pH-dependent Release Research Articles

Enhanced Oral Efficacy of Semaglutide via an Ionic Nanocomplex with Organometallic Phyllosilicate in Type 2 Diabetic Rats.

This study aimed to develop an effective oral formulation of semaglutide, a glucagon-like peptide-1 receptor agonist, using an organometallic phyllosilicate-based colonic delivery system. The core nanocomplex (AMP-Sema) of 3-aminopropyl-functionalized magnesium phyllosilicate (AMP) and semaglutide was prepared via electrostatic interactions. Subsequently, AMP-Sema was coated with a polymer showing pH-dependent solubility (Eudragit® S100) for preferential colonic delivery. The surface-coated nanoparticles (EAMP-Sema) showed a narrow size distribution, and the encapsulated semaglutide maintained its conformational stability. The pH-dependent drug release property of EAMP-Sema yielded around 20% and 62% drug release at pH 1.2 and 7.4, respectively. The nanoparticles exhibited significantly decreased size and surface charge at pH 7.4, which indicated the pH-dependent dissolution of the coating layer. Furthermore, EAMP-Sema effectively improved the membrane permeability and metabolic stability of semaglutide in the gastrointestinal tract. It protected the encapsulated drugs from proteolysis in simulated intestinal fluids and increased drug transport by 2.5-fold in Caco-2 cells. Consequently, orally administered EAMP-Sema (equivalent to 8 mg/kg of semaglutide) showed significant therapeutic benefits, yielding effective glycemic control and weight loss in high-fat diet/streptozotocin (40 mg/kg)-induced type 2 diabetic rats. These results demonstrate that EAMP-Sema could improve the efficacy of orally administered semaglutide by enhancing the GI stability and cellular uptake of protein drugs.

Controlled release and mitigation of the volatility of 2,4-dichlorophenoxyacetic acid herbicide using biopolymer microparticles as carriers

Herbicides play a crucial role in sustaining crop productivity. However, growing concerns about their impact on both the environment and human health necessitate strategies to improve their effectiveness and suitability. Of particular concern are volatile herbicides like 2,4-dichlorophenoxyacetic acid (2,4-D), which not only pose risks to the environment but also impact neighboring crops. To deal with this, we developed a microparticle system comprising chitosan ionotropically crosslinked with tripolyphosphate anions to encapsulate 2,4-D. Optimization of the biopolymer/herbicide ratio yielded remarkable encapsulation efficiencies (> 95 %) and loading capacities (> 32 %). Characterization analyses revealed interactions between 2,4-D and chitosan, resulting in microparticles (1.7 ± 0.4 µm) with distinct thermal, morphological, and surface charge properties compared to pristine microparticles. In vitro experiments demonstrated pH-dependent release kinetics, with optimal release observed under neutral conditions. A 94 % release was achieved at pH 7 after 37 days, driven by sustainable diffusional processes. This ability to control the release of 2,4-D was pivotal in controlling its volatilization. As demonstrated, the volatilization rate for 2,4-D encapsulated within the chitosan microparticles was found to be 64 times lower compared to the commercial herbicide. This encapsulation approach presents an innovative strategy for regulating the presence of 2,4-D in agricultural settings, effectively tackling its significant volatility concerns.

Preparation and characterization of Chitosan based edible coating containing vanillin/HPβCD inclusion complex and its application in chicken preservation

