pH-sensitive Release Research Articles

Synthesis of photo-responsive κ-carrageenan-based hydrogels for drug delivery application.

Natural polymer-based hydrogels may act as versatile platforms in controlled drug delivery. In this regard, photoactive κ-carrageenan (κ-Crg) hydrogels modified with cinnamate (CN) groups are developed for pH-sensitive release of drugs. κ-Crg-CN derivatives containing 17 %, 33 %, and 49 % cinnamate contents, named κ-Crg-CN1, κ-Crg-CN2, and κ-Crg-CN3, respectively, are prepared and cross-linked by UV-induced [2π + 2π] cycloaddition. Fourier transform infrared (FTIR) spectroscopy, Nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and elemental analysis are conducted for structural characterization. Rheological measurements showed an increased degree of cross-linking density with the increase in cinnamate content, as represented by storage modulus (G') values of 226 Pa for κ-Crg-CN1, 631 Pa for κ-Crg-CN2, and 967 Pa for κ-Crg-CN3. Also, drug encapsulation efficiency using theophylline was significantly improved: 48 % for κ-Crg-CN1, 63 % for κ-Crg-CN2, and 85 % for κ-Crg-CN3. Theophylline release studies showed that at pH 1.2, it was slower than pH 7.2, with a release rate inversely proportional to the cinnamate content. Kinetic modeling showed a non-Fickian transport mechanism that involved diffusion and polymer relaxation. These results show that κ-Crg-CN hydrogels can act as tunable, pH-sensitive drug delivery systems, with mechanical properties and release profiles precisely tailored by cinnamate functionalization for applications in controlled drug delivery.

Antitumor Cream: Transdermal Hydrogel Containing Liposome-Encapsulated Ruthenium Complex for Infrared-Controlled Multimodal Synergistic Therapy.

A transdermal drug delivery cream, which is non-invasive and painless, containing a liposome-encapsulated Ru(II) complex (LipoRu) is created for the treatment of skin cancer. This formulation capitalizes on the synergistic antitumor effects of two-photon excited photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. LipoRu exhibits effective tumor accumulation, efficient cellular uptake, pH-sensitive and infrared-accelerated release, and dual localization to the nucleus and mitochondria. The released Ru(II) complexes within cells exert multiple antitumor mechanisms, such as DNA topoisomerase and RNA polymerase inhibition, Type I and II PDT, PTT, DNA photodamage, and apoptosis and ferroptosis induction. The biodistribution and therapeutic efficacy of LipoRu in vivo are systematically compared via three distinct administration routes: intratumoral injection, intravenous injection, and transdermal delivery through topical cream application. The positive therapeutic effects of the LipoRu cream fabricated here in subcutaneous tumor-bearing mice offer optimistic potential for the painless and non-invasive treatment of both early-stage and advanced skin cancers, as well as superficially located solid tumors.

The interaction of cinchonine and immunoglobulin G and the development of a nanocomplex with improved anti-breast cancer activity

In this study we evaluated the interaction of cinchonine (Cin) and immunoglobulin G (IgG). Then, Cin-IgG nanoparticles (NPs) were synthesized and characterized. Finally, the anticancer effects of free Cin and Cin-IgG NPs on MCF-7 breast cancer (BC) cells were evaluated. The results of spectroscopy measurements show that the IgG-Cin complex's quenching mechanism is static and the structure of IgG was partially changed following interaction with Cin. The prepared Cin-IgG NPs display a hydrodynamic size of 190 nm with a PDI of 0.269, a zeta potential of −38.05 mV, an EE% of 72.38 %, a LC% of 5.41 %, and a pH-sensitive drug release behavior. In the cellular assay, it was found that the calculated IC50 concentrations of Cin, IgG NPs, and Cin-IgG NPs are 66.4 ± 5.39, >100, and 29.2 ± ± 4.11 μM, respectively, in MCF-7 BCE cells. Finally, Cin-IgG NPs induce a greater effect on the overexpression of the Bax/Bcl-2 ratio and downregulation of PI3K/p-AKT compared to the free drug. In conclusion, this study shows that Cin has the potential to bind IgG as a human plasma protein, and its complexation into a NP form with IgG can boost its anti-BC effects.

