Search Results (406)

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Androgenetic alopecia (AGA) is the most prevalent form of alopecia areata. Traditional treatment options, including minoxidil, finasteride, and hair transplantation, have their limitations, such as skin irritation, systemic side effects, invasiveness, and high costs. The transdermal drug delivery system (TDDS) offers an innovative approach for treating AGA by administering medications through the skin to achieve localized and efficient delivery while overcoming the skin barrier. This review systematically explores the application of TDDS in AGA treatment, highlighting emerging technologies such as microneedles (MNs), liposomes, ionic liquids (ILs), nanostructured lipid carriers (NLCs), and transporters (TFs). It analyzes the underlying mechanisms that enhance drug penetration through hair follicles. Finally, this review presents a forward-looking perspective on the future use of TDDS in the management of AGA, aiming to provide insights and references for designing effective transdermal drug delivery systems for this condition. Full article

The increasing demand for sustainable disease management in aquaculture has intensified interest in plant-based therapeutics. This study evaluated the formulation and efficacy of andrographolide-loaded nanostructured lipid carriers (AND-NLCs) in Nile tilapia (Oreochromis niloticus) challenged with Streptococcus agalactiae ENC06. AND-NLCs were prepared by the phase-inversion technique and characterized by dynamic light scattering, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and in vitro release profiling. Antibacterial activity was assessed by measuring inhibition zone diameters, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Growth performance, feed utilization, hepatosomatic index (HSI), and disease resistance were evaluated over a 60-day feeding trial. The AND-NLCs exhibited an optimal particle size (189.6 nm), high encapsulation efficiency (90.58%), sustained release, and structural stability. Compared to the free AND and control group, AND-NLC supplementation significantly improved growth, feed efficiency, HSI, and positive allometric growth. It also enhanced survival (73.3%) and relative percent survival (RPS = 65.6%) following S. agalactiae ENC06 infection. Antibacterial efficacy and physiological responses showed positive correlations with nanoparticle characteristics. These findings suggest that AND-NLCs enhance bioavailability and therapeutic efficacy, supporting their potential as a functional dietary additive to promote growth and improve disease resistance in tilapia aquaculture. Full article

Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into liposomes (Lipo) or nanostructured lipid carriers (NLCs) and characterized in terms of size, entrapment efficiency, morphology, and effects on two cancer cell lines (melanoma B16-F10 and breast carcinoma Walker 256 cells). Methods and Results: While liposomal formulations containing acidic doxorubicin displayed IC₅₀ values ranging from 1.33 to 0.37 µM, NLC-based formulations, particularly NLC-Doxo@Ac, demonstrated enhanced cytotoxicity with IC₅₀ values as low as 0.58 µM. Neutral Doxorubicin demonstrated lower cytotoxicity in both the nanoformulations and cell lines. Differences were also observed in their internalization patterns, cell-cycle impact, and apoptotic/necrotic effects. Compared to liposomes, NLCs exhibited distinct internalization patterns and induced stronger cell-cycle arrest and necrosis, especially in melanoma cells. Notably, NLC-Doxo@Ac outperformed liposomal counterparts in melanoma cells, while liposomal formulations showed slightly higher efficacy in Walker cells. Early and late apoptosis were more pronounced in Walker cells, whereas necrosis was more prominent in melanoma B16-F10 cells, particularly with the nanolipid formulations. Conclusions: These results correlated positively with cell-cycle measurements, highlighting the potential of NLCs as an alternative to liposomes for the delivery of neutral or acidic doxorubicin, particularly in tumor types that respond poorly to conventional formulations. Full article