In order to develop the plant-derived active substance vanillin, 2-hydroxypropyl-β-cyclodextrin was used to encapsulate vanillin, and a chitosan-based edible coating: vanillin-HPβCD/CH was developed for chicken preservation. First, vanillin was inserted into the internal cavity of HPβCD through an ultrasonic-assisted method to form vanillin/HPβCD-IC. The inclusion complex of vanillin/HPβCD-IC was demonstrated to be successfully synthesized by ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Through antibacterial testing, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), it was verified that inclusion improved the thermal stability of vanillin while retaining the antibacterial effect of vanillin. The release of vanillin from encapsulated particle exhibited pH-dependent slow controlled release, and can described by First order model. Subsequently, vanillin/HPβCD-IC was compounded with chitosan through a composite film-forming method to prepare an edible coating: vanillin-HPβCD/CH. By characterizing the performance of vanillin-HPβCD/CH, it was found that the addition of vanillin/HPβCD-IC can improve the stability, isolation hydrophobicity and antibacterial performance of the plastic wrap. Finally, vanillin-HPβCD/CH was applied to chicken preservation, and it was found that vanillin-HPβCD/CH could effectively extend the shelf life of chicken and maintain sensory quality by slowing down the rise in pH, preventing the proliferation of microorganisms, and inhibiting lipid oxidation. In summary, vanillin-HPβCD/CH is an edible coating with superior performance and a promising packaging material for chicken freshness preservation.

Co-axial electrosprayed RAD001-loaded polycaprolactone/polyvinyl alcohol core–shell particles for treating pediatric brain tumours

Core-shell particles composed of polycaprolactone/polyvinyl alcohol (PCL/PVA) with pH sensitive properties were successfully fabricated by co-axial electrospraying in which PVA and PCL formed the shell and core layers respectively. The core–shell structure was confirmed by FTIR, DSC and SEM analysis. No chemical interaction between PVA and PCL core–shell were observed in the FTIR analysis. The RAD001 loaded core–shell particles showed a sustained and pH dependent drug release and was assayed via our previously developed HPLC method. After indirect treatment of the PF-A cells with the core–shell particles for 24 h and 5 days a decrease in cell viability was observed. Additionally, a comparison was made with our previously developed nanoparticles containing 2 %PVA-14 %SOL®-0.6 % RAD001, for the cell viability study on ependymoma. Our findings show that optimised core–shell particles exerted a significant effect for the 24 h and 5 day treatment however further studies are required to ensure toxicity of the control core–shell particles with no drug is reduced. In comparison, the 2 %PVA-14 %SOL®-0.6 %RAD001 uniaxial electrosprayed nanoparticles also exerted a toxicity effect decreasing cell viability with no toxicity observed for the control nanoparticles as well. Such pH-sensitive core–shell particles, which can degrade effectively in either acidic or neutral condition, have great potential for application in the biomedical field.

Functionalized graphene oxide as a nanocarrier for delivering oridonin to improve anti-breast cancer cell activity.

In this study, a targeted nanocarrier was developed by functionalizing graphene oxide with polyethyleneimine and folic acid, intended for loading oridonin. The nanocarrier was successfully synthesized and characterized using an ultraviolet spectrum, Fourier transform infrared spectroscopy and scanning electron microscopy. The nanocarrier demonstrated a remarkable oridonin loading capacity, reaching 424.8μg/mg, as determined by ultra-high performance liquid chromatography. In vitro drug release experiments exhibited a pH-dependent release profile, with a higher cumulative release in an acidic environment. The release mechanism followed the Ritger-Peppas equation model. Cytotoxicity assays indicated minimal toxicity of the nanocarrier. Enhanced cellular uptake by MCF7 cells was observed for carriers functionalized with folate and polyethyleneimine. These findings highlight the potential of functionalized graphene oxide as a promising carrier for oridonin delivery in biomedical applications.

Investigation Cytotoxicity and Curcumin Release Behavior by Pyranopyrazole-TiO2@niosome Carrier for Breast Cancer Treatment.

In the present study, we present a pyranopyrazole-TiO2 which is encapsulated with a niosome as nanocarrier for delivery of curcumin into breast cancer cells. Nanocarrier porous TiO2 is biocompatible and with a high specific surface area and a large pore volume and was used to carry pyranopyrazole, which has been reported as an anti-cancer. Niosome in the outer layer, helpful for loading curcumin into the niosomal layer, demonstrates a pH-dependent release and can be effective for cancer treatment. Entrapment efficiency of curcumin was found at 81.02% in carriers. The results of MTT and flow cytometry revealed that apoptosis is notably enhanced by loading curcumin on pyranopyrazole-TiO2@niosome. Also, there was high biocompatibility with MCF-10A, while exhibiting significant anti-cancer and anti-metastatic effects on MCF-7, whose cell viability was 38.79% in the loaded curcumin on carrier and was more than other samples even, than free curcumin (42.82%). Furthermore, the regulation of gene expression in cancer cells decreased the regulation of MMP-2 and MMP-9 genes and increased the expression of caspase-3 and caspase-9 genes. Finally, fluorescence activity in MCF-7 significantly increased after treatment with samples.

