Search Results (406)

Liposomes (LPs) represent one of the most effective nanoscale platforms for drug delivery in cancer therapy due to their favorable pharmacokinetic and various body tissue compatibility profiles. Building on recent findings showing that carbon dots derived from N-hydroxyphthalimide (CDs-NHF) possess intrinsic antitumor activity, herein, we investigate the possibility of preparing complex nano-platforms composed of LPs encapsulating CDs-NHF and/or doxorubicin (DOX) for breast and lung cancer. Various LP formulations were prepared and characterized using Cryo-TEM and Cryo-SEM for morphological analysis, while zeta potential and fluorescence assessments confirmed their stability and optical properties. Cellular effects were evaluated through immunofluorescence microscopy and proliferation assays. LPs-CDs-NHF significantly reduced cancer cell viability at lower concentrations compared to free CDs-NHF, and this effect was further amplified when combined with doxorubicin. Mechanistically, the liposomal formulations downregulated key signaling molecules including pAKT, pmTOR, and pERK, indicating the disruption of cancer-related pathways. These findings suggest that LPs containing CDs-NHF, either alone or in combination with DOX, exhibit synergistic antitumor activity and hold strong promise as multifunctional nanocarriers for future oncological applications. Full article

Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet research on selenium products prepared using exosomes remains limited. To address this gap, we utilized Cyperus bean ELNs to deliver SeNPs, investigated three preparation methods for SeNPs-ELNs, identified the optimal approach, and performed characterization studies. Notably, all three methods successfully loaded SeNPs. Ultrasonic cell fragmentation is the optimal approach, achieving significant increases in selenium loading (5.59 ± 0.167 ng/μg), enlargement of particle size (431.17 ± 10.78 nm), and reduced absolute zeta potential (−4.1 ± 0.43 mV). Moreover, both exosome formulations demonstrated enhanced stability against aggregation during storage at 4 °C, while their stability varied with pH conditions. In vitro digestibility tests showed greater stability of SeNP-ELNs in digestive fluids compared to ELNs alone. Additionally, neither ELNs nor SeNP-ELNs exhibited cytotoxicity toward LO₂ cells, and the relative erythrocyte hemolysis remained below 5% at protein concentrations of 2.5, 7.5, 15, 30, and 60 μg/mL. Overall, ultrasonic cell fragmentation effectively loaded plant-derived exosomes with nano-selenium at high capacity, presenting new opportunities for their use as functional components in food and pharmaceutical applications. Full article

Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of lipid metabolism, making its agonists valuable therapeutic targets for various diseases, including chronic peripheral neuropathy. Existing PPARα agonists face limitations such as poor selectivity, sub-optimal bioavailability, and safety concerns. We previously demonstrated that A190, a novel, potent, and selective PPARα agonist, effectively alleviates chemotherapy-induced peripheral neuropathy and CFA-induced inflammatory pain as a non-opioid therapeutic agent. However, A190 alone has solubility and permeability issues that limits its oral delivery. To overcome this challenge, in this study, four new-generation ester prodrugs of A190; A190-PD-9 (methyl ester), A190-PD-14 (ethyl ester), A190-PD-154 (isopropyl ester), and A190-PD-60 (cyclic carbonate) were synthesized and evaluated for their enzymatic bioconversion and chemical stability. The lead candidate, A190-PD-60, was further formulated as a microemulsion (A190-PD-60-ME) and optimized via Box–Behnken design. A190-PD-60-ME featured nano-sized droplets (~120 nm), low polydispersity (PDI < 0.3), and high drug loading (>90%) with significant improvement in artificial membrane permeability. Crucially, pharmacokinetic evaluation in rats demonstrated that A190-PD-60-ME reached a 16.6-fold higher Cmax (439 ng/mL) and a 5.9-fold increase in relative oral bioavailability compared with an A190-PD-60 dispersion. These findings support the combined prodrug-microemulsion approach as a promising strategy to overcome oral bioavailability challenges and advance PPARα-targeted therapies. Full article