Rational design of biofunctional borosilicate glasses: Tuning therapeutic ions and in vitro biological evaluation

Introducing therapeutic ions of bioactive glasses as scaffolds is appealing due to attractive architectural biomimicry of bone extracellular matrix and adjustable composition accompanied with soluble ions released for bone regeneration and remodeling. Herein, this strategy was expanded to develop biocomposites of borosilicate glasses incorporated with different therapeutic ions using a facile sol-gel technique and cetyltrimethylammonium bromide (CTAB) as the template. Mediating therapeutic ions (i.e., copper/selenium/strontium at the same content) in a SiO2–B2O3–CaO–P2O5 glassy system is effective and simple method for modifying structural-morphological features and physicochemical characteristics of the bioglasses. In vitro bioactivity measurements revealed that strontium/selenium-doped borosilicate glasses had faster apatite-formation ability compared to copper-doped borosilicate glasses. For in vitro drug release, rhodamine B (RB) storage and release showed that copper-doped borosilicate glasses had high storage capacities (79.42 %) and cumulated release rate (87.18 % at pH 1.2), and demonstrated sustained pH-sensitive drug release patterns. The RB release profiles also showed two-stage release mechanism following the Korsmeyer-Peppas model during the first release stage (the first 24 h), and the Weibull model during next stage (beyond 24 h). In subsequent bacterial studies, copper-doped borosilicate glasses could effectively inhibit (100 % at 2.5 mg mL−1) Escherichia coli and Staphylococcus aureus colonization. In vitro biocompatibility assays also showed that all bioglass samples were biocompatible. According to obtained data, present bicomponent composite strategy may pave the way for the design of bioglasses doped with functional ions tailored to induce biological activity that can heal infectious bone in vivo.

Interaction of Arginine-Rich Surfactant-like Peptide Nanotubes with Liposomes.

The interaction of the surfactant-like peptide (SLP) R3L12 bearing three cationic arginine residues with model liposomes is investigated in aqueous solution at various pH values, under conditions for which the SLP self-assembles into nanotubes. The structure of liposomes of model anionic lipid DPPG [1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol)], or zwitterionic lipid DPPE [1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine] is probed using small-angle X-ray scattering and cryogenic-transmission electron microscopy. The unilamellar vesicles of DPPG are significantly restructured in the presence of R3L12, especially at low pH, and multilamellar vesicles of DPPE are also restructured under these conditions. The SLP promotes the release of cargo encapsulated in the vesicles as probed by calcein fluorescence, with notably higher release for anionic DPPG vesicles. Laurdan fluorescence experiments to probe membrane fluidity (lipid chain ordering) show that R3L12 destabilizes the lipid gel phase, especially for anionic DPPG. This model nanotube-forming SLP has promise as a pH-sensitive release system for vesicle-encapsulated cargo.

Bone Healing via Carvacrol and Curcumin Nanoparticle on 3D Printed Scaffolds.

Carvacrol is a potent antimicrobial and anti-inflammatory agent, while curcumin possesses antioxidant, anti-inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D-printedcalcium phosphate (CaP)scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin-loaded nanoparticles (CC-NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC-NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH-sensitive release mechanism. In vitro studies demonstrate a 1.4-fold increase in osteoblast cell viability with CC-NP treatment. CC-NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9-fold. The antibacterial efficacy of CC-NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.

Metal Polyphenol Nanoparticle-Based Chemo/Ferroptosis Synergistic Therapy for the Treatment of Oral Squamous Cell Carcinoma.

