Search Results (667)

Objectives: Rhizoma Coptidis alkaloids (RCAs) have been proven highly promising in diabetes therapy. However, poor solubility, low bioavailability, and a lack of an effective delivery strategy are major hurdles to improving clinical outcomes. Herein, mPEG-PLGA nanoparticles were employed to deliver RCA orally to enhance anti-diabetic effects. Methods: The RCA-loaded nanoparticles (RCA NPs) were prepared using the emulsion solvent diffusion method. The physicochemical properties of RCA NPs were characterized by morphology, particle size, zeta potential, polydispersity index, drug loading, and drug release. Pharmacokinetic and tissue distribution were determined by UPLC-MS/MS. The hypoglycemic effect was evaluated in a type 2 diabetes mouse model. To illustrate potential mechanisms of action, the expression of PI3K/Akt signaling pathway-related genes and their proteins was detected by RT-PCR and Western blot, respectively. Results: The prepared RCA NPs were spherical in structure, with a particle size of approximately 145 nm and a sustained drug release profile (approximately 50% within 24 h). Compared with RCAs, RCA NP bioavailability increased approximately 2.2-fold, and the hypoglycemic, hypolipidemic, hepatoprotective, anti-inflammatory effects were significantly improved. The better outcome might be due to upregulation of expression and phosphorylation levels within the IRS1/PI3K/AKT/GLUT4 signal pathway in liver tissues. Conclusions: RCA NPs hold great potential for further clinical translation. Full article

Objective: The therapeutic efficacy of the classic antibiotic combination trimethoprim/sulfamethoxazole (TMP/SMZ) is often limited by the significant pharmacokinetic mismatch. In this study, a polyethylene glycol-polylactic-co-glycolic acid (PEG-PLGA) nanodelivery system was employed to improve the pharmacokinetic matching of TMP and SMZ. The investigation also evaluated the enhanced in vivo antibacterial efficacy of this formulation. Methods: Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) was employed to systematically characterize the absorption, distribution, and excretion profiles of PEG-PLGA-loaded TMP nanoparticles (NPs) in rats. In vitro antibacterial activity was assessed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vivo efficacy and biosafety of the TMP NPs/SMZ regimen were evaluated using a murine E. coli infection model via survival monitoring, biochemical assays, and histopathology. Results: Pharmacokinetic analysis revealed that TMP NPs achieved a relative bioavailability of 193.05% and extended the elimination half-life by 3.37-fold compared to free TMP. Tissue distribution showed significantly increased drug accumulation in the liver, spleen, and kidneys, with renal clearance as the primary excretion pathway (73.89%). In vitro, the nano-formulation reduced the minimum inhibitory concentration (MIC) by 2-4-fold and shortened the bactericidal duration from 12 to 8 h. In vivo, the TMP NPs/SMZ combination significantly improved survival rates, accelerated recovery, and alleviated infection-induced organ damage without systemic toxicity. Conclusions: This nanotechnology-based strategy effectively aligns the pharmacokinetics of TMP and SMZ, prolongs their synergistic window, and enhances biosafety, offering a viable approach to revitalize classic antibiotic combinations. Full article

Background/Objectives: Acalypha monostachya is used in rural communities in Mexico as a traditional remedy for cancer, and we previously observed cytotoxic activity of its extracts against MDA-MB-231 and HeLa cells. Methods: Because lipophilic plant fractions disperse poorly in water, we encapsulated the hexane leaf extract (LHE) of A. monostachya in poly (lactic-co-glycolic acid) (PLGA) nanoparticles prepared by nanoprecipitation, characterized them physicochemically, and evaluated their in vitro cytotoxicity. Results: The selected extract/polymer ratio (5/50, w/w) produced nanoparticles with a mean diameter of 131.4 ± 0.5 nm and a PDI of 0.122 ± 0.028, with an encapsulation efficiency of 92.03% and a loading of 8.43%. We next evaluated cytotoxicity by MTT after 24 h in HeLa and MDA-MB-231 cells and compared the response with non-tumorigenic HaCaT keratinocytes. Encapsulation increased potency relative to free LHE, yielding IC₅₀ values of 30 µg/mL (HeLa), 60 µg/mL (MDA-MB-231), and 95 µg/mL (HaCaT). These values corresponded to selectivity indices of 3.2 (HaCaT/HeLa) and 1.6 (HaCaT/MDA-MB-231). Conclusions: Overall, encapsulation of LHE in PLGA nanoparticles yields an aqueous PLGA nanoparticle suspension and is associated with improved in vitro potency while maintaining measurable selectivity against cancer cells. Full article