Wound healing is a complex biological process that involves the regulation of reactive oxygen species (ROS), which play a critical role in cellular signaling and tissue repair. While the dual nature of ROS means that maintaining controlled levels is essential for effective wound healing, excessive ROS production can hinder the recovery process. Bioactive compounds represent promising therapeutic candidates enriched with polyphenols, which are known for their high therapeutic properties and minimal adverse effects, and are thus highlighted as promising therapeutic candidates for wound healing due to their antioxidant properties. However, their clinical application is often limited due to challenges such as poor solubility and low bioavailability. To overcome this, the encapsulation of these compounds into nanocarriers has been proposed, which enhances their stability, facilitates targeted delivery, and allows for controlled release. The present review highlights emerging innovations in nanomedicine-based drug delivery of natural antioxidants for precise modulation of ROS in wound healing. Moreover, the review elaborates briefly on various in vitro and in vivo studies that assessed the ROS levels using different fluorescent dyes. By modulating ROS levels and improving the local microenvironment at wound sites, these bioactive-nanomedicine formulations can significantly accelerate the healing process of wounds. The review concludes by advocating for further research into optimizing these nano-formulations to maximize their potential in clinical settings, thereby improving therapeutic strategies for wound care and regeneration. Full article

The mRNA vaccine has protected humans from the Coronavirus disease 2019 (COVID-19) and has taken the lead in reversing the epidemic efficiently. However, the Centre of Disease Control (CDC) reported and raised the alarm of allergic or acute inflammatory adverse reactions after vaccination with mRNA-LNP vaccines. Meanwhile, the US Food and Drug Administration (FDA) has added four black-box warnings in the instructions for mRNA-LNP vaccines. Numerous studies have proven that the observance of side effects after vaccination is indeed positively correlated to the level of anti-PEG antibodies (IgM or IgG), which are enhanced by PEGylated preparations like LNP vaccine and environmental exposure. After literature research and review in the past two decades, it was found that the many clinical trial failures (BIND-014, RB006 fell in phase II) of PEG modified delivery system or PEGylated drug were related to the high expression of anti-PEG IgM and IgG. In the background of shooting multiple mRNA-LNP vaccines in billions of people around the world in the past three years, the level of anti-PEG antibodies in the population may have significantly increased, which brings potential risks for PEG-modified drug development and clinical safety. This review summarizes the experience of using mRNA-LNP vaccines from the mechanism of the anti-PEG antibodies generation, detection methods, clinical failure cases of PEG-containing products, harm analysis of abuse of PEGylation, and alternatives. In light of the increasing prevalence of anti-PEG antibodies in the population and the need to avoid secondary injuries, this review article holds greater significance by offering insights for drug developers. It suggests avoiding the use of PEG excipients when designing PEGylated drugs or PEG-modified nano-formulations and provides references for strategies such as utilizing PEG-free or alternative excipients. Full article

The development of nanocarriers for drug delivery has drawn a lot of attention due to the possibility for tailored delivery to the ill region while preserving the neighboring healthy tissue. In medicine, delivering drugs safely and effectively has never been easy; therefore, the creation of surfactant-based vesicles (niosomes) to enhance medication delivery has gained attention in the past years. Niosomes (NIOs) are versatile drug delivery systems that facilitate applications varying from transdermal transport to targeted brain delivery. These self-assembling vesicular nano-carriers are formed by hydrating cholesterol, non-ionic surfactants, and other amphiphilic substances. The focus of the review is to report on the latest NIO-type formulations which also include biopolymers from the polysaccharide class, highlighting their role in the development of these drug delivery systems (DDSs). The NIO and polysaccharide types, together with the recent pharmaceutical applications such as ocular, oral, nose-to brain, pulmonary, cardiac, and transdermal drug delivery, are all thoroughly summarized in this review, which offers a comprehensive compendium of polysaccharide-based niosomal research to date. Lastly, this delivery system’s limits and prospects are also examined. Full article

The incidence of fungal infections is significantly rising, posing a challenge due to the limited class of antifungal drugs. There is a necessity to combat emerging resistant fungal infections by developing novel antifungal agents. This study aimed to evaluate the antifungal effects of lawsone (LAW), a natural component extracted from herbal medicine, and LAW-loaded mesoporous silica nanoparticles (LAW-MSNs) on growth, biofilm formation, and expression of ALS1 and EPA1 genes contributing to cell adhesion of Candida spp. Twenty C. albicans and twenty C. glabrata isolates, including ten fluconazole-resistant and ten fluconazole-susceptible isolates, were examined. The findings of the study indicated that LAW and LAW-MSNs inhibited Candida isolates growth at MIC range of 0.31–>5 µg/mL and significantly reduced biofilm formation in C. albicans and C. glabrata. Moreover, both LAW and LAW-MSNs downregulated the expression of the adhesion genes ALS1 and EPA1 in C. albicans and C. glabrata. Based on the obtained findings, LAW emerged as a promising antifungal candidate. However, the nano-formulation (LAW-MSNs) improved its antifungal properties. Full article

