Search Results (2,117)

The success of mRNA-based SARS-CoV-2 vaccines has been confirmed in both preclinical and clinical settings. However, the development of safe and efficient mRNA vaccine delivery platforms remains challenging. In this report, PBAE-G-B-SS-modified CaO₂ nanofibers and Au@OVA@Cu@Dendrobium huoshanense polysaccharides were employed to establish novel self-assembling polymeric micelles (CaO₂@Au@OVA@Cu@DHPs) capable of serving as both an adjuvant and a delivery system for mRNA vaccines. In vitro, CaO₂@Au@OVA@Cu@DHPs nanoparticles (NPs) were conducive to effective macrophage antigen uptake and efficient antigen processing. In vivo, P-CaO₂@Au@OVA@Cu@DHPs NP administration was associated with a reduction in the ovalbumin (OVA) release rate that was conducive to the sustained induction of long-term immunity and to the production of higher levels of different IgG subtypes, suggesting that these effects were attributable to enhanced antigen uptake by antigen-presenting cells. Overall, these present data highlight the promise of these P-CaO₂@Au@OVA@Cu@DHPs NPs as an effective and safe platform amenable to vaccine delivery through their ability to provide robust adjuvant activity and sustained antigen release capable of eliciting long-term immunological memory while potentiating humoral and cellular immune responses. Full article

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, S_mix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article

Background/Objectives: This study developed a targeted drug delivery nanoplatform for treating HER2-positive breast cancer. The nanoplatform encapsulated two hydrophobic anticancer agents, neratinib (NTB) and docetaxel (DTX), within nanoparticles (DTX+NTB−NP) functionalized for conjugation to trastuzumab to form trastuzumab-tagged nanoparticles (TRZ−NP). Trastuzumab is a HER2-specific monoclo-nal antibody that binds to HER2 receptors, blocking signal transduction and inducing an-tibody-dependent cellular cytotoxicity (ADCC). Upon receptor-mediated endocytosis, neratinib inhibits cytosolic HER2 signaling, while docetaxel disrupts mitotic cell division, collectively leading to tumor cell death. Methods: Nanoparticles were fabricated by the nanoprecipitation technique, followed by surface modification with a crosslinker and a targeting moiety. DTX+NTB−NP, TRZ−NP, and singly loaded nanoparticles (NTB−NP and DTX−NP) were characterized and their effects evaluated in HER2-positive cancer cell line and xenograft model. Results: In vitro antiproliferation assay in SKBR-3 cell line re-veals a dose and time-dependent cytotoxicity. There was no significant difference in cyto-toxicity observed between DTX+NTB−NP and its free form (DTX+NTB) [p = 0.9172], and between TRZ−NP and its free form (TRZ+DTX+NTB) [p = 0.6750]. However, TRZ−NP, at half the concentration of the singly loaded nanoparticles, significantly reduced the viabil-ity of SKBR-3 cells compared to pure trastuzumab (TRZ) [p < 0.001], NTB−NP [p = 0.0019], and DTX−NP [p = 0.0002]. In vivo evaluation in female athymic nude mice showed sig-nificant log relative tumor volume (%) reduction in groups treated with TRZ−NP and DTX+NTB−NP compared to PBS (phosphate-buffered saline) controls (p ≤ 0.001 and p ≤ 0.001), respectively. Notably, TRZ−NP demonstrated a statistically significant regression in the log relative tumor volume (%) compared to DTX+NTB−NP (p = 0.001). Conclusions: These findings underscore the therapeutic potential and suitability of these nanoplatforms for the precise and controlled targeting of HER2-positive tumors. This study is the first to synchronize the delivery of multiple agents-docetaxel, neratinib, and trastuzumab-within a nanoparticle system for treating HER2-positive tumors, offering a promising strategy to enhance treatment outcomes for HER2 positive breast cancer patients. Full article

Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating innovative therapeutic approaches. This scoping review summarizes experimental evidence on the anticancer activity of snake venom and its bioactive components against breast cancer, drawing from a variety of in vitro and in vivo studies. Aimed at critically evaluating the therapeutic potential and underlying mechanisms, this review consolidates findings on venoms from multiple snake species, including both crude preparations and purified proteins or peptides, revealing a diversity of mechanisms of action. Reported effects include induction of apoptosis, generation of reactive oxygen species, disruption of cell membrane integrity, inhibition of cell proliferation and metastasis, and modulation of oncogenic signaling pathways. In vivo findings further indicate tumor growth inhibition and, in some cases, enhanced efficacy when venom-based agents are combined with nanoparticle delivery systems or conventional anticancer drugs. However, a significant proportion of evidence is limited to in vitro studies, with substantial heterogeneity in venom sources, extraction methods, dosages, and cancer models, which constrains generalizability. There is also a lack of systematic data on long-term toxicity, immunogenicity, off-target effects, pharmacokinetics, and formulation challenges. Taken together, these findings highlight snake venom-derived compounds as promising multi-targeted anticancer agents but underscore the urgent need for standardized formulations, rigorous preclinical safety assessments, and translational research to bridge the gap to clinical application. Future investigations should aim to isolate novel venom-derived compounds, refine delivery strategies, and undertake rigorous preclinical safety and pharmacokinetic studies—ultimately moving toward early-phase clinical evaluation to bridge the translational gap and assess the therapeutic potential of these agents. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; and radiotherapy damages surrounding organs and compromises the patients’ immune function. Methods: Herein, we designed a carrier-free nanodrug delivery system composed of self-assembled Curcumin nanoparticles (NPs) coated with a tannic acid (TA)/Fe(III) network (denoted as CUR@TA-Fe(III) NPs). We systematically evaluated the in vitro cytotoxicity and photothermal–ferroptosis synergistic therapeutic efficacy of CUR@TA-Fe(III) NPs in 4T1 breast cancer cells, as well as the in vivo antitumor activity using 4T1 tumor-bearing mouse models. Results: CUR@TA-Fe(III) NPs had high drug loading efficiency (LE) of 27.99%, good dispersion stability, and photothermal properties. Curcumin could inhibit the growth of 4T1 cancer cells, while TA-Fe(III) efficiently converted light energy into heat upon exposure to near-infrared (NIR) light, leading to direct thermal ablation of 4T1 cells. Additionally, TA-Fe(III) could supply Fe(II) via TA, increase intracellular Fe(II) content, and generate reactive oxygen species (ROS) through the Fenton reaction, in turn inducing lipid peroxidation (LPO), a decrease in mitochondrial membrane potential (MMP), and glutathione depletion, eventually triggering ferroptosis. Conclusions: This treatment strategy, which integrates CT, PTT, and ferroptosis, is expected to overcome the limitations of traditional single-treatment methods and provide a more effective method for the treatment of TNBC. Full article

Brazilian red propolis (BRP) has emerged as a promising source of multifunctional phytochemicals with potent anti-inflammatory activity. This review provides a comprehensive analysis of the anti-inflammatory effects of BRP’s bioactive compounds, their molecular targets, and their mechanisms of action. Isolated compounds from BRP (such as formononetin, biochanin A, daidzein, calycosin, medicarpin, vestitol, and neovestitol) have demonstrated the ability to modulate critical pro-inflammatory signaling pathways, including NF-κB, TLR4, JAK/STAT, and PI3K/AKT, while concurrently activating antioxidant and cytoprotective responses via the Nrf2/HO-1 axis. These effects are further supported by the suppression of pro-inflammatory cytokines, regulation of immune cell infiltration and activation, inhibition of inflammasome components such as NLRP3, induction of autophagy, and polarization of macrophages and microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype. Collectively, these findings reinforce the potential of BRP as a rich source of multifunctional phytochemicals with broad therapeutic relevance for chronic inflammation and related pathologies. Future research should address the identified knowledge gaps by employing rigorous in vitro and in vivo toxicity assessments, exploring structure–activity relationships, and leveraging advanced delivery systems to optimize bioavailability. Such methodological approaches will be essential for translating the promising biological activities of BRP compounds into clinically viable therapeutic agents. Full article