Despite the use of surgical resection and chemotherapy in the clinical treatment of oral squamous cell carcinoma (OSCC), the 5-year survival rates of advanced patients are low. Therefore, more efficient strategies are urgently needed. Herein, a chemo/ferroptosis synergistic therapeutic system-DMEFe nanoparticles (NPs) is established for the treatment of OSCC. To create this system, the chemotherapeutic agent doxorubicin (DOX) was loaded into mesoporous silica nanoparticles and further coated with a pH-sensitive metal polyphenol (iron ion and epigallocatechin gallate). These nanoparticles displayed excellent pH-sensitive drug-control release properties, and the release ratio of DOX at pH 5.5 was twice as high than that at pH 7.4. Additionally, DMEF NPs were effectively taken up by the OSCC cell line SSC-25, which greatly impeded the proliferation of these cells. Notably, these nanoparticles increased the intracellular level of reactive oxygen species and effectively exhibited cytotoxity effects. The mechanistic results proved that DMEFe NPs regulated the expression of ferroptosis-related genes to induce ferroptosis of SSC-25 cells. Eventually, this chemo/ferroptosis therapeutic system exhibited remarkable antitumor effects and provided a novel strategy for the treatment of OSCC.

Preparation of ternary hybridized chitosan microspheres with photothermal effect for pH-sensitive long-lasting controlled release system and its release mechanism

To enhance the effective utilization of drugs and diminish the number of medications for patients, it is vital to investigate controlled long-acting drug release systems and their release mechanisms. In this study, chitosan microspheres were synthesized by cross-linking pH-sensitive Schiff bases, and Zif-8, a pH-sensitive component, was encapsulated within them. Furthermore, MXene was incorporated as a third component to augment the strength and photothermal synergistic characteristics of the microspheres. By adjusting the ratio of each component, the optimal ternary heterogeneous functional pH-controllable long-lasting drug release system was obtained. The optimal coating and the most effective adsorption-release effect were achieved. The release mechanism was examined under varying pH and temperature conditions. The release process was found to be divided into three stages. The initial phase was predominantly governed by the Fick diffusion mechanism, whereas the subsequent phases were primarily regulated by the pH-induced co-decomposition of CS and Zif-8, and the individual decomposition of CS, respectively.The drug was observed to be released in a linear manner during the latter two stages of the experiment. This was evidenced by the persistent release of ciprofloxacin hydrochloride in response to pH changes, and further supported by the results of tests on its antimicrobial properties. The drug release persisted for over three days at pH 5.4 and could be utilized repeatedly, exhibiting promising applications in drug delivery. Moreover, the drug's photothermal properties offer the possibility of developing synergistic therapeutic programs.

Responsive Magnetic Particle Imaging Tracer: Overcoming "Always-On" Limitation, Eliminating Interference, and Ensuring Safety in Adaptive Therapy.

Magnetic particle imaging (MPI) has emerged as a novel technology utilizing superparamagnetic nanoparticles as tracers, essential for disease diagnosis and treatment guidance in preclinical animal models. Unlike other modalities, MPI provides high sensitivity, deep tissue penetration, and no signal attenuation. However, existing MPI tracers suffer from "always-on" signals, which complicate organ-specific imaging and hinder accuracy. To overcome these challenges, we have developed a responsive MPI tracer using pH-responsive PdFe alloy particles coated with a gatekeeper polymer. This tracer exhibits pH-sensitive Fe release and modulation of the MPI signal, enabling selective imaging with a higher signal-to-noise ratio and intratumoral pH quantification. Notably, this responsive tracer facilitates subtraction-enhanced MPI imaging, effectively eliminating interference from liver uptake and expanding the scope of abdominal imaging. Additionally, the tracer employs a dual-function mechanism for adaptive cancer therapy, combining pH-switchable enzyme-like catalysis with dual-key co-activation of ROS generation, and Pd skeleton that scavenges free radicals to minimize Fe-related toxicity. This advancement promises to significantly expand MPI's applicability in diagnostics and therapeutic monitoring, marking a leap forward in imaging technology.