Protein-bound nano-injectable solutions represent a cutting-edge advancement in nanomedicine, offering a versatile platform for precise and controlled drug delivery. By leveraging the biocompatibility and functional versatility of proteins such as albumin, gelatin, and casein, these nano systems enhance drug solubility, prolong circulation time, and improve site-specific targeting, which are particularly beneficial in cancer and inflammatory diseases. This review provides a comprehensive overview of their formulation strategies, physicochemical characteristics, and biological behavior. Emphasis is placed on therapeutic applications, regulatory considerations, fabrication techniques, and the underlying mechanisms of drug–protein interactions. This review also highlights improved pharmacokinetics and reduced systemic toxicity, while also critically addressing challenges like immunogenicity, protein instability, and production scalability. Recent FDA-approved formulations and emerging innovations in precision medicine and theranostics underscore the transformative potential of protein-based nanosuspensions in next-generation drug delivery systems. Full article

Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs. Full article

Nasal drug delivery faces numerous challenges related to the ineffectiveness of most nasal formulations without a mucoadhesive nature, prolonging residence time on the nasal mucosa. Another challenge is the low administrable dosage strength, which can be solved via nano-encapsulation techniques, including the utilization of polymeric micelles. In this study, gellan gum–cellulose derivative complex in situ gelling matrices were formulated to test their effect on the colloidal characteristics of polymeric micelles, their respective rheological behavior, and nasal applicability. It has been proven that these complex matrices can form gels upon contact with nasal fluid without disrupting the micellar structure. Changes in the drug release and permeation profile have been shown in a concentration-dependent manner to hinder the burst-like drug release profile of polymeric micelles. Formulations show concentration- and composition-dependent mucoadhesive features under nasal conditions. Most of the hydrogels possess a soft gel characteristic, making them suitable for nasal administration. In conclusion, this descriptive study provides useful insights for conscious, nasal dosage form design. Full article

Background/Objectives: Proteolysis-targeting chimeras (PROTACs) have shown significant potential in the treatment of intractable diseases. However, their clinical applications are limited by poor water solubility and permeability. In this study, the cyclodextrin inclusion method was employed for the first time to prepare the PROTAC-CD complex with the aim of improving the dissolution of a PROTAC drug (LC001). Methods: Initially, sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was selected to improve the solubility of LC001. The polymer TPGS was screened based on the phase solubility method to enhance the efficiency of complexation and solubilization capacity, and its ratio with SBE-β-CD was optimized. The ternary complex was prepared by lyophilization with an SBE-β-CD/TPGS molar ratio of 1:0.03. Differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy results confirmed the formation of an amorphous complex. Fourier-transform infrared and molecular docking simulations indicated the formation of hydrogen bond interactions between components. Results: The results showed that the ternary complexes significantly improved the dissolution rate and release amount of LC001 in PBS (pH 6.8) and were unaffected by changes in gastric pH compared to the binary complexes and physical mixtures. The lack of crystal structure in the lyophilized particles and the formation of nano aggregates in solution may be the reasons for the improved dissolution of the ternary complex. Conclusions: In conclusion, the addition of TPGS to the LC001-SBE-β-CD binary system has a synergistic effect on improving the solubility and dissolution of LC001. This ternary complex is a promising formulation for enhancing the dissolution of LC001. Full article

Periodontitis is a prevalent oral condition worldwide. Azithromycin, a conventional lipophilic drug for periodontal treatment, often causes systemic side effects when administered orally. To address this, azithromycin-loaded nano-emulgels were developed using olive oil as a carrier within a xanthan gum aqueous gel phase. This oil-in-aqueous gel emulsion was actuated into a foam for localized drug delivery in gingival and periodontal disease. The solubility of azithromycin in various vehicles was tested, with olive oil showing the best solubility (0.347 mg/mL). Thermodynamic stability testing identified viable nano-formulations, with encapsulation efficiencies ranging from 98 to 100%. These formulations exhibited rapid drug release within 2–8 h. Muco-adhesion studies and ex vivo permeability tests on porcine buccal mucosa highlighted the beneficial properties of xanthan gum for local drug retention within the oral cavity. Antimicrobial efficiency was assessed using minimum inhibitory concentrations against various oral pathogens, where the formulation with equal surfactant and co-surfactant ratios showed the most potent antibacterial activity, ranging from 0.390 to 1.56 µg/mL. This was supported by the shear-thinning, muco-adhesive, and drug-retentive properties of the xanthan gel base. The study also examined the influence of the oil phase with xanthan gum gel on foam texture, rheology, and stability, demonstrating a promising prototype for periodontitis treatment. Full article