Background/Objective: Effective topical delivery of 4-phenylbutyric acid (4-PBA) for arsenical vesicant-induced skin injury requires nanocarrier systems that maintain physicochemical and chemical stability during extended storage. This study systematically evaluated the six-month stability of five 4-PBA-loaded micro/nanoparticulate formulations—chitosan nanoparticles (N31, N35), emulsomes (E2), microsponges (MSs), and PLGA nanoparticles (P1)—to identify lead candidates suitable for field deployment and foam integration. Methods: Formulations were subjected to ICH-accelerated stability testing at 25 °C/60% RH and 40 °C/75% RH, with monthly evaluation of particle size, polydispersity index, zeta potential, drug content by HPLC, and chemical/thermal stability by FTIR and DSC. Results: N31 demonstrated superior colloidal stability, maintaining particle size within acceptable limits at both conditions despite progressive surface charge neutralization. E2 showed consistent drug content retention and preserved chemical integrity, though moderate vesicle fusion occurred. MS underwent complete physical degradation at 40 °C within the first month, while P1 exhibited hydrolytic degradation with substantial drug loss. N35 showed severe aggregation indicating colloidal instability. Conclusions: N31 and E2 emerged as lead candidates: N31 is recommended for field deployment where environmental control is limited, while E2 is suitable for controlled storage settings prioritizing drug loading capacity. Full article

Background: Nanoparticles are a promise for wound-healing therapies. However, its lack of efficacy/safety represents a real challenge for therapeutic use. Objectives: To overcome these problems, the ethanolic extract of Casimiroa edulis leaves, previously reported for its anti-inflammatory, antibiotic, and antioxidant activities, was characterized by FIA-ESI-FTICR-MS and encapsulated in biodegradable nanoparticles for potential wound-healing therapies. Methods:Casimiroa edulis-loaded nanoparticles (CE-NP) were prepared using the rapid emulsion-diffusion method and characterized by their particle size distribution, molecular interactions, charge, morphology, pH, physical stability, and antioxidant and occlusive effects. Results: A total of 40/34 ions in positive/negative electrospray ionization modes were obtained from the extract exploration analysis and were putatively annotated by accurate mass against databases with an error tolerance ≤10 mDa. The most abundant compounds showed the following order: tetramethylscutellarein > rutin > S-usnate > lactose > eugenol derivative > rotenone. While polyphenols predominated, carbohydrates, depsidones/other phenolics, etc., were also detected. The solid/spherical nanoparticles observed by TEM were obtained with a blend of acetone:methyl ethyl ketone (75:25) as the organic phase, producing a unimodal particle size (169.30 ± 1.30 nm; PdI = 0.08 ± 0.03). The encapsulation/loading percentages were 57 ± 0.74/1.62 ± 0.02%, ensuring an entrapment of half the extract, as observed in the FTIR studies. The light backscatter profiles show minimal differences, indicating physical stability correlated with the Z potential (−9.45 ± 1.73 mV). The antioxidant activity of the extract/nanoparticles at 40 µg/mL was 17.27 ± 2.86/16.73 ± 1.28 μg/mL, two-fold higher than that previously reported for sapote seeds. Conclusions: Biodegradable CE-NP with suitable characteristics were obtained for the first time, representing a preliminary proposal for wound healing. Efficacy studies are required. Full article