Nitro-aniline based tripodal nitric oxide (NO) releasing molecule and light-triggered cytotoxicity in cancer cells

Trimesic acid-based novel tripodal nitric oxide (NO) donor Tris-NTA has been reported for the light-controlled NO release in organic and aqueous medium. Tris-NTA gradually releases NO in blue light (410 nm), the amount and rate of NO released can be easily modulated and controlled by merely varying the concentration of Tris-NTA and light. UV–Vis studies and Griess assay confirmed the effective steady and slow release of NO from the Tris-NTA. pH-dependent NO release studies confirm that NO release is relatively fast in at acidic medium compared to other conditions studied. Having three NO-releasing units in a single molecule, Tris-NTA was found to have a good quantum yield and fast NO release rate as compared to model compound 1 having only one NO donor. In vitro cytotoxicity tests demonstrate that the Tris-NTA is non-toxic to the cells up to the concentration of 20 μg/mL. However, Cell viability studies on human prostate cancer in the presence of light at different times suggest that the compound is toxic to the cancer cells DU145, only with light. The NO released from Tris-NTA is responsible for the cell death. Cytotoxicity result suggests that Tris-NTA could be a capable new NO donor for treating human prostate cancer.

An intelligent and self-assembled nanoscale metal organic framework (99mTC-DOX loaded Fe3O4@FeIII-tannic acid) for tumor targeted chemo/chemodynamic theranostics

BackgroundRecent advances in clinical transformation research have focused on chemodynamic theranostics as an emerging strategy for tackling cancer. Nevertheless, its effectiveness is hampered by the tumor's glutathione antioxidant effect, poor acidic tumor microenvironment (TME) and inadequate endogenous H2O2. Hence, we designed an activatable theranostics (99mTc-DOX loaded AA-Fe3O4@FeIII-TA) that effectively boost the catalytic efficiency of the Fenton-reaction-induced ROS production and augment the chemotherapeutic efficacy combined with diagnostic action.ResultsA cross-linked matrix of tannic acid-ferric salt (FeIII-TA) as a pH-responsive shell onto ascorbic acid-decorated iron-oxide nanoparticles (AA-Fe3O4NPs) was prepared demonstrating a metal–organic- framework (MOF) nanostructure, followed by loading of 99mTc-labelled DOX. The platform (99mTc-DOX loaded AA-Fe3O4@FeIII-TA) displayed suitable physical–chemical properties, including 69.8 nm particle size, 94.8 nm hydrodynamic size, − 21 mV zeta potential, effective FeIII-TA shell crosslinking onto AA-Fe3O4NPs and 94% loading efficiency for 99mTc-DOX. The results of the in-vitro release investigations showed that the platform exhibited a pH-dependent release manner with 98.3% of the 99mTc-DOX being released at pH 5 (simulating the tumor’s pH) and only 10% being released at the physiological pH (pH 7.4). This indicates that there was negligible payload leakage into the systemic circulation during the platform's passive accumulation inside tumor. Due to the acidic TME nature, the MOF shell might be degraded releasing free FeIII, TA and a sustained release of 99mTc-DOX. Besides its chemotherapeutic impact and capacity to raise intracellular H2O2 content, the released 99mTc-DOX might be used as SPECT imaging tracer for concurrent tumor diagnosis. Furthermore, the mild acidity of the tumor may be overcome by the released TA, which might raise the acidification level of cancer cells. The released FeIII, TA and the endogenous GSH could engage in a redox reaction that depletes GSH and reduces FeIII to FeII ions which subsequently catalyze the elevated concentration of H2O2 to reactive •OH via Fenton-like reaction, increasing the effectiveness of chemodynamic therapy. Moreover, the in-vivo evaluation in tumor-bearing mice showed significant radioactivity accumulation in the tumor lesion (16.8%ID/g at 1 h post-injection) with a potential target/non-target ratio of 8.ConclusionsThe 99mTc-DOX loaded AA-Fe3O4@FeIII-TA could be introduced as an effective chemo/chemodynamic theranostics.Graphical