Fucoxanthin, a marine-derived carotenoid primarily sourced from algae and microalgae, holds significant potential for pharmaceutical and nutraceutical applications. However, its highly unsaturated structure presents critical challenges, including structural instability, poor aqueous solubility, and limited bioavailability. These restrict its application despite its abundant natural availability. Recently, various controlled-release nanotechnologies have been applied to improve the properties of fucoxanthin formulations. In this review, we systematically summarized the bioactivities of fucoxanthin and highlighted recent advancements in controlled-release systems designed to address the limitations. These controlled-release systems mainly use natural or synthetic organic materials and are employed to develop various formulations, including emulsions, nanoparticles, nanofibers, and nanostructured lipid carriers. In addition, the emerging bioinspired drug delivery systems, particularly extracellular vesicles and cell-membrane-derived biomimetic systems, have gained prominence for their immunocompatibility and ability to penetrate physiological barriers, which is regarded as superior encapsulation vesicles for fucoxanthin. Focusing on innovations, we discussed the state-of-the-art delivery systems for fucoxanthin encapsulation and emphasized their roles in improving biosafety, enhancing bioavailability, preserving bioactivity, and optimizing therapeutic performance across various disease models. These insights will provide promising guidance for engineering controlled-release platforms and will aim to unlock fucoxanthin’s full potential in drug development and dietary supplement formulations. Full article

The advancement of efficient drug delivery systems continues to pose a significant problem in pharmaceutical sciences, especially for compounds with limited water solubility. Lipid-based systems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have emerged as viable options owing to their biocompatibility, capability to safeguard labile chemicals, and potential for prolonged release. Nonetheless, the encapsulation efficiency (EE) and release dynamics of these carriers can be enhanced by including cyclodextrins (CDs)—cyclic oligosaccharides recognized for their ability to form inclusion complexes with hydrophobic compounds. This article offers an extensive analysis of CD-modified SLNs and NLCs as multifunctional drug delivery systems. The article analyses the fundamental principles of these systems, highlighting the pre-complexation of the drug with cyclodextrins before lipid incorporation, co-encapsulation techniques, and surface adsorption after formulation. Attention is concentrated on the physicochemical interactions between cyclodextrins and lipid matrices, which influence essential factors such as particle size, encapsulation efficiency, and colloidal stability. The review includes characterization techniques, such as particle size analysis, zeta potential measurement, drug release studies, and Fourier-transform infrared spectroscopy (FT-IR)/Nuclear Magnetic Resonance (NMR) analyses. The study highlights the application of these systems across many routes of administration, including oral, topical, and mucosal, illustrating their adaptability and potential for targeted delivery. The review outlines current formulation challenges, including stability issues, drug leakage, and scalability concerns, and proposes solutions through advanced approaches, such as stimuli-responsive release mechanisms and computer modeling for system optimization. The study emphasizes the importance of regulatory aspects and outlines future directions in the development of CD-lipid hybrid nanocarriers, showcasing its potential to revolutionize the delivery of poorly soluble drugs. Full article

Developments of nanostructured materials have a significant impact in various areas, such as energy technology and biomedical use. Examples include solar cells, energy management, environmental control, bioprobes, tissue engineering, biological marking, cancer diagnosis, therapy, and drug delivery. Currently, researchers are designing multifunctional nanodrugs that combine in vivo imaging (using fluorescent nanomaterials) with targeted drug delivery, aiming to maximize therapeutic efficacy while minimizing toxicity. These fascinating nanoscale “magic bullets” should be available in the near future. Inorganic nanovehicles are flexible carriers to deliver drugs to their biological targets. Most commonly, mesoporous nanostructured silica, carbon nanotubes, gold, and iron oxide nanoparticles have been thoroughly studied in recent years. Opposite to polymeric and lipid nanostructured materials, inorganic nanomaterial drug carriers are unique because they have shown astonishing theranostic (therapy and diagnostics) effects, expressing an undeniable part of future use in medicine. This review summarizes research from development to the most recent discoveries in the field of nanostructured materials and their applications in drug delivery, including promising metal-based complexes, platinum, palladium, ruthenium, titanium, and tin, to tumor cells and possible use in theranostics. Full article