Luteolin (Ltn), a natural flavonoid, effectively inhibits microglial activation in Alzheimer’s disease (AD) with promising therapeutic potential, but its efficacy is severely limited by the blood–brain barrier (BBB). To overcome this obstacle, this study prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)—designated as TGN/RAP12-RBC-NPs@Ltn—which were coated with red blood cell membranes (RBCm) functionalized with two peptides, TGN (TGNYKALHPHN) and RAP12 (EAKIEKHNHYQK). The results demonstrated that TGN significantly enhanced BBB permeability, while RAP12 enabled effective targeting and delivery of TGN/RAP12-RBC-NPs@Ltn to microglial mitochondria in the brain. In addition, the presence of RBCm significantly inhibited the phagocytosis of NPs by macrophages, exerting a notable role in immune evasion. Meanwhile, the study confirmed that encapsulating Ltn within NPs significantly enhanced cognitive function in APP/PS1 mice, modulated the expression of key mitochondrial metabolic enzymes—pyruvate dehydrogenase (PDH) and its phosphorylated forms (pS232PDH, pS293PDH, pS300PDH)—in microglia, thereby ameliorating mitochondrial dysfunction and effectively regulating the neuroinflammatory environment in the mouse brain, and ultimately contributed to therapeutic efficacy. From this, it could be seen that TGN/RAP12-RBC-NPs@Ltn could significantly enhance the therapeutic effect of Ltn on AD, providing an effective treatment strategy for delaying the progression of AD. Full article

Vascular inflammation and endothelial dysfunction are key drivers in the development of cardiovascular and neurovascular diseases. Mitochondrial dysfunction and oxidative stress further amplify inflammatory cascades, emphasising the need for targeted strategies that restore endothelial homeostasis at the subcellular level. Hydrogen sulphide (H₂S) donors, such as AP39, offer cytoprotective benefits but are limited by short half-life and rapid release of the active compound, H₂S. We developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating AP39 (PLGA-AP39) to achieve sustained, mitochondria-targeted H₂S delivery. Nanoparticles were characterised by size, polydispersity, zeta potential, encapsulation efficiency, and in vitro release kinetics. Human umbilical vein endothelial cells (HUVEC) were exposed to TNF-α to induce inflammation, followed by treatment with free AP39 or PLGA-AP39. Anti-inflammatory effects were assessed by measuring IL-6, IL-8, and TGF-β levels. Mitochondrial function was evaluated using a Seahorse XFe24 Analyser, membrane potential assays, and mitochondrial ROS detection. Moreover, we investigated vascular function by analysing capillary-like tube formation and wound closure in response to treatments. PLGA-AP39 nanoparticles displayed a uniform size (~227 nm), low PDI, and high encapsulation efficiency (>78%). Sustained AP39 release was observed over seven days. Treatment with PLGA-AP39 significantly restored TNF-α-induced endothelial dysfunction and reduced TNF-α-induced release of IL-6, IL-8, and TGF-β compared to untreated controls. Seahorse analysis revealed restoration of maximal respiration and increased spare respiratory capacity. Encapsulated AP39 also preserved mitochondrial membrane potential and reduced mitochondrial ROS production, demonstrating enhanced protection against inflammation-induced metabolic dysfunction. This work establishes a novel nanoparticle-based strategy for prolonged, mitochondria-specific H₂S delivery to counteract vascular inflammation and enhance endothelial bioenergetics. The results from this work are pioneering in the generation of a novel delivery method for H₂S donors employing PLGA and represent a promising therapeutic avenue for treating chronic vascular inflammatory disorders. Full article

