Controlled Release Properties Research Articles

Carboxymethyl Chitosan-Coated Cyanidin-3-O-Glucoside-Beared Nanonutriosomes Suppress Palmitic Acid-Induced Hepatocytes Injury.

Cyanidin-3-O-glucoside (C3G) is classified as an anthocyanin (ACN) and is recognized for its remarkable antioxidant properties. Yet, the inadequate physicochemical stability of C3G restricts its potential for various biological applications. Thus, in this study, carboxymethyl chitosan (CMC)-coated nanonutriosomes (NS) were synthesized as a novel carrier for encapsulating C3G (CMC-C3G-NS) to improve C3G stability. CMC-C3G-NS exhibited a diameter of less than 200 nm along with an encouraging encapsulation efficiency exceeding 90%. Notably, the formulated CMC-C3G-NS possessed better stability under various pH, ionic, and oxygen conditions, improved controlled release properties, and higher hepatocellular uptake than uncoated particles (C3G-NS), indicating a longer retention time of C3G in a physiological environment. Of utmost significance, CMC-C3G-NS demonstrated superior alleviating effects against palmitic acid (PA)-induced oxidative hepatic damage compared to C3G-NS. Our study provided promising nanocarriers with the potential to deliver hydrophilic ACNs and controlled release properties for PA-induced hepatotoxicity alleviation.

Starch Glutaraldehyde Cross-Linked Hydrogel for Drug Release Properties

ABSTRACT In this study, we synthesized and characterized a novel starch glutaraldehyde cross-linked hydrogel for drug release. The hydrogel exhibited excellent properties such as absorption capacity and drug release. By optimizing the cross-linking reaction using varying concentrations of glutaraldehyde and reaction time, we obtained a hydrogel with a three-dimensional network structure, superior swelling properties, and mechanical strength. The results revealed doxycycline sustained and controlled drug release over a prolonged period, which could be adjusted by altering the cross-linking density of the hydrogel. Overall, the starch glutaraldehyde cross-linked hydrogel shows great promise as a drug delivery system with controlled release properties, applicable in pharmaceuticals and tissue engineering.

Biodegradable SPI-based hydrogel for controlled release of nanomedicines: a potential approach against brain tumors recurrence

Glioblastoma (GB) is the most common and aggressive brain tumor. The treatment for newly diagnosed glioblastoma is surgical resection of the primary tumor mass, followed by radiotherapy and chemotherapy. However, recurrences frequently occur in proximity to the surgical resection area. In these cases, none of the current therapies is effective. Recently, implantable biomaterials seem to be a promising strategy against GB recurrence. Here, for the first time we combined the tailorable properties of soy-protein hydrogels with the versatility of drug-loaded liposomes to realize a hybrid biomaterial for controlled and sustained nanoparticles release. Hydrogel consisting of 18-20% w/v soy-protein isolated were fabricated in absence of chemical cross-linkers. They were biodegradable (-10% and -30% of weight by hydrolytic and enzymatic degradation, respectively in 3 days), biocompatible (>95% of cell viability after treatment), and capable of sustained release of intact doxorubicin-loaded liposomes (diffusion coefficient between 10-18 and 10 -19 m2 s-1). A proof-of-concept in a “donut-like” 3D-bioprinted model shows that liposomes released by hydrogels were able to diffuse in a model with a complex extracellular matrix-like network and a 3D structural organization, targeting glioblastoma cells.The combination of nanoparticles' encapsulation capabilities with the hydrogels' structural support and controlled release properties will provide a powerful tool with high clinical relevance that could be applicable for the treatment of other cancers, realizing patient-specific interventions.