Background/Objectives: Clofazimine (CFZ) is a versatile antimicrobial active against several bacterial species, although its reduced aqueous solubility and the occurrence of side effects limit its use. Nanostructured lipid carriers (NLCs) constitute an interesting approach to increase drug bioavailability and safety. However, the development of nanoparticle-based formulations is challenging. In the present work, a combination of smart pharmaceutical technology approaches was proposed to develop CFZ-loaded NLCs, taking advantage of previous knowledge on NLCs screening. Methods: A design space previously established using Artificial Intelligence (AI) tools was applied to develop CFZ-loaded NLC formulations. After formulation characterization, Neurofuzzy Logic (NFL) and in silico docking simulations were employed to enhance the understanding of lipid nanocarriers. Then, the performance of formulations designed following NFL guidelines was characterized in terms of biocompatibility, using murine fibroblasts, and antimicrobial activity against several strains of Staphylococcus aureus. Results: The followed approach enabled CFZ-loaded NLC formulations with optimal properties, including small size and high antimicrobial payload. NFL was useful to investigate the existing interactions between NLC components and homogenization conditions, that influence CFZ-loaded NLCs’ final properties. Also, in silico docking simulations were successfully applied to examine interactions and affinity between the drug and the lipid matrix components. Finally, the designed CFZ-loaded formulations demonstrated suitable biocompatibility, together with antimicrobial activity. Conclusions: The implementation of smart strategies during nanoparticle-based therapeutics development, such as those described in this manuscript, would enable the more efficient design of new systems for suitable antimicrobial delivery. Full article

Meloxicam is a promising non-steroidal anti-inflammatory drug (NSAID) for acute and chronic pain prevention and treatment. Due to its poor water solubility, the clinical use of meloxicam is limited. In addition, for transdermal applications, the impermeability of the skin makes it difficult to conceive an appropriate NSAID-based delivery system that can penetrate through the skin barrier. Hydrophilic/hydrophobic gels, designed as transdermal drug delivery systems, can considerably improve other drug administration types (such as oral or intravenous), avoiding or limiting the side effects. The main purpose of this paper is to present some physicochemical and pharmaceutical considerations about meloxicam and to review the most important research concerning the gels used for the transdermal delivery of meloxicam. Thus, smart polymeric networks, semi-solid systems (lipogels, emulgels), β-cyclodextrin-based gels, liposomes (ethosomes, niosomes, flexosomes, transferosomes, menthosomes, invasomes), and nanostructured lipid carriers, with analgesic and anti-inflammatory activity, are discussed. The key objective of this study was to highlight various gel formulations with enhanced properties, which could be used in a minimally invasive manner for the sustained administration of meloxicam. Full article

Background/Objectives: Rifampicin is a typical antibiotic used for the treatment of Staphylococcus aureus (S. aureus) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing bacterial resistance. Nanostructured lipid carriers (NLCs) offer a promising strategy to improve drug solubility, stability, and antimicrobial performance. Methods: In this study, rifampicin-loaded NLC (NLC-RIF) was developed using a hot homogenization with a low energy method and characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, colloidal stability, and drug loading. Results: In vitro release studies under sink conditions demonstrated a biphasic release pattern, best described by the Korsmeyer–Peppas model, suggesting a combination of diffusion and matrix erosion mechanisms. Antimicrobial activity against S. aureus revealed a substantial increase in potency for NLC-RIF, with an IC₅₀ of 0.46 ng/mL, approximately threefold lower than that of free rifampicin. Cytotoxicity assays in HepG2 cells confirmed over 90% cell viability across all tested concentrations. Conclusions: These findings highlight the potential of NLC-RIF as a biocompatible and effective nanocarrier system for enhancing rifampicin delivery and antibacterial activity. Full article