The effect of PEGylation components on drug release behavior of targeted reduced graphene oxide based drug delivery system

Reduced graphene oxide (rGO) is a restored, defect-free version of graphene oxide (GO) with regained graphene-like properties but encounters challenges in biomedical applications due to its low solubility. Especially for drug release applications, rGO’s stronger π-π interaction of rGO compared to GO leads to low release, often demanding novel approaches for enhancement. The recently developed PEGylation method utilizes a copolymer with tunable PEG chain length and density for the PEGylation of GO simultaneously reduced to rGO, resulting in water-dispersible and biocompatible rGO-based nanoplatforms. This copolymer integrates functional monomers and enhances treatment options. Herein, we investigated how these PEGylation components and their incorporation order impact rGO’s drug release behavior. A series of copolymers, (P(PEGMA-co-AzPMA-co-MMA-co-PMA), with different PEG brushes and azide groups, were synthesized via atom transfer radical polymerization. We explored the impact of ionic azide groups on drug release by comparing the azide-containing and azide-capped copolymers. Moreover, copolymers containing 500 or 2000 Da PEG brushes were compared to assess their role as a coating layer or diffusion barrier on drug release. Doxorubicin, a hydrophobic anticancer agent, was loaded onto the rGO surface before or after peptide-based targeting agent (EPPT1) conjugation. The results showed that the drug release behavior of 500 or 2000 Da PEG brushes containing rGO surfaces are different due to the density of PEG coating which makes the effect of azide groups not always visible. Incorporating the targeting peptide before drug loading was found to be optimal. The pH-dependent release profiles revealed 49 % and 44 % release from the rGO surface for the shorter and longer PEG brushes, respectively. Tuning the PEGylation components may further influence the release behavior.

Radiation synthesis and characterization of pH-Responsive sodium Alginate/Poly(acrylic acid) nanogel loaded with ferulic acid for anticancer drug delivery

This study focuses on the synthesis and characterization of a pH-responsive nanogel system composed of sodium alginate (NaAlg) and poly(acrylic acid) loaded with ferulic acid. The mechanism of nanogel formation by gamma irradiation was elucidated, highlighting the role of polymer interactions and crosslinking agents. The pHdependent release of ferulic acid from the nanogel carrier was investigated, revealing a controlled release behavior in response to pH variations. The zeta potential values remained slightly negative across the pH range, indicating the presence of surface functional groups. Transmission electron microscopy confirmed the nanogel's formation and uniform particle size at pH 1. This nanogel was considered for controlled drug delivery applications, exhibiting high physical and chemical stability of ferulic acid. Our nanogel compound 5 decreased IC50 against HepG2, A549, MCF-7 and HCT-116 by 58.22 %, 78.35 %, 45.81 %, and 47.94 % respectively. Additionally, it decreased IC50 against VEGFR2 and EGFRT790 M by 41.94 %, and 70.59 % respectively.