Pimozide-loaded nanostructured lipid carriers: Repurposing strategy against lung cancer.

This study aimed to repurpose pimozide (PMZ) by incorporating it into nanostructured lipid carriers (NLC) using a modified melting emulsion ultrasonication method. We employed stearic and oleic acids in a 1:1 ratio as lipids, with Tween 80 and PEG 4000 as surfactants. The formulation was analyzed for particle size, zeta potential, and encapsulation efficiency. Transmission electron microscopy (TEM) was used to confirm the spherical shape of the particles. The release profile of PMZ-NLC was evaluated under different pH conditions, and anticancer activity was tested on A549 cell lines. The PMZ-NLC exhibited an average particle size of 136 ± 2.9 nm, a zeta potential of -25.1 ± 0.9 mV, and an encapsulation efficiency of 86% ± 11. TEM confirmed the spherical shape of the NLCs. PMZ release from PMZ-NLC was pH-sensitive, enhancing tumor targeting. IC50 values were 16.5 μM for free PMZ and 12.9 μM for PMZ-NLC after 72 h. PMZ-NLC demonstrated improved anticancer activity compared to free PMZ, suggesting that encapsulation enhances the drug's effectiveness. The pH-sensitive release profile supports its potential for targeted therapy in lung cancer. PMZ-NLC showed potential as a safe and effective strategy for lung cancer treatment. Further investigation is warranted to evaluate its in vivo efficacy, long-term safety, and clinical application.

Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy.

Carboplatin (Cp) is a potent chemotherapeutic agent, but its effectiveness is constrained by its associated side effects. Frankincense, an oleo-gum resin from the Boswellia sacra tree, has demonstrated cytotoxic activity against cancer cells. This study explored the synergistic potential of nanoparticles formulated from Boswellia sacra methanolic extract (BME), to enhance the therapeutic efficacy of Cp at reduced doses. Nanoparticles were prepared via the nanoprecipitation method, loaded with Cp, and coated with positively charged chitosan (CS) for enhanced cell interaction, yielding Cp@CS/BME NPs with an average size of 160.2 ± 4.6 nm and a zeta potential of 12.7 ± 1.5 mV. In vitro release studies revealed a pH-sensitive release profile, with higher release rates at pH 5.4 than at pH 7.4, highlighting the potential for targeted drug delivery in acidic tumor environments. In vitro studies on HT-29 and Caco-2 colorectal cancer cell lines demonstrated the nanoformulation's ability to significantly increase Cp uptake and cytotoxic activity. Apoptosis assays further confirmed increased induction of cell death with Cp@CS/BME NPs. Cell-cycle analysis revealed that treatment with Cp@CS/BME NPs led to a significant increase in the sub-G1 phase, indicative of enhanced apoptosis, and a marked decrease in the G1-phase population coupled with an increased G2/M-phase arrest in both cell lines. Further gene expression analysis demonstrated a substantial downregulation of the anti-apoptotic gene Bcl-2 and an upregulation of the pro-apoptotic genes Bax, PUMA, and BID following treatment with Cp@CS/BME NPs. Thus, this study presents a promising and innovative strategy for enhancing the therapeutic efficacy of chemotherapeutic agents using naturally derived ingredients while limiting the side effects.