Background/Objectives: Difenoconazole (DFC) is a broad-spectrum fungicide. However, its application is limited due to poor aqueous solubility. Drugs with low solubility can be better absorbed using nanostructured lipid carriers (NLCs). Hence, the application of DFC in an NLC delivery system is proposed. Methods: Difenoconazole-loaded nanostructured lipid carriers (DFC-NLCs) with different solid–liquid lipid ratios were prepared by solvent diffusion method. Key physicochemical parameters, including particle diameter, surface charge (zeta potential), drug encapsulation efficiency, and morphological characteristics, were systematically characterized. Using Rhizoctonia solani (R. solani) as the model strain, inhibitory efficiency of DFC-NLC dispersion was compared with that of commercial dosage forms, such as 25% DFC emulsifiable concentrate (DFC-EC) and 40% DFC suspension concentrate (DFC-SC). Additionally, uptakes of DFC-NLC dispersions in R. solani were further observed by fluorescence probe technology. The safety profiles of DFC-NLCs and commercial dosage forms were evaluated using zebrafish as the model organism. Acute toxicity studies were conducted to determine the maximum non-lethal concentration (MNLC) and 10% lethal concentration (LC₁₀). Developmental toxicity studies were performed to observe toxic phenotypes. Results: DFC-NLC dispersions were in the nanometer range (≈200 nm) with high zeta potential, spherical in shape with encapsulation efficiency 69.1 ± 1.8%~95.0 ± 2.6%, and drug loading 7.1 ± 0.3%~9.7 ± 0.6% determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Compared with commercial dosage forms, the antifungal effect of the DFC-NLC on R. solani was significantly improved in in vitro antibacterial experiments (p < 0.05). The 50% effective concentration (EC₅₀) values were 0.107 mg·L⁻¹ (DFC-NLC), 0.211 mg·L⁻¹ (DFC-EC), and 0.321 mg·L⁻¹ (DFC-SC), respectively. The uptakes of FITC-labeled DFC-NLC demonstrated that an NLC was appropriate to deliver DFC into pathogen to enhance the target effect. In safety assessment studies, DFC-NLCs exhibited a superior safety profile compared with commercial formulations (p < 0.05). Conclusions: This study investigates the feasibility of NLCs as delivery systems for poorly water-soluble fungicides, demonstrating their ability to enhance antifungal efficacy and reduce environmental risks. Full article

Background/Objectives: Continuous manufacturing is gaining importance in the nanopharmaceutical field, offering improved process efficiency and product consistency. To fully leverage its potential, the integration of Process Analytical Technology (PAT) tools is essential for real-time quality control and robust process monitoring. Among the critical quality attributes (CQAs) of nanosystems, particle size plays a key role in ensuring product consistency and performance. However, real-time size monitoring remains challenging due to complex process dynamics and nanosystem heterogeneity. Methods: This study evaluates the applicability of conventional Dynamic Light Scattering (DLS) and spatially resolved DLS (SR-DLS) using the NanoFlowSizer (NFS) as PAT tools in a temperature-regulated top-down nano-production line. Various lipid-based nanosystems, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsions (NEs), were investigated. To ensure reliable implementation, key factors such as sample dilution, viscosity, focus position, measurement angle and temperature effects were systematically assessed for offline and at-line DLS using the Litesizer 500, as well as for offline, inline, and online SR-DLS using the NFS. Results: Offline screening confirmed that selecting the appropriate dilution medium and rate ensures measurement reliability. At-line methods provided an efficient alternative by enabling rapid final product control with minimal manual intervention. Inline and online monitoring further enhanced process efficiency by enabling real-time tracking of size, reducing waste, and allowing immediate process adjustments. Conclusions: This study demonstrates that integrating offline, at-line, in-line, and online DLS techniques allows for comprehensive product monitoring throughout the entire production line. This approach ensures a streamlined process, enables real-time adjustments, and facilitates reliable quality control after production and during storage. Full article