Polymeric carriers of vanadyl ions based on copolymers of N-vinylpyrrolidone with vinylimines

In this study, a series of new chelating copolymers containing 20% azomethine groups, poly(N-vinylpyrrolidone-co-vinylsalicylideneimine) (poly[VP-co-VSalI]), poly(N-vinylpyrrolidone-co-vinylpicolinideneimine) (poly[VP-co-VPicI]), poly(N-vinylpyrrolidone-co-vinylpyridoxylideneimine) (poly[VP-co-VPyrI]) with M = 63000 Da and their vanadium(IV) complexes – poly(VP-co-VSalI)-VO, poly(VP-co-VPicI)-VO, poly(VP-co-VPyrI)-VO, were designed and synthesized. These are intended for the delivery and pH-dependent release of vanadium species in the intestine environment. The chelating polymers were obtained from poly(N-vinylpyrrolidone-co-N-vinylamine) (poly[VP-VAm]) by polymer-analogous transformations with the corresponding aldehydes. The vanadium content, determined by ICP-AES and spectrophotometric methods, was 5.36%, 4.99%, and 9.1% of the dry mass for poly(VP-co-VSalI)-VO, poly(VP-co-VPyrI)-VO, and poly(VP-co-VPicI)-VO, respectively. XPS data confirmed that only vanadium(IV) is presented in the complexes. All complexes demonstrated a pH-dependent release of low molecular weight vanadium species, making them promising candidates for the development of vanadium-containing systems for oral administration. These systems protect the main vanadium content in the stomach but can release biologically active ions in the intestine.

Targeted pH-responsive delivery of rosmarinic acid via phenylboronic acid functionalized mesoporous silica nanoparticles for liver and lung cancer therapy

Currently, chemotherapy is one of the most practiced approaches for the treatment of cancers. However, existing chemotherapeutic drugs have poor aqueous solubility, poor selectivity, higher systematic toxicity, and poor target accumulation. In this study, we designed and synthesized a boronic acid/ester-based pH-responsive nano-valve that specifically targets the microenvironment in cancer cells. The nano-valve comprises phenylboronic acid-coated mesoporous silica nanoparticles (B-MSN) loaded with polyphenolic compound Rosmarinic acid (ROS-B-MSN). The nano-valve was further coated with lignin (LIG) to achieve our desired LIG-ROS-BMSN nano-valve for targeted chemotherapy against Hep-G2 and NCI-H460 cell lines. The structure and properties of NPs were characterized by Fourier-transformed infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) in combination with EDX, and Dynamic light scattering (DLS). The outcomes revealed that the designed LIG-ROS-BMSN were in the nanorange (144.1 ± 0.70 nm), had negative Zeta potential (-15.7 ± 0.46 mV) and had a nearly spherical morphology. In vitro, drug release investigations showed a controlled pH-dependent release profile under mild acidic conditions that could enhance the targeted chemotherapeutic response against cancer in mild acidic environments. The obtained LIG-ROS-BMSN nano valve achieved significantly lower IC50 values of (1.70 ± 0.01 μg/mL and 3.25 ± 0.14 μg/mL) against Hep-G2 and NCI-H460 cell lines as compared to ROS alone, which was (14.0 ± 0.7 μg/mL and 29.10 ± 0.25 μg/mL), respectively. The cellular morphology before and after treatment was further confirmed via inverted microscopy. The outcomes of the current study imply that our designed LIG-ROS-BMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Preparation, characterization and evaluation of HPβCD-PTX/PHB nanoparticles for pH-responsive, cytotoxic and apoptotic properties

Paclitaxel (PTX) is a potent anticancer drug. However, PTX exhibits extremely poor solubility in aqueous solution along with severe side effects. Therefore, in this study, an inclusion complex was prepared between PTX and hydroxypropyl-β-cyclodextrin (HPβCD) by solvent evaporation to enhance the drug's solubility. The HPβCD-PTX inclusion complex was then encapsulated in poly-3-hydroxybutyrate (PHB) to fabricate drug-loaded nanoparticles (HPβCD-PTX/PHB NPs) by nanoprecipitation. The HPβCD-PTX/PHB NPs depicted a higher release of PTX at pH 5.5 thus demonstrating a pH-dependent release profile. The cytotoxic properties of HPβCD-PTX/PHB NPs were tested against MCF-7, MDA-MB-231 and SW-620 cell lines. The cytotoxic potential of HPβCD-PTX/PHB NPs was 2.59-fold improved in MCF-7 cells in comparison to free PTX. Additionally, the HPβCD-PTX/PHB NPs improved the antimitotic (1.68-fold) and apoptotic (8.45-fold) effects of PTX in MCF-7 cells in comparison to PTX alone. In summary, these pH-responsive nanoparticles could be prospective carriers for enhancing the cytotoxic properties of PTX for the treatment of breast cancer.