Ionic liquid combined with cationic liposome co-delivers microphthalmia-associated transcription factor small interfering RNA to regulate melanogenesis

Suppressing allele-specific genes using small interfering RNAs (siRNAs) can effectively whiten skin by influencing cellular gene and protein expression. Topical delivery of siRNA is a promising alternative to injections for RNA interference. However, the barrier function of the skin hinders the effective penetration of siRNA. Here, we report, a novel approach to achieve the transdermal delivery of effective siRNA doses using a complementary synergistic strategy of an ionic liquid (IL) and cationic liposome (CL). Microphthalmia-associated transcription factor (MITF) siRNA molecules were formed through electrostatic adsorption of the IL and CL to form positively charged nanocomposites, which were named IL-CL/p-siM. IL-CL/p-siM has a particle size of 171.47 nm, ζ-potential of 29.94 mV, high encapsulation rate of 92.11 %, and pH-sensitive release properties. In vitro studies on porcine skin confirmed the additive/synergistic effect of this strategy in enhancing epidermal and dermal penetration. This combination enabled superior transfection efficiency and cell viability while inhibiting melanin synthesis in skin melanocytes by downregulating the expression of genes downstream of MITF, namely tyrosinase-related protein-1, tyrosinase, and tyrosinase-related protein-2, which are associated with the melanocortin 1 receptor. We also conducted clinical studies that demonstrated its potential in treating melasma and its anti-melanotic efficacy. To summarize, IL-CL/p-siM represents a simple, personalized, and scalable platform for effective local delivery of siRNA to treat skin complications.

PH-RESPONSIVE INTERPENETRATING POLYMER NETWORK HYDROGEL MICROBEADS OF POLYACRYLAMIDE-G-GUM KONDAGOGU AND SODIUM ALGINATE FOR GASTROPROTECTIVE DRUG DELIVERY: IN VITRO-IN VIVO CHARACTERIZATIONS

The present work aims to design interpenetrating polymer network (IPN) mediated hydrogel microbeads of hydrolyzed polyacrylamide-g-gum kondagogu (H-pAAm-g-GK) and sodium alginate (SA) for pH-sensitive gastroprotective drug delivery of diclofenac sodium (DS). In brief, the pAAm-g-GK was prepared using microwave irradiation, followed by conversion into a pH-sensitive polymer (H-pAAm-g-GK) using alkaline hydrolysis. Then, DS-loaded IPN microbeads were made utilizing an ionotropic gelation method using Ca+2 ions and glutaraldehyde (GA) as a crosslinking agent. After this, different characterizations, such as FT-IR, DSC, PXRD, swelling analysis, drug entrapment, drug release study, in vivo anti-inflammatory activity, etc., were performed. The amorphous state of DS in the microbeads was validated by thermograms and diffractograms, whereas SEM analysis confirmed the spherical shape of the obtained DS-loaded H-pAAm-g-GK@SA mediated microbeads. The pulsatile swelling analysis assured the H-pAAm-g-GK@SA mediated microbeads showed significantly increased swelling as the pH switched from 1.2 to 7.4. Additionally, the microbeads exhibit a 15% DS release in a pH 1.2 buffer medium, while a substantial 94% of the drug was released in a pH 7.4 buffer. It assured the DS release was drastically augmented as the pH of the surrounding medium was switched from acidic to alkaline. Principally, the COOH- groups of hydrogels offer ionization at higher pH levels, wherein the osmotic pressure within the microbeads rises, resulting in more swelling and higher drug release. Finally, the in vivo anti-inflammatory activity assured pH-sensitive sustained release of DS. In conclusion, the H-pAAm-g-GK@SA mediated pH-sensitive IPN hydrogel microbeads show potential in the design of gastroprotective oral delivery systems for DS. In the future, H-pAAm-g-GK can be used for the design of pH-sensitive IPN hydrogel microbeads for targeted delivery.