Objectives: This study aimed to develop and evaluate nanostructured lipid carriers (NLCs) loaded with meloxicam (Melox) and a therapeutic antibacterial and anti-inflammatory liquid lipid, clove oil (CO) for periodontitis treatment, a complex inflammatory condition necessitating advanced drug delivery systems. The NLC–Melox formulation was integrated into three hydrogels, hypromellose (HPMC), zinc hyaluronate (ZnHA), and sodium hyaluronate (NaHA), to conduct a comparative analysis focusing on enhanced localized drug delivery, improved mucoadhesion, prolonged retention, and significant therapeutic outcomes. Methods: NLC–Melox was prepared by homogenization and characterized by dynamic light scattering (DLS). Subsequently, NLC–Melox-loaded gels were subjected to transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Raman spectroscopy, and rheological analysis. In vitro drug release, anti-inflammatory activity (BSA denaturation assay), and antibacterial efficacy (MIC, MBC) were investigated to assess therapeutic potential. Results: DLS revealed a particle size of 183 nm with a polydispersity index of 0.26, indicating homogeneity. TEM confirmed consistent morphology and uniform nanoparticle distribution. DSC and XRD demonstrated the amorphous nature of Melox, enhancing solubility and stability. Spectroscopy confirmed no chemical interactions between components. Rheological studies identified ZnHA as the most mucoadhesive and structurally stable gel. In vitro release studies showed sustained drug release over 24 h. Melox and CO-loaded formulations demonstrated significant anti-inflammatory activity and notable antibacterial efficacy due to the antibacterial oil. Conclusions: The study highlighted the potential of NLC-based mucoadhesive hydrogels as an effective strategy for periodontitis treatment. The formulation offered improved drug solubility, therapeutic efficacy, mucoadhesivity, and prolonged delivery, making it a promising candidate for localized therapy. Full article

In recent decades, nose-to-brain drug delivery has shown effectiveness in treating many central nervous system diseases. Intranasally administered drugs can be delivered to the brain through the olfactory and trigeminal pathways that bypass the blood–brain barrier. However, nose-to-brain drug delivery is challenging due to the inadequate nasal mucosa absorption of drugs and the short retention time of the intranasal formulations. These problems can be minimized through the use of nano-drug delivery systems, such as micelles, polymeric nanoparticles, nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers. They can enhance the drug’s bioavailability in the brain via increases in drug solubility, permeation, and stability. Nose-to-brain nano-drug delivery systems have been evaluated in vivo by a number of research groups. This review aims to provide an overview of nose-to-brain delivery and recent advances in the development of nano-drug delivery systems for delivering drugs from the nose to the brain to improve the treatment of some central nervous system diseases. Full article

Background/Objectives: The aim of the present study was to develop nanostructured lipid carrier (NLC)-filled hydrogel beads for the delivery of curcumin in functional foods. Methods: Curcumin-loaded NLC-filled hydrogel beads based on calcium alginate were developed using the extrusion method. Various preparation parameters, physicochemical characteristics, gastrointestinal fates, and antioxidant bioactivities were studied to confirm the feasibility of this delivery system. Results: Curcumin-loaded NLCs were successfully filled into hydrogel beads with an encapsulation efficiency above 80%. The stability test displayed that the stability of curcumin encapsulated within NLCs was further enhanced when the NLCs were filled into beads. During in vitro digestion, the lipolysis rate of the lipid matrix and the release rate of curcumin encapsulated in NLCs were adjusted by the hydrogel beads. The ex vivo intestinal permeation study indicated that the intestinal permeation of curcumin from the digestion products of curcumin-loaded NLC-hydrogel beads, prepared with appropriate alginate concentrations (0.5% and 1%), was significantly enhanced compared to that of curcumin-loaded NLCs. Furthermore, the digestion products of curcumin-loaded NLC-hydrogel beads (1% alginate) exhibited significantly enhanced antioxidant bioactivity compared to those of curcumin-loaded NLCs. Conclusions: This study demonstrated that NLC-hydrogel beads might be a promising delivery system for hydrophobic bioactive compounds in functional food systems. Full article