Fabrication of hydrophobic drug-loaded Zeolitic Imidazolate Framework-8 (ZIF-8) for enhanced anti-bacterial activity

Current study presents a novel approach for constructing small hydrophobic biomolecules embedded within zeolitic imidazolate framework-8 (ZIF-8) with exceptional antibacterial properties. In this method, ZIF-8 is synthesized from zinc acetate and 2-methylimidazole in the presence or absence of small hydrophobic bioactive molecules like rutin, rosmarinic acid, and morin. Scanning electron microscopy (SEM) analysis reveals that the synthesized ZIF-8 nanoparticles exhibit mostly hexagonal shape with size 200 nm which is further increased upon drug encapsulation. The synthesis of ZIF-8 and drug-loaded ZIF-8 is confirmed through FTIR, UV–vis spectroscopy, XRD, TGA, and EDX analyses. Zeta potential measurements show values ranging from -14.5 to -23.97 mV for both ZIF-8 and drug-loaded ZIF-8 nanoparticles. The drug loading content is determined to be 5 %, 9 %, and 16 % for morin, rutin, and rosmarinic acid, respectively. All the drug-loaded ZIF-8 formulations exhibit a pH-dependent drug release pattern, with maximal drug release observed at lower pH levels. Most importantly, these formulations demonstrate potent antibacterial activity against both Gram-positive (Enterococcus faecalis and Bacillus subtilis) and Gram-negative (Escherichia coli) bacterial strains. Specifically, ZIF-8/RUT exhibit maximum zone of inhibition (ZOI ∼ 51 mm) against all tested bacterial strains. ZIF-8/MOR and ZIF-8/RUT exhibit MIC values ranging from 2.0 to 3.0 mg/mL and MBC values from 6 to 9 mg/mL against all the tested bacteria. Among the formulations, ZIF-8/MOR and ZIF-8/RUT exhibit synergistic antibacterial effect, whereas ZIF-8/RMA possess less antibacterial potency against all the tested bacteria and mostly exhibit additive effect. Our findings suggest that these newly developed nano-formulations hold potential for the creation of highly effective antibacterial agents.

Synergistic strategies for enhanced liver cancer therapy with sorafenib/resveratrol PEGylated liposomes in vitro and in vivo

This study investigates the therapeutic efficacy of sorafenib (Sr) and resveratrol (Rv) encapsulated in liposomal formulations for liver cancer treatment. In vitro release profiles demonstrated sustained drug release, with 70 % and 56.7 % at intestinal pH of 6.8 and 79.3 % and 74.2 % at gastric pH of 1.2 after 72 h for liposomal (Sr/Rv-Lip) and PEGylated liposomal (Sr/Rv-PEG-Lip) formulations. pH-dependent release patterns highlighted adaptability of these formulations to distinct physiological conditions, crucial for targeted drug delivery. Stability assessments over three months revealed a marginal 8.5 % decrease in Sr/Rv-PEG-Lip encapsulation efficiency, accompanied by nonsignificant alterations in size, zeta potential, and polydispersity index (PDI). These indicate the formulations' capability to preserve physicochemical properties, offering promising enhanced stability for Sr and Rv. In vitro studies demonstrated superior anticancer effects of Sr/Rv-PEG-Lip with an IC50 of 5.1 μM, showing 3.1-fold increased potency, compared to Sr/Rv in H22 cells, demonstrating enhanced cytotoxicity. Sr/Rv-PEG-Lip, compared to Sr/Rv, was 50.5 and 33.1 % more potent in inhibiting proliferation and migration of H22 cells, respectively. The reactive oxygen species (ROS) assay underscored the synergistic potential of Sr and Rv, with PEGylation amplifying oxidative stress induction by 1.4-fold. In vivo, Sr/Rv-PEG-Lip demonstrated superior efficacy in suppressing tumor growth by reducing the tumor volume to 380.4 mm³ and inhibiting the weight gain by 22.7 % with minimal toxicity, demonstrating its translational potential in liver cancer therapy. These findings contribute valuable insights into nanomedicine, suggesting Sr/Rv-loaded PEGylated liposomes as a promising avenue for liver cancer treatment.