This study aims to assess the rate and duration of rat brain retention after a single intranasal administration of indocyanine green (ICG) as an aqueous solution or encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. Near-infrared fluorescence emission of ICG from the brain and visceral organs was measured at 1, 4, and 24 h, as well as at 1 and 2 weeks after administration. It was observed that both ICG formulations stained the olfactory bulbs and brainstem, the latter mainly in the basolateral region of the pons. Reduced staining was observed on day 7 after treatment, and the signal remains detectable on day 14. Additionally, while emission from ICG-labeled brains in water decreased after two weeks compared to day 7, in ICG-loaded nanoparticles, the emission was significantly higher on day 14. It is concluded that ICG is transported into the brain via both nose-to-brain delivery pathways—through and along olfactory or trigeminal nerves—and that ICG is a useful dye for in vivo studies due to its long-lasting emission and low toxicity. Furthermore, the suggested penetration of ICG-encapsulated PLGA nanoparticles via these transport mechanisms makes them a useful carrier for brain delivery of substances that are rapidly eliminated from circulation or do not cross the blood–brain barrier. Full article

Objectives: In response to the challenge that Staphylococcus aureus (S. aureus) vaccines fail to induce durable protective immunity, this study aims to develop a novel antigen-adjuvant co-design strategy. Specifically, we rationally combined the immunodominant toxin antigen LukS-PV with the immunologically subdominant adhesin antigen ClfA, co-delivered via the PLGA-PEG nanoadjuvant system, to elicit synergistic, durable, and balanced humoral and cellular immune responses. Methods: Firstly, recombinant antigens LukS-PV and ClfA were individually covalently conjugated to PLGA-PEG 25% nanoparticles (25% NPs) using EDC/NHS chemical coupling to construct a combined nanovaccine, followed by systemic safety verification in a mouse model. Subsequently, specific antibody titers were detected by ELISA, and the secretion levels of IL-4, IFN-γ, and IL-17A were measured by ELISPOT assay to comprehensively evaluate the humoral and cellular immune responses induced by the vaccine. Finally, the protective efficacy of the vaccine was assessed through acute and long-term (up to 180 days) lethal challenge experiments, thereby verifying the effectiveness of this co-design strategy based on rational antigen selection. Results: The combined vaccine group (25% NPs-rClfA + 25% NPs-rLukS-PV) not only elicited high levels of specific antibodies but, more importantly, induced robust cellular immune responses dominated by Th1 and Th17 cells. Challenge experiments confirmed that the protective efficacy of the combined vaccine was significantly superior to that of any single-antigen vaccine and provided complete protection for up to 180 days. Crucially, the same antigen combination formulated with a traditional aluminum adjuvant failed to confer this durable protection, underscoring the essential role of adjuvant synergy. Conclusions: This study demonstrates that rational combination of immunodominant and subdominant antigens with a compatible nanoadjuvant induces synergistic and durable immunity against S. aureus. This co-design strategy addresses key limitations of previous vaccines and provides a promising foundation for future clinical development. Full article

Background: Poly(lactic-co-glycolic) acid (PLGA) nanoparticles were found to be actively exocytosed from cells in a previous study in our lab. The exocytosis process can be modulated to increase the retention of nanoparticles within the cells so that the therapeutic efficacy of any drug encapsulated within the nanoparticles is increased. So, we wanted to know which membrane proteins were involved in the exocytosis process of the nanoparticles. The roles of VAMP3 and VAMP7, two crucial membrane proteins associated mainly with constitutive and regulated secretion, respectively, in cells, were studied in the context of exocytosis of PLGA nanoparticles. Materials and Methods: The siRNA-mediated knockdown of VAMP3 and VAMP7 genes was performed in the LN229 cancer cell line, and the intracellular accumulation of PLGA nanoparticles was studied by fluorescence microscopy. Results: There was no significant difference in the intracellular accumulation of the PLGA nanoparticles after siRNA-mediated knockdown of VAMP3 or VAMP7. Conclusion: This study shows that VAMP3 and VAMP7, which serve as important membrane proteins associated with the conventional constitutive and regulated secretion of different molecules in cells, are most likely not involved in the exocytosis/secretion of PLGA nanoparticles. So, the pathway of intracellular trafficking of PLGA nanoparticles needs to be deciphered, as it appears to be a non-conventional one. Full article