Black rice anthocyanins nanoparticles based on bovine serum albumin and hyaluronic acid: Preparation, characterization, absorption and intestinal barrier function protection in Caco-2 monolayers

Black rice anthocyanins (BRA) nanoparticles (NPs) were prepared using hyaluronic acid (HA), oxidized hyaluronic acid (OHA) and bovine serum albumin (BSA) to enhance the absorption and bioactivity of anthocyanins (ACNs). Results showed that HA/OHA-BSA-BRA NPs had a spherical morphology and excellent dispensability, with hydrated radius ~ 500 nm, zeta potential ~ − 30 mV, and encapsulation efficiency ~21 %. Moreover, using in vitro gastrointestinal release assay, we demonstrated that both BRA-loaded NPs exhibited effective controlled release properties of ACNs, significantly enhancing the accessibility of ACNs to the intestine. Cellular experiments showed that both two NPs had good biocompatibility and increased uptake of BRA. Furthermore, in comparison to the free BRA group, both BRA NPs groups significantly decreased the TEER value and increased the expression of tight junction proteins (Claudin 1, Occludin and ZO-1) in Caco-2 cell monolayers with LPS-induced damage. Therefore, our study demonstrated that HA/OHA-BSA-BRA NPs are promising carriers of ACNs and can effectively prevent the LPS-induced intestinal barrier injury in vitro.

Lychee peel extract-based magnetic iron oxide nanoparticles: Sustainable synthesis, multifaceted antioxidant system, and prowess in eco-friendly food preservation

The quest for sustainable synthesis methods has led to the exploration of lychee peel extract (LCPEx) as an eco-friendly alternative in the field of nanomaterials. This groundbreaking study introduces the synthesis of lychee peel extract-based magnetic iron oxide nanoparticles (LCPEx-MIONPs) and delves into their diverse applications. The meticulous methodology involved a multistep process for lychee peel extraction, resulting in the creation of LCPEx. The subsequent synthesis of LCPEx-MIONPs, achieved by combining the extract with iron chloride as a precursor and sodium hydroxide as a pH adjustor (set to 7.5), yielded nanoparticles with nanoscale dimensions (8.7± 0.4 nm) and diverse morphologies (cubic, hexagonal, spherical). Comprehensive characterization techniques, including Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), unveiled the structural attributes of LCPEx-MIONPs. The LCPEx exhibited robust antioxidant activity against DPPH, reaching its maximum inhibitory within only 5 minutes in a simple disc diffusion. The multifaceted antioxidant system of LCPEx-MIONPs exhibited an IC50 value of 202.3 µg/mL, highlighting the synergistic effects of lychee phytochemicals and magnetic ions. Beyond antioxidant capabilities, LCPEx-MIONPs, when incorporated into banana-based food preservation films, demonstrated significant prowess in grape preservation. The controlled release properties led to a notable reduction in water loss (9.3% on day 3 and 19.7% on day 6) compared to control grapes without LCPEx-MIONPs incorporated (18.2% on day 3 and 34.8% on day 6). This study significantly contributes to green nanotechnology, food preservation, and the development of eco-friendly hydrogels and bioplastic films, emphasizing the versatile applications of LCPEx-MIONPs in antioxidants, sustainable food preservation, and hydrogel-based bioplastics.

Redox-sensitive self-assembling polymer micelles based on oleanolic modified hydroxyethyl starch: Synthesis, characterisation, and oleanolic release

Our study aimed at developing polymer micelles that possess redox sensitivity and excellent controlled release properties. 3,3′-dithiodipropionic acid (DTDPA, Abbreviation in synthetic polymers: SS) was introduced as ROS (Reactive oxygen species)response bond and connecting arm to couple hydroxyethyl starch (HES) with oleanolic acid (OA), resulting in the synthesis of four distinct grafting ratios of HES-SS-OA. FTIR (Fourier Transform infrared spectroscopy) and 1H NMR (1H Nuclear magnetic resonance spectra) were used to verify the triumphant combination of HES-SS-OA. Polymer micelles were found to encapsulate OA in an amorphous form, as indicated by the results of XRD (X-ray diffraction) and DSC (Differential scanning calorimetry). When the OA grafting rate on HES increased from 7.72 % to 11.75 %, the particle size decreased from 297.79 nm to 201.39 nm as the polymer micelles became compact due to enhanced hydrophobicity. In addition, the zeta potential changed from −16.42 mv to −25.78 mv, the PDI (polydispersity index) decreased from 0.3649 to 0.2435, and the critical micelle concentration (CMC) decreased from 0.0955 mg/mL to 0.0123 mg/mL. Results of erythrocyte hemolysis, cytotoxicity and cellular uptake illustrated that HES-SS-OA had excellent biocompatibility and minimal cytotoxicity for AML-12 cells. Disulfide bond breakage of HES-SS-OA in the presence of H2O2 and GSH confirmed the redox sensitivity of the HES-SS-OA micelles and their excellent controlled release properties for OA. These findings suggest that HES-SS-OA can be potentially used in the future as a healthcare drug and medicine for the prevention or adjuvant treatment of inflammation.

Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Preparation of gelatin/ĸ-carrageenan active films through procyanidins crosslinking: Physicochemical, structural, antioxidant and controlled release properties

Active film is an emerging technology for food preservation, which can effectively control the sustained release of antioxidants. Herein, procyanidins were incorporated into gelatin films as a cross-linking agent and antioxidant to improve the physical and antioxidant properties of the gelatin films, and different amounts of ĸ-carrageenan were also added to increase the tortuosity of procyanidins diffusion paths (gelatin:ĸ-carrageenan (G:C) = 1:2, 1:1, and 2:1), resulting in a sustained release of procyanidins. The films were evaluated for their mechanical, barrier, morphological, antioxidant, and controlled release properties. The results showed that the incorporation of procyanidins improved the mechanical, moisture resistance and optical properties of the films. FTIR measurements and molecular docking confirmed the crosslinking reaction between procyanidin and gelatin/ĸ-carrageenan. XRD and SEM showed that these three compounds had good compatibility. Procyanidins could improve the antioxidant activity of films. Moreover, the content of ĸ-carrageenan was closely related to the release of procyanidins, and the film containing 1% (w/w) gelatin, 1% (w/w) ĸ-carrageenan, and 2% (w/w) procyanidins (G/C1:1/P) showed the lowest total release of procyanidins in 50% and 95% ethanol simulants. Gelatin/ĸ-carrageenan films with procyanidins could be used as a controlled-release film for food packaging applications.

Synergistic preparation and application in PCU of α-calcium sulfate hemihydrate whiskers from phosphogypsum and electrolytic manganese residue

The α-calcium sulfate hemihydrate whiskers (α-CSHWs) were first prepared using phosphogypsum (PG) and electrolytic manganese residue (EMR) as raw materials for coating urea, demonstrating excellent controlled-release properties. The effects of different reaction conditions on α-CSHWs, achieved by optimizing the reaction time, the concentrations of NH4+, Mn2+, and other factors, were discussed. Results showed that when the EMR content was 25 wt%, the reaction temperature was 100 °C, and the reaction time was 3 h, α-CSHWs with a length-to-diameter ratio of 39 were obtained. Through experiments and density functional theory (DFT), the mechanism of α-CSHWs preparation was elucidated. The results show that the addition of EMR reduces the content of impurity ions PO43− and F− in PG while introducing NH4+ and Mn2+. Interestingly, both NH4+ and Mn2+ can reduce the nucleation time of α-CSHWs, while PO43−, Mn2+, and F− are more likely to adsorb on the (0 0 6) crystal plane of α-CSHWs, NH4+ readily adsorbs on the (4 0 0) crystal plane. The controlled-release performance of modified α-CSHWs incorporated into polyurethane-coated urea (PCU) was investigated, and it was found that the addition of Mα significantly prolonged the nutrient release period, with the period extending up to 116 days for coatings of 5wt% and above. This work not only enhances the efficiency of PG and EMR utilization but also serves as a reference for the straightforward synthesis and application of α-CSHWs.

Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine.

