The heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity, as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high-resolution computed tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature, which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate-stabilized or passivated with bovine serum albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and inductively coupled plasma optical emission spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n = 8 mice/group). A significant difference is highlighted between citrate-GNP and BSA-GNP groups (** p < 0.005, Tukey's multiple comparisons test), confirming that the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo, highlighting the spatial heterogeneity of the solid tumor.

The growing interest in natural bioactive molecules, as an approach to many pathological contexts, is widely justified by the necessity to overcome the disadvantageous benefit-risk ratio related to traditional therapies. Among them, mangiferin (MGF) shows promising beneficial properties such as antioxidant, anti-inflammatory, and immunomodulatory effects. In this study, we aimed to investigate the antioxidant and anti-inflammatory properties of MGF on lipopolysaccharide (LPS)-induced lung NCI-H292 cells, focusing on its role against COVID-19 adsorption. In order to obtain this information, cells treated with LPS, with or without MGF, were analyzed performing wound healing, gene expression of inflammatory cytokines, GSH quantification, and JC-1 staining. Moreover, the inhibition of viral adsorption was evaluated microbiologically and the results were further confirmed by molecular docking analysis. In this regard, MGF downregulates the expression of several inflammatory factors, enhances GSH levels, promotes the wound healing rate, and restores the mitochondrial dysfunction caused by LPS. In addition, MGF significantly inhibits SARS-CoV-2 adsorption as shown by the gene expression of ACE2 and TMPRSS-2, and furtherly confirmed by microbiological and molecular modeling evaluation. Although more investigations are still needed, all data obtained constitute a solid background, demonstrating the cytoprotective role of MGF in inflammatory mechanisms including COVID-19 infection.

For reducing side effects and improvement of swallowing, we studied the encapsulation of activated carbon formulations with a hollow-type spherical bacterial cellulose (HSBC) gel using two kinds of encapsulating methods: Methods A and B. In Method A, the BC gelatinous membrane was biosynthesized using Komagataeibacter xylinus (K. xylinus) at the interface between the silicone oil and cell suspension containing activated carbon. In Method B, the bacterial cellulose (BC) gelatinous membrane was formed at the interface between the cell suspension attached to the alginate gel containing activated carbon and the silicone oil. After the BC gelatinous membrane was biosynthesized by K. xylnus, alginate gel was removed by soaking in a phosphate buffer. The activated carbon encapsulated these methods could neither pass through the BC gelatinous membrane of the HSBC gel nor leak from the interior cavity of the HSBC gel. The adsorption ability was evaluated using indole, which is a precursor of the uremic causative agent. From curve-fitting, the adsorption process followed the pseudo-first-order and intra-particle diffusion models, and the diffusion of the indole molecules at the surface of the encapsulated activated carbon within the HSBC gel was dominant at the initial stage of adsorption. It was observed that the adsorption of the encapsulated activated carbon by the intraparticle diffusion process became dominant with longer adsorption times.

Long-acting preparations containing the antipsychotic paliperidone for intramuscular injection has drawn considerable attention to achieve harmless long-term treatment. This study aimed to develop paliperidone loaded polycaprolactone (PCL) nanoparticles and investigate the influence of PCL/drug ratio, stabilizer type, and chitosan coating on physicochemical properties, protein adsorption, and cellular toxicity. Results showed that chitosan coating produced enlarged particle sizes, shifted the surface charges from negative into positive and did not influence encapsulation efficiencies. Chitosan coating relatively sustained the drug release especially in pluronic stabilized formulations. Pluronic F127 based formulations exhibited the least protein adsorption (384.3 μg/mL). Chitosan coating of Tween 80 and polyvinyl alcohol stabilized formulations significantly (p < 0.05) increased protein adsorption. Cellular viability was concentration-dependent and negatively affected by stabilizers. All formulations did not show cellular death at 1.56 μg/mL. Inflammatory responses and oxidative stress were less affected by Tween 80 compared with other stabilizers. Chitosan minimized all aspects of cellular toxicity. Collectively, stabilizer type and chitosan coating play critical roles in developing safe and effective long-acting PCL nanoparticles intended for parenteral drug delivery. The coated formulations containing Tween 80 and Pluronic F127 as stabilizers are warranted a future in vivo study to delineate its safety and efficacy profiles.