Harnessing nanotechnology for breast cancer management: UiO-66 (NH2) metal-organic frameworks functionalized with chitosan and folic acid for the efficient delivery of doxorubicin

Cancer is a leading cause of morbidity globally, which could be due to a lack of effective treatments. The inherent inadequacies of traditional medicines in terms of tumour selectivity and undesired toxicity urge us to seek alternative therapies to address these drawbacks. Metalorganic frameworks (MOFs) have been synthesized for use in drug delivery systems (DDS) because of their improved porosity and larger specific surface area. In this research, UiO-66-NH2 MOFs were synthesized via a solvothermal technique and functionalized with chitosan-folic acid (CS-FA) as a DDS for targeted doxorubicin (DOX) delivery. The MOF nanoplatforms were characterized via different techniques, including FTIR, PXRD, BET, TEM, DLS, TGA, SEM, and TGA. Remarkably, compared with the unmodified MOF, UiO-DOX@CS-FA delayed DOX release due to a gated effect induced by the CS-FA surface coating. pH-sensitive DOX release was observed, where 39.76 % of the drug was released in the tumour-mimicking pH of 5.2, whereas 5.84 % of the drug was released at physiological pH (7.4). In vitro cellular toxicity and uptake investigations demonstrated that UiO-DOX@CS-FA is a highly effective targeted DDS against MCF-7 breast cancer cells. Furthermore, in vivo toxicity studies in Wistar rats revealed no evidence of serious adverse effects. The variety of pharmacokinetic characteristics tested indicated that the bioavailability and release kinetics of DOX improved. Our findings lay the groundwork for the development and production of novel polymer conjugate-based nanoparticles with increased tumour-targeting efficacy.

Novel targeting liposomes with enhanced endosomal escape for co-delivery of doxorubicin and curcumin

Effective endosomal escape is crucial for enhancing the efficiency of nanodrug delivery systems. In this study, we developed a novel liposomal system utilizing acid-sensitive N-(3-amino-propyl) imidazole cholesterol (IM-Chol), specifically designed for the targeted co-delivery of doxorubicin (DOX) and curcumin (CUR) to hepatocellular carcinoma (HCC). Designated as GA-IM-LIP@DOX/CUR, this liposomal system incorporates glycyrrhetinic acid (GA) to improve target specificity toward HCC cells. Notably, both drugs exhibited pH-sensitive release profiles, facilitating precise drug release within acidic environments. Our investigation into cellular uptake demonstrated that modified liposomes, GA-IM-LIP@FITC and IM-LIP@FITC, achieved progressively enhanced intracellular accumulation of FITC compared to unmodified liposomes. Competitive inhibition assays utilizing free GA further validated the targeting efficacy of GA. Moreover, the GA-IM-LIP@FITC and IM-LIP@FITC groups exhibited rapid endosomal escape of FITC within the first two hours, in contrast to delayed escape observed in the LIP@FITC group, confirming that the protonation of IM-Chol promotes drug release into the cytosol. In vivo studies substantiated that GA-IM-LIP@DOX/CUR effectively inhibited tumor growth. This research provides significant insights into the design and functionality of the GA-IM-LIP@DOX/CUR liposomal system, underscoring its potential to enhance drug delivery strategies in the treatment of HCC.

An aerosol nanocomposite microparticle formulation using rifampicin-cyclodextrin inclusion complexes for the treatment of pulmonary diseases

Rifampicin (RIF) is commonly used in the treatment of tuberculosis (TB), a bacterium that currently infects one fourth of the world’s population. Despite the effectiveness of RIF in treating TB, current RIF treatment regimens require frequent and prolonged dosing, leading to decreased patient compliance and, ultimately, increased mortality rates. This project aims to provide an alternative to oral RIF by means of an inhalable spray-dried formulation. TB uses alveolar macrophages to hide and replicate until the cells rupture, further spreading the bacteria. Therefore, delivering RIF directly to the lungs can increase the drug concentration at the site of infection while reducing off-site side effects. Cyclodextrin (CD) was used to create a RIF-CD inclusion complex to increase RIF solubility and biodegradable RIF-loaded NP (RIF NP) were developed to provide sustained release of RIF. RIF NP and RIF-CD inclusion complex were spray dried to form a dry powder nanocomposite microparticles (nCmP) formulation (RIF-CD nCmP). RIF-CD nCmP displayed appropriate aerosol dispersion characteristics for effective deposition in the alveolar region of the lungs (4.0 µm) with a fine particle fraction of 89 %. The nCmP provided both a burst release of RIF due to the RIF-CD complex and pH-sensitive release of RIF due to the RIF NP incorporated into the formulation. RIF-CD nCmP did not adversely affect lung epithelial cell viability and RIF NP were able to effectively redisperse from the nCmP after spray drying. These results suggest that RIF-CD nCmP can successfully deliver RIF to the site of TB infection while providing both immediate and sustained release of RIF. Overall, the RIF-CD nCmP formulation has the potential to improve the efficacy for the treatment of TB.