Peptide and protein nanostructures with tunable structural features, multifunctionality, biocompatibility and biomolecular recognition capacity enable development of efficient targeted drug delivery tools for precision medicine applications. In this review article, we present various techniques employed for the synthesis and self-assembly of peptides and proteins into nanostructures. We discuss design strategies utilized to enhance their stability, drug-loading capacity, and controlled release properties, in addition to the mechanisms by which peptide nanostructures interact with target cells, including receptor-mediated endocytosis and cell-penetrating capabilities. We also explore the potential of peptide and protein nanostructures for precision medicine, focusing on applications in personalized therapies and disease-specific targeting for diagnostics and therapeutics in diseases such as cancer.

PH sensitive adriamycin-incorporated nanoparticles self-assembled from amphiphilic chitosan derivatives with enhanced antioxidant and antitumor activities

Development of secure and efficient drug delivery systems to overcome physicochemical challenges in cancer clinical treatment is one of the most active fields, and novel drug carriers are actively sought. In this work, the successful synthesis of amphiphilic chitosan derivatives containing pyridine cations and folic acid (TMACMCF) was confirmed by FTIR and 1H NMR spectroscopy. The critical micelle concentration (CMC) of TMACMCF was studied, and the results indicated that it possessed a relatively low CMC (0.186 mg/mL). Self-assembled nanoparticles (TMACMCF-ADM NPs) for the entrapment and delivery of adriamycin (ADM) were synthesized based on TMACMCF, and the morphology, particle size, zeta potential, sustained release performance, antioxidant and antitumor activities, and cytotoxicity were investigated. The particle size of TMACMCF-ADM NPs was 163.79 ± 7.31 nm, and the morphology observed by SEM and TEM showed spherical or oval particles. TMACMCF-ADM NPs showed excellent entrapment of ADM with entrapment efficiency and drug loading efficiency of 65.04 ± 1.20 % and 22.73 ± 0.40 %, respectively. The release performance results showed that in vitro release profiles of ADM from NPs exhibited pH-sensitive controlled and sustained release properties. The assay of antioxidant activity exhibited that TMACMCF-ADM NPs possessed significantly improved scavenging ability against three kinds of radicals (Superoxide-radical, DPPH radical, and ABTS radical). Moreover, the assay of antitumor activity by CCK-8 test exhibited that nanoparticles led to statistically significant enhancement in inhibition index for four kinds of cancer cells (BGC-823, MCF-7, HEPG-2, and A549). This work provides a promising carrier for secure and effective entrapment and delivery of ADM.

Zein and tannic acid hybrid particles improving physical stability, controlled release properties, and antimicrobial activity of cinnamon essential oil loaded Pickering emulsions

Pickering emulsion loading essential oil has demonstrated a promising strategy as delivery system in food preservation, but localization in stability and antimicrobial activity limits application. In this study, Pickering emulsions co-loaded with tannic acid and cinnamon essential oil (ZTC) have been developed based on zein and tannic acid complexes (ZT) mediated interfacial engineering. Fourier transform infrared, fluorescence spectroscopy, and molecular docking results indicated tannic acid altered the structural of zein. Interfacial tension results indicated that tannic acid accelerated the adsorbed speed of zein particles by decreased interfacial tension (11.99–9.96 mN/m). ZT5 formed a viscoelastic and dense layer in oil–water interface than that for other ZTs, which improved stability and control release performance of ZTC. Furthermore, the ZTC showed an effective antimicrobial activity against spoilage organisms Pseudomonad paralactis MN10 and Lactobacillus sakei VMR17. These findings provide new insight for developing co-loaded multiple antimicrobial agents within Pickering emulsion as a delivery system.

Development of the Antioxidant Property of Seagrass Extract-Based Hydrogel for Dental Application.