Increasing interest in functional nutrition has driven the incorporation of probiotics into pet food formulations to enhance digestive health, immune response, and overall well-being in companion animals. This systematic review examines scientific publications, patents, and market developments related to probiotic-enriched pet food from 2014 to 2024. We evaluate major probiotic taxa—including Lactobacillus spp., Bifidobacterium spp., Bacillus spp., and Saccharomyces cerevisiae—based on their resilience during processing, gastrointestinal survival, and documented health benefits. Delivery technologies such as microencapsulation, coating matrices, and post-processing supplementation are analyzed for their effectiveness in preserving probiotic viability within dry and wet food matrices. Patent landscape analysis highlights innovation trends in strain selection, formulation design, and processing methods. In vivo and in vitro studies demonstrate that probiotic supplementation modulates gut microbiota composition, improves fecal parameters, enhances immune markers, and promotes nutrient absorption in both canine and feline models. Market data reveal rapid expansion of commercial probiotic pet food products, yet scientific research remains limited compared to human nutrition. Overall, the findings indicate that while probiotics hold clear potential to improve gastrointestinal health and immunity in pets, evidence remains fragmented, particularly for cats and long-term outcomes. Bridging the gap between industrial innovation and controlled clinical validation will be essential for developing next-generation probiotic pet foods. Full article

Cardiac hypertrophy is a critical contributor to cardiac dysfunction and the development of heart failure, yet effective therapeutic strategies remain limited. Propylene glycol alginate sulfate sodium (PSS) is a marine sulfated polysaccharide drug used in the treatment of cardiovascular diseases and has shown cardiac function benefits. Here, we designed a pH-responsive PSS-loaded nanoparticle drug delivery system. It was self-assembled by negatively charged PSS with positively charged trimethyl chitosan glycocholic acid (TMC-GA) via electrostatic interaction, and further stabilized the nanoparticles with Hydroxypropyl methylcellulose phthalate (HP55) excipients. The prepared TMC-GA/HP55@PSS nanoparticles were spherical, with a mean particle size of 361.5 ± 1.26 nm, zeta potential of −30.3 ± 0.9 mV, and encapsulation efficiency of 92.52 ± 2.4%. In vitro release study demonstrated the pH-responsive property of TMC-GA/HP55@PSS under intestinal conditions and facilitated nanoparticles absorption in the intestinal epithelium. In vitro experiments confirmed the biocompatibility of PSS and its ability to improve myocardial cell hypertrophy. In vivo, both PSS and its nanoparticles significantly ameliorated pressure overload–induced cardiac hypertrophy in mice, with TMC-GA/HP55@PSS exhibiting better cardioprotective efficacy. This study is the first to integrate pH-responsiveness and bile acid transport-mediated uptake into PSS nanocarrier systems. The findings provide valuable data and enlightenment for designing novel formulations and expanding the clinical applications of PSS. Full article

Androgenetic alopecia (AGA), the most common form of hair loss, imposes considerable psychosocial and medical burdens. Current topical treatments are limited by suboptimal efficacy, slow onset, side effects, and poor patient adherence. Although numerous reviews have explored natural plant-based strategies for managing AGA, most offer fragmented evidence with limited systematic correlation between mechanistic studies and clinical outcomes concerning single plant constituents. This review critically synthesizes recent pharmaceutical advances in AGA therapy, with a focus on the synergistic potential of multifunctional plant extracts integrated with nanotechnology enhanced cutaneous delivery systems. We begin by examining the mechanistic basis of AGA pathogenesis and the limitations of existing treatments to identify unmet therapeutic needs. Next, we systematically evaluate plant extracts supported by robust in vitro, in vivo, and clinical evidence for their anti-androgenic, anti-inflammatory, antioxidative, and anti-apoptotic properties. Finally, we address key biopharmaceutical challenges in transdermal delivery for AGA and discuss how nanocarriers can overcome these barriers to improve local drug bioavailability and target specificity. By bridging phytochemistry and nanomedicine, this review provides novel insights and a pharmaceutics-oriented framework aimed at developing safer, more effective, and patient-compliant topical therapies for AGA. Full article