Synthesis and characterization of a novel dual sensitive iron nanoparticles incorporated Schiff base composite hydrogel for diabetic wound healing therapy

Chronic wounds in diabetic patients deteriorate into multiple infections. A multifunctional transdermal material with high self-healing ability, remodeling capability, antibacterial and radicle scavenging activity, and an excellent multi-sensitive carrier was needed to promote wound healing. For that, Oxidized Cellulose (OC) and gelatin (GLN) are selected to construct a dual drug-loaded Schiff base hydrogel with iron nanoparticle (IONPS) incorporation for the controlled and sustained release of Insulin (INS) and Metfomin (MET), which synergistically promote wound repair. The INS/MET-IONPS-OC/GLN hydrogel drug payload was characterized using FT-IR, XRD, DLS, ZETA, TG, FE-SEM, TEM, and VSM analysis. The high drug loading and encapsulation efficiency were 93.20 % and 98.8 % for INS and 90.2 % and 95.1 % for MET, respectively. The temperature-sensitive drug release (92.0 % of INS and 90.0 % of MET) percentage is much better than the pH-sensitive drug release (83.5 % of INS and 80.2 % of MET). Above 90.0 % viability in MTT and apoptosis assay reveals the nontoxic nature of the INS/MET-IONPS-OC/GLN towards L929 normal cell lines. The zone of inhibition value of 12 and 15 mm in gram-negative bacteria reveals the anti-bacterial effect. The antioxidant activity of the carrier shields the cells against reactive oxygen species promotes healing rate ensures by DPPH assay.The cell proliferation and angiogenesis were confirmed by scratch assay on L929 cell lines in diabetic and non-diabetic conditions, showing the healing ability of the INS/MET-IONPS-OC/GLN hydrogel.

Biocompatible PAMAM-PLGA-PCL Nanocarrier for Efficient Curcumin Delivery to Lung Cancer Cells: In Vitro Studies.

Lung cancer, as the leading cause of death among other types of cancer, has a high rate of incidence throughout the world. Although conventional modalities, like chemotherapy, have been applied for the inhibition of this cancer, they have not led to the suppression of lung cancer owing to their deficiencies. Thus, we developed a novel polylactic-co-glycolic acid (PLGA)-polyamidoamine G4 (PAMAM G4)-polycaprolactone (PCL) nanocarrier for efficient delivery of curcumin (Cur) to A549 lung cancer cells. The synthesized nanocarrier was characterized by applying analytical techniques, FT-IR, DLS, TEM, and TGA. Successful synthesis, nano-size diameter (40-80 nm), near neutral surface charge (8.0 mV), and high drug entrapment (11.5 %) were measured for the nanocarrier. Controlled (about 5 folds within first 2 h) and pH-sensitive (2-3 folds faster within first hours) Cur release observed for PLGA-PAMAM-PCL-Cur. Cell viability test (MTT assay) indicated the high capability of nanocarrier in suppression of A549 cancer cells (21 % viability after 24 h of treatment with 200 nM) while did not result in toxicity on MSC normal cells. The IC50 observed for 50 nM at 24 h of post-treatment in A549 cells. The qRT-PCR technique indicated inducing the expression of apoptotic genes (Caspase9 and Bax) by 6-8 folds and suppressing anti-apoptotic gene (Bcl2) by 7 folds. ROS considerably increased in cancer cells as well. This nanocarrier would be a promising drug delivery system against lung cancer.