Background Seagrass is rich in antioxidants, which can help neutralize harmful free radicals in the oral cavity. Free radicals can contribute to oxidative stress, inflammation, and various oral health issues. Incorporating seagrass extract into a hydrogel can enhance its antioxidant capacity, providing a protective effect for oral tissues. The hydrogel, composed of a biocompatible base, ensures that the material is well-tolerated by oral tissue. This is crucial for any dental application to avoid adverse reactions. Aim This work aimed to develop an antioxidant hydrogel that incorporates seagrass extract, with a specific emphasis on its possible use in dentistry. Methods A seagrass sample was collected, and its bioactive compounds were extracted through the utilization of methanol, and subsequent filtration was done. The resulting seagrass filtrate was then integrated into a hydrogel, which was synthesized using polyacrylamide and sodium alginate. Antioxidant hydrogel underwent testing for antioxidant activity through both the 2,2-diphenyl-1-picrylhydrazyl assay and the 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) assay. Besides, the hydrogel functional groups were investigated using Fourier transform infrared spectroscopy, while its crystalline structure was examined using X-ray diffraction analysis. Conclusion Seagrass extract provides inherent antioxidant properties, and incorporating this bioactive extract into the hydrogel imparts antioxidant features. The hydrogel's controlled-release property ensures both safety and efficiency. Antioxidant hydrogel for dental applications holds the potential to improve oral health.

Preparation, stability and controlled release properties of starch-based micelles for oral delivery of hydrophobic bioactive molecules

Amphiphilic starches incorporating fatty acid ester chains of varying lengths and degrees of substitution (DS) were synthesized to fabricate starch-based micelles for oral delivery of hydrophobic bioactive molecules. The assembly of the amphiphilic starches is influenced by the concentration, temperature, and the chain length and DS of their fatty acid ester chain. Highly acidic environment can hydrolyze the amphiphilic starches, resulting in the formation of small-sized micelles. Conversely, high ionic concentration hinders the self-assembly of amphiphilic starches and the digestive fluids can dilute the amphiphilic starches concentration, leading to the micelle dissociation. However, amphiphilic starches with longer chain length and/or higher DS of the fatty acid ester chain possess greater hydrophobicity, enhancing the stability of starch-based micelles under varying conditions and favouring the protection of Trp-2 peptides during storage. The micelles demonstrate high cell bioaccessibility for Trp-2 peptides, with 59.25 % of Trp-2 peptides being transferred by the intestinal epithelium. These findings suggest a potential starch-based micelle system can be adjusted for the oral delivery of hydrophobic bioactive molecules.

Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy.

Development and characterization of potential larvicidal nanoemulsions against Aedes aegypti.

Plant-based insecticides offer advantages such as negligible residual effects, reduced risks to both humans and the environment, and immunity to resistance issues that plague conventional chemicals. However, the practical use of monoterpenes in insect control has been hampered by challenges including their poor solubility and stability in aqueous environments. In recent years, the application of nanotechnology-based formulations, specifically nanoemulsions, has emerged as a prospective strategy to surmount these obstacles. In this study, we developed and characterized nanoemulsions based on cymene and myrcene and assessed their toxicity both in vitro using human keratinocytes (HaCAT) cells and in an in vivo model involving Galleria mellonella larvae. Additionally, we investigated the insecticidal efficacy of monoterpenes against the mosquito Aedes aegypti, the primary dengue vector, via larval bioassay. Employing a low-energy approach, we successfully generated nanoemulsions. The cymene-based nanoemulsion exhibited a hydrodynamic diameter of approximately 98 nm and a zeta potential of -25 mV. The myrcene-based nanoemulsion displayed a hydrodynamic diameter of 118 nm and a zeta potential of -20 mV. Notably, both nanoemulsions demonstrated stability over 60 days, accompanied by controlled release properties and low toxicity towards HaCAT cells and Galleria mellonella larvae. Moreover, the nanoemulsions exhibited significant lethality against third-instar Aedes aegypti larvae at a concentration of 50 mg/L. In conclusion, the utilization of nanoemulsions encapsulating cymene and myrcene presents a promising avenue for overcoming the limitations associated with poor solubility and stability of monoterpenes. This study sheds light on the potential of the nanoemulsions as effective and environmentally friendly insecticides in the ongoing battle against mosquito-borne diseases.

