drug delivery systems (DDS) and provide a roadmap for identifying the optimal approach for future targeted drug delivery, specifically for the treatment of breast cancer.

Fungal skin infections often require prolonged therapy; however, conventional ciclopirox olamine (CO) formulations exhibit poor penetration and limited skin retention, reducing efficacy. This study aimed to develop a CO-loaded cubosomal hydrogel patch to enhance skin permeation, retention, and antifungal activity. Cubosomes were prepared using glyceryl monooleate and Kolliphor 407 by the top-down technique and optimized through a 23 factorial design for particle size and entrapment efficiency. The optimized cubosomal dispersion was incorporated into a hydrogel patch containing sodium alginate and hydroxypropyl methylcellulose by solvent casting. Formulations were evaluated for physicochemical properties, drug release, permeation, antifungal activity, histocompatibility, and stability. Optimized cubosomes showed nanosized particles with high entrapment efficiency and stable morphology. FTIR and XRD confirmed successful encapsulation without interaction, while SEM revealed a porous surface enabling controlled diffusion. The optimized patch exhibited sustained release (97.82 % over 48 h), enhanced skin permeation (96.41 %), and stronger antifungal activity against Candida albicans compared to marketed cream. It demonstrated suitable mechanical strength, pH compatibility, biocompatibility, and three-month stability.

Introduction: The azole class of antifungal drugs is widely used to treat skin infec-tions. However, they have low local bioavailability due to poor penetration through the physio-logical barrier of the skin. To resolve this issue, an attempt has been made to fabricate Ebercona-zole nitrate cubosomes, which are added into a gel base for topical delivery. Methods: Cubosomes are prepared using the emulsification method, and the Box Behnken de-sign was applied for statistical analyses of selected formulation variables and optimization of the prepared batches. The optimized batches are subjected to various evaluation tests. Further, the hydrogel is prepared by incorporating an optimized batch of cubosomes (SO) and evaluated for in vitro diffusion, ex vivo permeation study, and stability studies. Results: The particle size, polydispersity index, zeta potential, and entrapment efficiency of SO are found to be 116.9 - 156.6 nm, 0.158 - 0.255, 2.69 - 5.04 mV, and 94.01 - 95.33 %, respec-tively. The morphological analysis demonstrated that the vesicles are well isolated from one an-other and have a uniform size. The powder X-ray diffraction pattern depicted the conversion of the crystalline nature of the drug to an amorphous form. Fourier Transform Infrared Spectrosco-py and Differential Scanning Calorimetry indicated absolute encapsulation of the drug inside the vesicles. The formulated hydrogel (EBN-CuG) showed desirable pH (6.9-7.4), viscosity (9000-12000 cps), spreadability (4.5-5.5 cm), and swelling (0.5-0.6 g/g). discussion: The in vitro drug release data indicated 77.75 % release at the end of 8h. Ex vivo skin permeation showed 94% permeation of the drug from the Wistar albino rat skin, which is higher than the conventional gel and marketed product. Discussion: The in vitro drug release data indicated 77.75 % release at the end of 8h. Ex vivo skin permeation showed 94% permeation of the drug through the Wistar albino rat skin, which is higher than the conventional gel and the marketed product. Conclusion: Considering all the results, it was proven that the drug from the cubosomal gel has higher permeation through the physiological barrier of the skin, and hence, it can be considered an effective alternative for treating fungal infections topically.