Folate functionalized multifunctional CuO@PHBV@PDA nanoplatform for pH-Responsive dual drug delivery and ROS-driven apoptosis in breast cancer

Current anticancer nanocarriers are still constrained by a disparity between their various functionalities and biocompatibility. Drug combinations delivered via cell-specific nanocarriers have the potential to improve therapeutic efficacy. Herein, we prepared a ROS-responsive CuO nanoparticle drug delivery system for treating breast cancer loaded with 5-Fluorouracil (5-FU) and paclitaxel (PTX), encased in a layer of PHBV/PDA and embellished with folate to yield 5-FU@PTX-CuO@PHBV@PDA/FA NPs. Excellent monodispersity, size stability, and biocompatibility were displayed by the resulting nanoplatform with a diameter of about 186.3 ± 7.2 nm. Synthesized nanoplatform was studied in NIH 3T3 and MCF-7 cells to determine their antitumor mechanism. Invitro pH-dependent drug release rate, drug encapsulation, loading efficiency, and hemocompatibility were all quantified via Ultraviolet–visible spectroscopy. Half-maximal inhibitory concentration values for dual drug-loaded CuO@PHBV@PDA/FA NPs and free drugs combination were 12.5 and 25 μg/mL, respectively, indicating considerably stronger antitumor activity of 5-FU@PTX-CuO@PHBV@PDA/FA NPs than free drugs combination. Apoptotic cell death, mitochondrial membrane potential loss, and ROS production were also examined in vitro. In contrary, dual drug-loaded nanoparticles exhibited concentration-dependent and synergistic cytotoxicity towards MCF-7 cells. Together, these findings suggest that the 5-FU@PTX-CuO@PHBV@PDA/FA nanoplatform may help to resolve the conflict between the multifunctionality and biocompatibility of nanocarriers.

Development and Characterization of Enteric Polymer-based Solid Dispersion for Cholecalciferol Delivery

Background: The deficiency of vitamin D is a global concern affecting individuals of all age groups. Insufficient exposure to sunlight and disease conditions can lead to cholecalciferol (vitamin D3) deficiency. Objective: Cholecalciferol is a lipophilic crystalline molecule, and it is highly susceptible to degradation under environmental conditions, including light, temperature, and oxygen, and its degradation rate is high in the low pH range. Therefore, an enteric solid dispersion-based formulation was developed in the present study for the oral delivery of cholecalciferol. Method: Enteric polymer hydroxypropylmethylcellulose acetate succinate (HPMCAS)-based solid dispersion was developed and characterized by Fourier transform-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction analysis. The effect of various concentrations of cholecalciferol formulations on the viability of Caco-2 cells was determined using an MTT assay. A dissolution and stability study of the product was also performed. Result: An amorphous form of cholecalciferol in the solid dispersion was reported. The drug content of solid dispersions was in the order of 90%. The viability assay indicated that the surfactant used in the developed solid dispersion of cholecalciferol had no cytotoxic effect on Caco-2 cells. A dissolution study on enteric solid dispersion in two-stage dissolution under a biomimetic medium indicated the pHdependent release of cholecalciferol from the HPMCAS-based solid dispersion. Moreover, the stability study showed no significant changes in the cholecalciferol content in the developed formulation under storage at experimental conditions. Conclusion: The enteric solid dispersion of cholecalciferol was developed, which exhibited compatibility with Caco-2 cells, improved dissolution, and acceptable stability profile, and represented a potential option for efficient delivery of cholecalciferol.