Development and characterization of starch/PVA antimicrobial active films with controlled release property by utilizing electrostatic interactions between nanocellulose and lauroyl arginate ethyl ester

The two nanocellulose (nanofibrillated cellulose (NFC) and carboxylated nanofibrillated cellulose (C-NFC)) could interact with lauryl arginine ethyl ester hydrochloride (LAE) through electrostatic bonding. The zeta potential (absolute value) of C-NFC (−27.80 mV) was higher than that of NFC (−10.07 mV). The starch/polyvinyl alcohol active films with controlled release property by utilizing electrostatic interactions between nanocellulose and LAE were prepared and their properties were investigated. For incorporation of the NFC or C-NFC, the cross-section of the films became slightly uneven and some fibrils were observed, the films exhibited an increase in strength, while the film water vapor and oxygen barrier properties decreased. The release of LAE from the films to food simulants (10 % ethanol) decelerated with increasing of NFC or C-NFC. These might be mainly attributed to the enhanced electrostatic interaction between NFC or C-NFC and LAE. It demonstrated that nanocellulose with higher negative charges would exhibit stronger electrostatic interaction with LAE, thus slowing the release of LAE. The film with highest C-NFC content exhibited smallest inhibition zone among LAE-containing films, which was related with its slowest release rate of LAE. It showed a great prospect to develop controlled release active packaging films by utilizing electrostatic interactions between substances.

Rosmarinic Acid Liposomes Downregulate Hepcidin Expression via BMP6-SMAD1/5/8 Pathway in Mice with Iron Overload.

The objective of this study is to examine the potential protective effect of rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on hepatic damage induced by iron overload. The characteristics, stability, and release of RosA-LIP in vitro were identified. The mice were randomly assigned to five groups: Control, Model, Model+DFO (DFO), Model+RosA (RosA), and Model+RosA-LIP (RosA-LIP). The iron overload model was induced by administering iron dextran (i.p.). The DFO, RosA, and RosA-LIP groups received iron dextran and were subsequently treated with DFO, RosA, and RosA-LIP for 14 days. We developed a novel formulation of RosA-LIP that exhibited stability and controlled release properties. Firstly, RosA-LIP improved liver function and ameliorated pathological changes in a mouse model of iron overload. Secondly, RosA-LIP demonstrated the ability to enhance the activities of T-SOD, GSH-Px, and CAT, while reducing the levels of MDA and 4-HNE, thereby effectively mitigating oxidative stress damage induced by iron overload. Thirdly, RosA-LIP reduced hepatic iron levels by downregulating FTL, FTH, and TfR1 levels. Additionally, RosA-LIP exerted a suppressive effect on hepcidin expression through the BMP6-SMAD1/5/8 signaling pathway. Furthermore, RosA-LIP upregulated FPN1 expression in both the liver and duodenum, thereby alleviating iron accumulation in these organs in mice with iron overload. Notably, RosA exhibited a comparable iron chelation effect, and RosA-LIP demonstrated superior efficacy in mitigating liver damage induced by excessive iron overload. RosA-LIP exhibited favorable sustained release properties, targeted delivery, and efficient protection against iron overload-induced liver damage. A schematic representation of the proposed protective mechanism of rosmarinic acid liposome during iron overload. Once RosA-LIP is transported into cells, RosA is released. On the one hand, RosA attenuates the BMP6-SMAD1/5/8-SMAD4 signaling pathway activation, leading to inhibiting hepcidin transcription. Then, the declined hepcidin contacted the inhibitory effect of FPN1 in hepatocytes and duodenum, increasing iron mobilization. On the other hand, RosA inhibits TfR1 and ferritin expression, which decreases excessive iron and oxidative damage.