Curcumin (Cur) is one of the most studied natural polyphenolic compounds, with many pharmacological properties and a luminescent skeleton. Natural fluorescent molecules are peculiar tools in nanomedicine for bioimaging and sensing, and this review focuses on the photophysical properties and applications of Cur in these biomedical fields. The first part of the review opens with a description of the Cur chemical skeleton and its connection with the luminescent nature of this molecule. The 1,6-heptadiene-3,5-dionyl chain causes the involvement of Cur in a keto–enol tautomerism, which influences its solvatochromism. The polyphenolic nature of its skeleton justifies the Cur generation of singlet oxygen and ROS upon photoexcitation, and this is responsible for the photophysical processes that may be related to the photodynamic therapy (PDT) effects of Cur. In the second part of the review, bioimaging based on Cur derivatives is reviewed, with a deeper attention paid to the molecular diagnostic and nano-formulations in which Cur is involved, either as a drug or a source of fluorescence. Theragnostics is an innovative idea in medicine based on the integration of diagnosis and therapy with nanotechnology. The combination of diagnostics and therapy provides optimal and targeted treatment of the disease from its early stages. Curcumin has been involved in a series of nano-formulations exploiting its pharmacological and photophysical characteristics and overcoming its strong lipophilicity using biocompatible nanomaterials. In the third part of the review, modifications of the Cur skeleton were employed to synthesize probes that change their color in response to specific stimuli as a consequence of the trapping of specific molecules. Finally, the methodologies of sensing biothiols, anions, and cations by Cur are described, and the common features of such luminescent probes reveal how each modification of the skeleton can deeply influence its natural luminescence. Full article

Prostate cancer is the most common tumor in men in developed countries and it often responds poorly to conventional treatments. Monoclonal antibody (MoAb) therapy, for this pathology, has grown tremendously in the past decades, exploiting naked and conjugated antibodies to cytotoxic payloads to form antibody drug conjugates (ADCs). Several studies have been carried out conjugating biomolecules against prostate-specific membrane antigen (PSMA), highly expressed in this tumor, to cytotoxic drugs. Nano-based formulations show high potential in targeted drug delivery to enhance the bioavailability of drugs. Our research aimed to evaluate the feasibility of setting up a nanoparticle-based multimodal tool for targeted drug delivery, describing the step-by-step approach and to perform a first screening of these fluorescent PEGylated silica nanoparticles employed in selective cancer cell targeting and killing. These nanoparticles featured a core–shell structure to contemporarily conjugate the antibody and the cytotoxic payload monomethyl auristatin E (MMAE) using a step-by-step approach. We compared the cytotoxic effect of this multimodal nanotool near the antibody-MMAE and free MMAE. We found a lower cytotoxicity effect of the nanoparticle-based construct compared to free drugs, likely because of the preservation of the previously observed receptor-mediated endocytosis. Nanomedicine is confirmed as a powerful alternative to organic drug delivery systems, even if some aspects, such as drug loading efficacy, release, scalable manufacturing and long-term stability, need to be deepened. Full article

Cyclodextrins (CDs) enhance the solubility of poorly water-soluble drugs like ibuprofen (IBU), making them promising carriers for pulmonary drug delivery. This route lowers the required dose, minimizing side effects, which could be beneficial in treating cystic fibrosis. In this study, a nano-spray-drying technique was applied to prepare CD/IBU complexes using sulfobutylether-β-cyclodextrin (SBECD) or (2-Hydroxy-3-N,N,N-trimethylamino)propyl-beta-cyclodextrin chloride (QABCD) as carriers as well as mannitol (MAN) and leucine (LEU) as aerosolization excipients. Various investigation techniques were utilized to examine and characterize the samples, including a Master Sizer particle size analyzer, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). We applied in vitro Andersen Cascade Impactor measurements and in silico simulation analysis to determine the sample’s aerodynamic properties. We also performed in vitro dissolution and diffusion tests. Applying formulations with optimal aerodynamic properties, we achieved an improved ~50% fine particle fraction values based on the Andersen Cascade Impactor measurements. The in vitro dissolution and diffusion studies revealed rapid IBU release from the formulations; however, the QABCD-based sample exhibited reduced membrane diffusion compared to SBECD due to the formation of electrostatic interactions. Full article