Synthesis of multi-responsive poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles in aqueous solution for application as glucose-sensitive insulin-releasing nanoparticles.

This study aimed to present an innovative method for synthesizing pH-thermo-glucose responsive poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles via single-step aqueous free radical polymerization. The synthesis process involved free radical polymerization in an aqueous solution, and the resulting nanoparticles were characterized for their physical and chemical properties by 1H NMR, Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). Insulin-loaded poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles were prepared and evaluated for their insulin capture and release properties at different pH and temperature, in addition to different glucose concentrations, with the release profile of insulin quantitatively evaluated using the Bradford method. 1H NMR results confirmed successful PBA incorporation, and DLS outcomes consistently indicated a transition to a more hydrophobic state above the Lower Critical Solution Temperature (LCST) of NIPA and DMAEMA. While pH responsiveness exhibited variation, insulin release generally increased with rising pH from acidic to neutral conditions, aligning with the anticipated augmentation of anionic PBA moieties and increased hydrogel hydrophilicity. Increased insulin release in the presence of glucose, particularly for formulations with the lowest mol % PBA, along with a slight increase for the highest mol % PBA formulation when increasing glucose from 1 to 4mg/mL, supported the potential of this approach for nanoparticle synthesis tailored for glucose-responsive insulin release. This work successfully demonstrates a novel method for synthesizing responsive hydrogel nanoparticles and underscores their potential for controlled insulin release in response to glucose concentrations. The observed pH-dependent insulin release patterns and the influence of PBA content on responsiveness highlight the versatility and promise of this nanoparticle synthesis approach for applications in glucose-responsive drug delivery systems. Poly(NIPA) nanoparticles containing PBA moieties are normally synthesized in two or more steps in the presence of organic solvents. Here we propose a new method for the synthesis of multiresponsive hydrogel poly(NIPA-co-DMAEMA)-PBA nanoparticles in aqueous medium in a single reaction to provide a fast and effective strategy for the production of glucose-responsive multi-systems in aqueous media from free radical polymerization.

Folate-Mediated Targeting and Controlled Release: PLGA-Encapsulated Mesoporous Silica Nanoparticles Delivering Capecitabine to Pancreatic Tumor.

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC50 value of 146.37 μg/ml and 105.90 μg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

Synergistic effect of mesoporous silica nanocarrier-assisted photodynamic therapy and anticancer agent activity on lung cancer cells

Investigating combined treatment methodologies is crucial for addressing the complex nature of cancer. As an emerging strategy, nano-biotechnology encourages the design of unique nanocarriers possessing simultaneous therapeutic application properties. This study aims to explore the combined effects of photodynamic and anticancer treatments using a multifunctional nanocarrier system co-administering the photosensitizer IR780 and the anticancer agent curcumin (Cur) on lung cancer cells. Nanocarriers were prepared by encapsulation IR780 and Cur inside polyethylene glycol-capped mesoporous silica nanoparticles (Cur&IR780@MSN). Various concentrations of nanocarriers were evaluated on A549 cells following 5 min NIR laser light (continuous wave, 785 nm, 500 mW/cm2) irradiation. The internalization of nanocarriers was observed through the fluorescence of Cur. Changes in cell viability were determined using the MTT assay and AO/PI staining. A scratch assay analysis was also performed to examine the impact of combined treatments on cell migration. Characterization of the nanocarriers revealed adequate hydrophobic drug loading, temperature-inhibited feature, enhanced reactive oxygen species generation, a pH-dependent curcumin release profile, and high biocompatibility. Cur&IR780@MSN, which enabled the observation of synergistic treatment efficacy, successfully reduced cell viability by up to 78%. In contrast, monotherapies with curcumin-loaded nanocarriers (Cur@MSN) and IR780-loaded nanocarriers (IR780@MSN) resulted in a 38% and 56% decrease in cell viability, respectively. The constructed Cur&IR780@MSN nanocarrier has demonstrated remarkable performance in the application of combination therapies for lung cancer cells. These nanocarriers have the potential to inspire future studies in tumor treatment methods.