Background: Skin mycoses affect approximately 10% of the global population, and the range of effective topical antifungal agents remains limited. Voriconazole (VRC) is a broad-spectrum triazole with proven efficacy against drug-resistant fungal infections. This study aimed to develop and optimize VRC-loaded microemulsion (ME) polymer gels (Carbopol^®-based) for cutaneous delivery. Selected formulations also contained menthol (2%) as a penetration enhancer and potential synergistic antifungal agent. Methods: A comprehensive screening was performed using pseudoternary phase diagrams to identify stable oil/surfactant/co-surfactant/water systems. Selected MEs were prepared with triacetin, Etocas™ 35, and Transcutol^®, then gelled with Carbopol^®. Formulations were characterized for pH, droplet size, polydispersity index (PDI), and viscosity. In vitro VRC release was assessed using diffusion cells, while ex vivo permeation and skin deposition studies were conducted on full-thickness human skin. Rheological behavior (flow curves, yield stress) and texture (spreadability) were evaluated. Antifungal activity was tested against standard strain of Candida albicans and clinical isolates including a fluconazole-resistant strain. Results: The optimized ME (pH ≈ 5.2; droplet size ≈ 2.8 nm) was clear and stable with both VRC and menthol. Gelation produced non-Newtonian, shear-thinning hydrogels with low thixotropy, favorable for topical application. In ex vivo studies, performed with human skin, both VRC-loaded gels deposited the drug in the epidermis and dermis, with no detectable amounts in the receptor phase after 24 h, indicating retention within the skin. Menthol increased VRC deposition. Antifungal testing showed that VRC-containing gels produced large inhibition zones against C. albicans, including the resistant isolate. The VRC–menthol gel exhibited significantly greater inhibition zones than the VRC-only gel, confirming synergistic activity. Conclusions: ME-based hydrogels effectively delivered VRC into the skin. Menthol enhanced drug deposition and demonstrated synergistic antifungal activity with voriconazole. Full article

Research into oral mucosa-targeted drug delivery systems (DDS) is rapidly evolving, with growing emphasis on enhancing bioavailability and precision targeting while overcoming the unique anatomical and physiological barriers of the oral environment. Despite considerable progress, challenges such as enzymatic degradation, limited mucosal penetration, and solubility issues continue to hinder therapeutic success. Recent advancements have focused on innovative formulation strategies—including nanoparticulate and biomimetic systems—to improve delivery efficiency and systemic absorption. Simultaneously, smart and stimuli-responsive materials are emerging, offering dynamic, environment-sensitive drug release profiles. One particularly promising area involves the application of glycosaminoglycans, a class of naturally derived polysaccharides with excellent biocompatibility, mucoadhesive properties, and hydrogel-forming capacity. These materials not only enhance drug residence time at the mucosal site but also enable controlled release kinetics, thereby improving therapeutic outcomes. However, critical research gaps remain: standardized, clinically meaningful mucoadhesion/permeation assays and robust in vitro–in vivo correlations are still lacking; long-term stability, batch consistency of GAGs, and clear regulatory classification (drug, device, or combination) continue to impede scale-up and translation. Patient-centric performance—palatability, mouthfeel, discreet wearability—and head-to-head trials versus standard care also require systematic evaluation to guide adoption. Overall, converging advances in GAG-based films, hydrogels, and nanoengineered carriers position oral mucosal delivery as a realistic near-term option for precision local and selected systemic therapies—provided the field resolves standardization, stability, regulatory, and usability hurdles. Full article

Background: Although DNA vaccines offer a flexible platform for tumor immunotherapy, their weak immunogenicity remains a key limitation. This study aimed to improve the immunogenicity of DNA vaccines by enhancing the efficiency of tumor neoantigen delivery through extracellular vesicles (EVs), thereby promoting stronger dendritic cell (DC) activation and antitumor responses. Methods: A novel DNA vaccine (pCSP) was engineered by fusing tumor-specific neoantigens to the EV-associated protein CD63 and incorporating a SARS-CoV-2 receptor-binding domain (RBD) fragment to facilitate EV uptake by DCs. The resulting EVs were expected to carry neoantigens into the immunoproteasome for major histocompatibility complex I (MHC-I) presentation. The immunological and antitumor effects of pCSP were assessed through in vitro functional assays and in vivo experiments in a murine pancreatic cancer model. Safety was evaluated through histological and biochemical analyses. Results: In vitro, pCSP significantly promoted EV internalization by DCs by approximately twofold and enhanced their immune activation, as evidenced by elevated cytokine production. In vivo, pCSP markedly suppressed tumor growth with a decrease in volume by over 70% relative to controls, boosted CD8+ T cell responses, and increased immune infiltration into the tumor microenvironment. Safety assessments revealed that while liver/kidney function markers were within physiological ranges, mild inflammatory infiltrates were consistently observed in the lungs, indicating a localized safety concern that warrants further monitoring. Conclusions: The pCSP vaccine enhances the immunogenicity of neoantigen DNA vaccines by improving EV uptake and immune activation in DCs. These findings provide a potential strategy for improving DNA vaccine efficacy in the context of cancer immunotherapy while maintaining acceptable safety. Full article