Nicotinamide Loaded Chitosan Nanocomplex Shows Improved Anticancer Potential: Molecular Docking, Synthesis, Characterization and In vitro Evaluations

Abstract: This study aimed to prepare and characterize chitosan nanoparticles encapsulating a nicotinamide derivative (Ni-CS-NP). Additionally, the therapeutic effectiveness, cytotoxicity, selectivity, and immunomodulatory properties of Ni-CS-NP were evaluated in human breast and colon cancer cell lines. Chitosan nanoparticles have shown potential as drug delivery carriers due to their biocompatibility and controlled release properties. Encapsulating a nicotinamide derivative further enhances the therapeutic potential of these nanoparticles. Computational studies were employed to validate the binding interactions, providing crucial insights into the formulation's stability and effectiveness. The primary objective was to assess the cytotoxicity and safety profiles of Ni-CS-NP in human cancer cell lines. Moreover, this study aimed to investigate the specific mechanisms underlying its cytotoxic effects, including its impact on cell cycle progression, apoptosis induction, and immunomodulation. Ni-CS-NP were synthesized using the ionic gelation method and characterized using Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermo gravimetric analysis. The cytotoxicity was evaluated in breast and colon cancer cell lines through the MTT assay. Selectivity indices were calculated to determine the safety profiles. The inhibition of VEGFR-2, induction of apoptosis, cell cycle disruption, and immunomodulatory effects were assessed through molecular assays. Computational analysis demonstrated favorable binding interactions through the Ni-CS-NP complex. The characterization studies confirmed the successful synthesis of Ni-CS-NP with well-defined structural and thermal properties. Ni-CS-NP exhibited remarkable cytotoxicity with a superior safety profile against MCF7 and HCT 116 cell lines showing IC50 values of 2.32 and 2.70 μM, respectively, surpassing sorafenib's efficacy (IC50 = 4.12 and 7.55 μM, respectively). Additionally, Ni-CS-NP effectively inhibited VEGFR-2, induced both early and late apoptosis, and disrupted the cell cycle progression in MCF7 cells. Notably, Ni-CS-NP demonstrated significant immunomodulatory effects by reducing TNF-α and IL-2 levels compared to dexamethasone. The encapsulation of a nicotinamide derivative within chitosan nanoparticles (Ni-CS-NP) through the ionic gelation method proved successful. Ni-CS-NP displayed potent cytotoxicity, superior safety profiles, and promising immunomodulatory effects in human breast cancer cells. These findings highlight the potential of Ni-CS-NP as a novel therapeutic agent for breast cancer treatment, warranting further investigation for clinical applications.

Raspberry-like PLA/PGS biodegradable microparticles with urethane linkages: Unlocking tailored release of magnesium ions and oxygen for bone tissue engineering

Designing biodegradable microparticles with finely controlled release properties for tissue engineering systems remains a significant scientific challenge. This study introduces a novel approach by fabricating urethane-linked PLA/PGS microparticles loaded with magnesium peroxide. The microparticles offer potential applications in bone tissue engineering due to their ability to provide a controlled release of oxygen and magnesium ions while maintaining physiological pH. The PGS pre-polymer was synthesized via polycondensation and characterized using FTIR, 1H NMR, and GPC. Microparticle morphology transformed from smooth to raspberry-like upon incorporation of PGS, as observed by SEM. Microparticle size was tuned by varying PGS and PLA concentrations. FTIR analysis confirmed the successful formation of urethane links within the microparticles. MgO2-loaded PLA/PGS microparticles exhibited sustained release of dissolved oxygen and magnesium ions for 21 days while maintaining physiological pH better than PLA microparticles. Cell viability assays confirmed microparticle cytocompatibility, and ALP and Alizarin red assays demonstrated their ability to induce osteogenic differentiation. These findings highlight the potential of pH-controlled MgO2-loaded microparticles as an effective system for bone tissue engineering. In conclusion, this study presents a novel approach to designing biodegradable microparticles with adjustable release properties for bone tissue engineering. The urethane-based MgO2-loaded microparticles provide controlled release of oxygen and magnesium ions and regulate the environment’s pH, making them a promising system for bone tissue engineering applications.