Efficient delivery of curcumin by functional solid lipid nanoparticles with promoting endosomal escape and liver targeting properties

In the realm of intracellular drug delivery, overcoming the barrier of endosomal entrapment stands as a critical factor influencing the effectiveness of nanodrug delivery systems. This study focuses on the synthesis of an acid-sensitive fatty acid derivative called imidazole-stearic acid (IM-SA). Leveraging the proton sponge effect attributed to imidazole groups, IM-SA was anticipated to play a pivotal role in facilitating endosomal escape. Integrated into the lipid core of solid lipid nanoparticles (SLNs), IM-SA was paired with hyaluronic acid (HA) coating on the surface of SLNs loading with curcumin (CUR). The presence of IM-SA and HA endowed HA-IM-SLNs@CUR with dual functionalities, enabling the promotion of endosomal escape, and specifical targeting of liver cancer. HA-IM-SLNs@CUR exhibited a particle size of ∼228 nm, with impressive encapsulation efficiencies (EE) of 87.5 % ± 2.3 % for CUR. Drugs exhibit significant pH sensitive release behavior. Cellular experiments showed that HA-IM-SLN@CUR exhibits enhanced drug delivery capability. The incorporation of IM-SA significantly improved the endosomal escape of HA-IM-SLN@CUR, facilitating accelerated intracellular drug release and increasing intracellular drug concentration, exhibiting excellent growth inhibitory effects on HepG2 cells. Animal experiments revealed a 3.4-fold increase in CUR uptake at the tumor site with HA-IM-SLNs@CUR over the free CUR, demonstrating remarkable tumor homing potential with the tumor growth inhibition rate of 97.2 %. These findings indicated the significant promise of HA-IM-SLNs@CUR in the realm of cancer drug delivery.

Nicardipine-chitosan nanoparticles alleviate thioacetamide-induced acute liver injury by targeting NFκB/NLRP3/IL-1β signaling in rats: Unraveling new roles beyond calcium channel blocking

Liver inflammatory diseases are marked by serious complications. Notably, nicardipine (NCD) has demonstrated anti-inflammatory properties, but its benefits in liver inflammation have not been studied yet. However, the therapeutic efficacy of NCD is limited by its short half-life and low bioavailability. Therefore, we aimed to evaluate the potential of NCD-loaded chitosan nanoparticles (ChNPs) to improve its pharmacokinetic profile and hepatic accumulation. Four formulations of NCD-ChNPs were synthesized and characterized. The optimal formulation (NP2) exhibited a mean particle diameter of 172.6 ± 1.94 nm, a surface charge of +25.66 ± 0.93 mV, and an encapsulation efficiency of 88.86 ± 1.17 %. NP2 showed good physical stability as a lyophilized powder over three months. It displayed pH-sensitive release characteristics, releasing 77.15 ± 5.09 % of NCD at pH 6 (mimicking the inflammatory microenvironment) and 52.15 ± 3.65 % at pH 7.4, indicating targeted release in inflamed liver tissues. Pharmacokinetic and biodistribution studies revealed that NCD-ChNPs significantly prolonged NCD circulation time and enhanced its concentration in liver tissues compared to plain NCD. Additionally, the study investigated the protective effects of NCD-ChNPs in thioacetamide-induced liver injury in rats by modulating the NFκB/NLRP3/IL-1β signaling axis. NCD-ChNPs effectively inhibited NFκB activation, reduced NLRP3 inflammasome activation, and subsequent release of IL-1β, which correlated with improved hepatic function and reduced inflammation and oxidative stress. These findings highlight the potential of NCD-ChNPs as a promising nanomedicine strategy for the treatment of liver inflammatory diseases, warranting further investigation into their clinical applications, particularly in hypertensive patients with liver inflammatory conditions.