A novel reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and optimized for the estimation of Mangiferin (MGF) by employing a Quality by Design (QbD) approach. Preliminary method screening was done by the Taguchi OA, followed by using a Box-Behnken Design (BBD), enabling systematic evaluation of critical factors with a reduced number of experimental runs. The model efficiently established significant correlations between selected variables and analytical responses, thereby enhancing the method's robustness and reliability. Chromatographic separation was achieved on a Hyperclone C18 column (4.6 × 250 mm, 5 μm) using an isocratic mobile phase consisting of phosphate buffer (pH 3.2) and acetonitrile (30%) + methanol (70%) in a 78:22% v/v ratio, at a flow rate of 1.0 mL/min. Detection was performed using a photodiode array detector at 258 nm. The method was validated in accordance with ICH Q2-(R2) guidelines. Validation parameters, including system suitability, linearity, accuracy, precision, robustness, sensitivity, and solution stability, were found within acceptable limits. The proposed method was successfully applied for the analysis of the stability study of MGF and to analyze the release kinetics of MGF SLNs, formulated via high-pressure homogenization and the sonication technique. The results confirm the applicability of the developed RP-HPLC method for routine quality control of combination nanocarrier systems.

Biochanin A (BCA) is a natural isoflavone belonging to the BCS class II exhibiting low solubility and having anti-cancer, anti-inflammatory, neuroprotective, and anti-oxidant activity. This study explores the in vitro release and ex vivo permeation enhancement of BCA by formulating a self-nanoemulsifying drug delivery system (SNEDDS) utilising the Quality by Design (QbD) approach. A QbD-based design strategy was employed to optimize the BCA-loaded SNEDDS. The Quality target product profiles (QTPPs) and critical quality attributes (CQAs) were set to get the desired product profile and to build a quality product, while critical material attributes (CMAs) and critical process parameters (CPPs) are material and process controls that were controlled to achieve them. Oil (rice bran oil), surfactant (Tween 80), and co-surfactant (PEG 400) were selected based on solubility study and emulsification ability. SNEDDS were prepared by using the spontaneous emulsification method and a custom design in JMP® (version 18) was utilized to optimize BCA-loaded SNEDDS formulations. The formulations were characterized for globule size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), self-emulsification,

Advanced drug delivery systems are superior alternatives for antihypertensive drugs with poor solubility and bioavailability. Cubosomes are lipid-based nanostructured particles with a cubic internal phase that function as drug carriers, improving solubility and permeability through skin. This study involves the development and evaluation of cilnidipine cubosomal nanogel patches (CLD CB NGP) for transdermal drug delivery. The CLD-loaded cubosomes were prepared by a top-down approach, optimized by a Box-Behnken design, and evaluated for particle size, encapsulation efficiency, zeta potential, and morphological structure. They were then developed into a polymeric nanogel patch using hydrophilic polymers. The transdermal patches were evaluated for surface morphology, swelling, bioadhesiveness, in vitro drug release, and ex vivo permeation through excised rat skin. The CLD cubosomes were polyangular nanoparticles (430 nm), with high drug entrapment efficiency (80.8

Transdermal drug delivery systems (TDDS) offer a noninvasive alternative to conventional routes but are limited by poor drug permeability. Glycerospanlastics, owing to their deformability and enhanced penetration ability, can overcome these challenges. This study explores the design and development of Benidipine HCl (BND) glycerospanlastic polymeric microneedles to improve transdermal drug delivery. Glycerospanlastics were prepared using a surfactant-based approach and incorporated into polymeric microneedles. The formulations were characterized for particle size, zeta potential, encapsulation efficiency, morphology, and in vitro drug release. The microneedles were evaluated for morphology, mechanical strength, skin penetration, and in vitro drug release. The optimized glycerospanlastic formulation exhibited a bi-layered structure, high drug entrapment (87.9%), nanoscale size (656.5 nm), and sustained release properties. The polymeric microneedles demonstrated sufficient mechanical strength for skin insertion with a drug loading of 87.89%, sustained drug release over 33 hours and a permeation enhancement of 3.8-fold, ensuring efficient transdermal drug delivery. The integration of nanovesicular glycerospanlastics with polymeric microneedles provides a novel strategy for improving transdermal drug delivery, particularly for poorly water-soluble drugs. This study highlights the potential of glycerospanlastic polymeric microneedles as a patient-friendly and efficient alternative for drug administration.