The present study reports the design and physicochemical characterization of a hybrid nanoparticle system for the potential intranasal delivery of galantamine (GAL), aimed at improving its bioavailability. Carbon dots (CDs) were used to load GAL, enhancing its dissolution and stability, and were subsequently incorporated into a poly(lactic-co-glycolic acid)–curcumin (PLGA–Cur) conjugate matrix. The successful formation of the PLGA-Cur conjugate was verified via ¹H-NMR and FTIR spectroscopy, while the loading of GAL and its physical state in the CDs was assessed via FTIR and pXRD, respectively. The resulting GAL-CD/PLGA–Cur nanoparticles were spherical, with particle sizes varying from 153.7 nm to 256.3 nm, a uniform morphology and a narrow size distribution. In vitro release studies demonstrated a multi-phase sustained release pattern extending up to 12 days. Spectroscopic and thermal analyses confirmed successful conjugation and molecular interactions between GAL and the carrier matrix. This proof-of-concept hybrid system demonstrates promising controlled, multi-phase sustained galantamine release in vitro, highlighting the role of curcumin conjugation in modulating polymer structure and release kinetics and providing a foundation for future biological evaluation. Full article

Background/Objective: Osimertinib (OSI) is a third-generation tyrosine kinase inhibitor approved for non-small cell lung cancer (NSCLC) therapy. OSI is administered orally; this route limits the amount of OSI reaching the tumor in the lungs and is associated with serious systemic toxicity. This study aimed to develop a dry powder inhalable formulation to provide tumor-targeted delivery and minimize systemic toxicity. To the best of our knowledge, this is the first study to prepare and evaluate a dry powder inhalation formulation of OSI. Methods: Chitosan-coated PLGA nanoparticles (PLGA-C NPs) encapsulating OSI were prepared using a single emulsion-solvent evaporation technique. PLGA-C NPs were assembled into respirable nanocomposite microparticles (NCMPs) via spray drying with L-leucine as a carrier. PLGA-C NPs were characterized for particle size, zeta-potential, encapsulation efficiency, and in vitro efficacy in A-549 cell line. NCMPs were evaluated for solid-state properties, aerosolization performance, stability and in vitro release. Results: PLGA-C NPs exhibited a particle size of 145.18 ± 3.0 nm, high encapsulation efficiency and a positive zeta potential. In vitro studies demonstrated a 3.6-fold reduction in IC50 compared to free OSI, superior antimigratory effects and enhanced cell cycle arrest. Solid-state characterization of NCMPs demonstrated drug encapsulation in the polymer without chemical interaction. NCMPs exhibited excellent aerosolization (mass median aerodynamic diameter of 1.09 ± 0.23 μm, fine particle fraction of 73.48 ± 8.6%) and sustained drug release (61.76 ± 3.9% at 24 h). Stability studies confirmed the physicochemical stability integrity. Conclusions: These findings suggest that this novel dry powder inhalable OSI formulation may improve therapeutic outcomes while reducing systemic toxicity. Full article

There is a growing demand for plant-derived antioxidants to replace synthetic ones in skincare applications. Phytochemicals are characterized by certain limitations, including poor bioavailability and chemical instability, which affect their industrial exploitation. Tomato peel extract has been used as a source of lycopene, which is renowned for its antioxidant properties. To improve the bioavailability of extracted lycopene, polymeric (poly-lactic-co-glycolic acid) nano-carriers were synthesized by comparing two non-ionic surfactants, polyvinyl alcohol (PVA) and Tween 20. The impact of surfactants has been studied by evaluating: (i) colloidal stability determined by dynamic light scattering; (ii) lycopene retention and bioactivity over time, as measured by spectrophotometric assays; (iii) biological interactions on 2D and 3D keratinocyte and melanocyte cell cultures. It was found that both surfactants enable the formation of stable lycopene-loaded nanoparticles suspensions; however, greater colloidal stability was exhibited by nanoparticles prepared with Tween 20. PVA, on the other hand, provided greater nanoparticle stability in terms of loaded lycopene retention and antioxidant activity. Tween 20 surfactant improves the internalization of lycopene-loaded nanoparticles in human skin spheroids. It was demonstrated that both surfactants provided excellent intracellular antioxidant activity of lycopene. This was observed in keratinocytes, melanocytes, adherent cells, and spheroids, suggesting potential skincare applications. Full article