Background/Objectives: Conventional therapeutic strategies exhibit limited efficacy against pancreatic cancer, primarily due to its profoundly hypoxic tumor microenvironment and dense fibrotic stroma. Chemodynamic therapy (CDT) holds promise; however, its application in pancreatic cancer is restricted by insufficient endogenous hydrogen peroxide (H₂O₂) levels and the activation of protective autophagy in response to oxidative stress. Methods: To overcome these obstacles, we developed a tumor microenvironment-responsive, pancreatic cancer-targeted CDT nanoamplifier—H-MnO₂/GOX&CQ-iRGD—comprising a hollow mesoporous MnO₂ shell co-loaded with glucose oxidase (GOX) and chloroquine (CQ), and surface-functionalized with the tumor-penetrating peptide iRGD. GOX catalyzes glucose oxidation to generate H₂O₂, enhancing Fenton-like reactions. CQ suppresses autophagy induced by oxidative stress, thereby alleviating therapy resistance. The iRGD peptide targets integrin α_vβ₃, which is overexpressed on pancreatic cancer cells and tumor vasculature, promoting deep tumor penetration and enhanced delivery efficiency. Results: We comprehensively characterized the nanoplatform’s physicochemical properties, tumor microenvironment triggered degradation, controlled drug release, glucose-driven H₂O₂ generation, and hydroxyl radical production in vitro. Cellular studies assessed nanoparticle uptake, intracellular H₂O₂ production, autophagy inhibition, and cytotoxicity. In vivo experiments further demonstrated effective tumor targeting and significant therapeutic outcomes in pancreatic cancer models. Conclusions: This nanoplatform addresses major barriers of CDT—namely, insufficient H₂O₂ levels, autophagy-mediated resistance, and limited intratumoral penetration—offering a promising strategy for pancreatic cancer treatment. Full article

Background/Objectives: Controlling the timing of farrowing to occur during working hours presents an opportunity to improve supervision and reduce piglet neonatal mortality. However, the use of non-therapeutic injectable drugs is often limited in commercial swine production. This study aimed to develop a cloprostenol vaginal mucosal delivery system for induction of farrowing. To achieve this, two vaginal tablets containing cloprostenol were formulated for simultaneous insertion: an immediate-release (IR) tablet and a delayed release (DR) tablet, the latter designed for a 6 h delay before release. Methods: In vitro release studies demonstrated that the IR tablet released 100% of the drug within 5 min, while the DR tablet, initiated release after four hours and achieved approximately 80% release at six hours, aligning with the targeted release profile. To evaluate the efficacy of the optimized formulations, an in vivo study was conducted using 121 mixed parity Landrace × Large White sows that were assigned to one of four treatments, control (n = 23) received no treatment; IM (n = 26) received 185 µg of cloprostenol via intramuscular injection; IR (n = 36) received a 100 µg IR tablet by vaginal deposition; and IR + DR (n = 36) received both IR and DR tablets by vaginal deposition, to simulate split-dose delivery. Results: Control sows experienced longer (P < 0.001) intervals to farrowing compared to those receiving cloprostenol treatments. Additionally, differences (P < 0.05) were observed in interval from treatment to farrowing time among the treatments, with the interval for IM sows being shorter than for IR (P < 0.001) and IR + DR (P = 0.001) sows. Conclusions: These findings confirm that the vaginal route offers an alternative, non-invasive, method for farrowing induction in sows, facilitating farrowing supervision during working hours and potentially reducing piglet mortality. Full article

Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen that infects many animals with mild symptoms. However, swine is the most receptive host and causes acute and lethal myocarditis and/or encephalitis, and induces sudden death in piglets. There are currently no approved antivirals against EMCV. In recent years, antiviral therapies based on small interfering RNA (siRNA) have been rapidly developed as effective alternative therapies. In this study, we designed siRNAs targeting highly conserved regions in the EMCV genome coinciding with VP2 and 3C genes. We show that these siRNAs were non-immunostimulatory and significantly inhibited EMCV replication in vitro. The siRNAs were then complexed in liposomes before testing in a lethal EMCV mouse model in vivo. Both prophylactic and therapeutic intravenous delivery of siRNAs ameliorated viral infection in multiple organs and improved animal survival. This is the first demonstration of the use of a liposomal delivery platform to deliver highly conserved anti-EMCV siRNAs for EMCV antiviral therapy in vivo. Full article