Background: While intravenous administration of nanoparticles (NPs) is effective for targeting the lungs and liver, directing them to other organs and tissues remains challenging. Methods: Here, we report alternative administration routes that improve organ-specific accumulation of poly (lactic-co-glycolic acid) (PLGA) NPs (100 nm, negatively charged) loaded with the near-infrared dye Cyanine 7 (Cy7). NP cytotoxicity was evaluated in HEK293, mMSCs, C2C12, L929, and RAW264.7 cells. Hemocompatibility was assessed using WBCs and RBCs. NPs were administered via the tail vein, carotid, renal, and femoral arteries in BALB/c mice. Administration safety was evaluated by laser speckle contrast imaging and histological analysis. NP biodistribution and accumulation were assessed using in vivo and ex vivo fluorescence tomography and confocal microscopy of cryosections. Results: PLGA-Cy7 NPs demonstrate low cytotoxicity even at high doses and exhibit good hemocompatibility. Administration of NPs through the mouse carotid, renal, and femoral arteries significantly increases accumulation in the target ipsilateral brain hemisphere (31.7-fold) and salivary glands (28.3-fold), kidney (13.7-fold), and hind paw (3.6-fold), respectively, compared to intravenous administration. Injection of NPs through arteries supplying the target organs and tissues does not result in significant changes in blood flow, morphological alterations, or irreversible embolization of vessels, provided the procedure is performed correctly and the optimal dosage is used. Conclusions: These results highlight the potential of intra-arterial delivery of NPs for organ-specific drug targeting, underscoring the synergistic impact of advances in materials science, minimally invasive endovascular surgery, and nanomedicine. Full article

Background/Objectives: Cancer is a major health concern involving abnormal cell growth. Combining anticancer agents can enhance efficacy and overcome resistance by targeting multiple pathways and creating synergistic effects. Methods: This study used in silico approaches to evaluate the physicochemical and pharmacokinetic profiles of the innovative organoselenium nucleoside analog Di3a, followed by the design of two nanocarriers. Di3a-loaded PLGA nanocapsules and nanostructured lipid carriers based on compritol were prepared and evaluated alone and combined with doxorubicin (DOX) and docetaxel (DTX) for a synergistic effect. Results: Di3a subtly violated some of Lipinski’s rules, but still showed suitable pharmacokinetic properties. Both nanoparticles presented nanometric size, negative zeta potential and polydispersity index values < 0.20. Hemolysis assay suggested a pH-dependent pattern conferred by the surfactant 77KL, and evidenced the biocompatibility of the formulations, aligning with the results observed in the nontumor L929 cell line. The lack of drug release studies under varying pH conditions constitutes a limitation and warrants further investigation to validate the pH-responsive properties of the nanocarriers. MTT assay revealed that both formulations exhibited significant cytotoxic effects in the A549 cell line. However, neither formulation exhibited marked toxicity toward NCI/ADR-RES, a resistant tumor cell line. Conversely, when combined with DOX or DTX, the treatments were able to sensitize these resistant cells, achieving expressive synergistic antitumor activity. Conclusions: Despite the limitations in the in silico studies, the study highlights the potential of combining the proposed nanocarriers with conventional antitumor drugs to sensitize multidrug-resistant cancer cells and emphasizes the safety of the developed nanoformulations. Full article