Several approaches have evolved to facilitate the exploration of hydrogel systems in biomedical research. In this sense, poly(vinyl alcohol) (PVA) has been widely used in hydrogel (HG) fabrication for several therapeutic applications. The biological properties of PVA hydrogels (PVA-HGs) are highly dependent on their interaction with protein receptors and extracellular matrix (mainly calcium) deposition, for which there is not enough evidence from existing research yet. Thus, for the first time, the functional properties, like protein and mineral interactions, related to the proliferation of mesenchymal stem cells (MSCs) by silver nanoparticle (AgNP)-loaded PVA hydrogels (AgNPs-PVA-HGs) were investigated in the present study. The UV absorption spectrum and TEM microscopic results showed a maximum absorbance of synthesized AgNPs at 409 nm, with an average particle size of 14.5 ± 2.5 nm, respectively. The functional properties, such as the calcium-binding and the protein adsorption of PVA-HG, were accelerated by incorporating AgNPs; however, the swelling properties of the HGs were reduced by AgNPs, which might be due to the masking of the free functional groups (hydroxyl groups of PVA) by AgNPs. SEM images showed the presence of AgNPs with a more porous structure in the HGs. The proliferative effect of MSCs increased over culture time from day 1 to day 7, and the cell proliferative effect was upregulated by HGs with more pronounced AgNPs-PVA-HG. In addition, both HGs did not produce any significant cytotoxicity in the MSCs. The histological (bright light and H&E staining) and fluorescence microscopic images showed the presence of a cytoskeleton and the fibrillar structure of the MSCs, and the cells adhered more firmly to all HGs. More fibrillar bipolar and dense fibrillar structures were seen in the day 1 and day 7 cultures, respectively. Interestingly, the MSCs cultured on AgNPs-PVA-HG produced extracellular matrix deposition on day 7. Accordingly, the present results proved the biocompatibility of AgNPs-PVA-HG as a suitable system for culturing mammalian stem cells for regenerative tissue applications.

Orlistat, an anti-obesity drug, has two critical issues-the first is its low efficacy due to low water solubility and the second is side effects such as oily spotting due to its lipase inhibition. The present study was designed to propose a solution using a formulation with mesoporous silica to simultaneously overcome two issues. Orlistat was loaded onto mesoporous silica by the supercritical melt-adsorption (SCMA) method, using carbon dioxide (CO2). Various types of mesoporous silica were used as adsorbents, and the effects of the pore volume, diameter and particle size of mesoporous silica on the pharmaceutical characteristics were evaluated by various solid-state characterization methods and in vitro and in vivo studies in relation to pharmacological efficacy and the improvement of side effects. The results showed that the pore volume and diameter determine loadable drug amount inside pores and crystallinity. The dissolution was significantly influenced by crystallinity, pore diameter and particle size, and the inhibition of lipase activity was in proportion to the dissolution rate. In vivo studies revealed that the serum triglyceride (TG) concentration was significantly decreased in the group administered amorphous orlistat-loaded Neuisilin®UFL2 with the highest in vitro dissolution rate and lipase activity inhibition in comparison to the commercial product. Furthermore, oily spotting tests in rats revealed that undigested oil was adsorbed onto mesoporous silica after orlistat was released in the gastro-intestinal tract, and it correlated with in vitro result that oil adsorption capacity was dependent on the surface area of empty mesoporous silica. Therefore, it was concluded that mesoporous silica type plays a major role in determining the pharmaceutical characteristics of orlistat formulation prepared using SCMA with CO2 for improving the low solubility and overcoming the side effects.

The adsorption of biomolecules on nanoparticles' surface ultimately depends on the intermolecular forces, which dictate the mutual interaction transforming their physical, chemical, and biological characteristics. Therefore, a better understanding of the adsorption of serum proteins and their impact on nanoparticle physicochemical properties is of utmost importance for developing nanoparticle-based therapies. We investigated the interactions between potentially therapeutic proteins, neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF), and polyethylene glycol (PEG), in a cell-free system and a retinal pigmented epithelium cell line (ARPE-19). The variance in the physicochemical properties of PEGylated NT3-BDNF nanoparticles (NPs) in serum-abundant and serum-free systems was studied using transmission electron microscopy, atomic force microscopy, multi-angle dynamic, and electrophoretic light scattering. Next, we compared the cellular response of ARPE-19 cells after exposure to PEGylated NT3-BDNF NPs in either a serum-free or complex serum environment by investigating protein release and cell cytotoxicity using ultracentrifuge, fluorescence spectroscopy, and confocal microscopy. After serum exposure, the decrease in the aggregation of PEGylated NT3-BDNF NPs was accompanied by increased cell viability and BDNF/NT3 in vitro release. In contrast, in a serum-free environment, the appearance of positively charged NPs with hydrodynamic diameters up to 900 nm correlated with higher cytotoxicity and limited BDNF/NT3 release into the cell culture media. This work provides new insights into the role of protein corona when considering the PEGylated nano-bio interface with implications for cytotoxicity, NPs' distribution, and BDNF and NT3 release profiles in the in vitro setting.

Atherosclerotic disease is a substantial global burden, and existing treatments, such as statins, are recommended to lower low-density lipoprotein cholesterol (LDL-C) levels and inhibit the progression of atherosclerosis. However, side effects, including gastrointestinal unease, potential harm to the liver, and discomfort in the muscles, might be observed. In this study, we propose a novel method using periodic mesoporous silica nanoparticles (PMS) to create heparin-modified PMS (PMS-HP) with excellent biocompatibility, enabling selective removal of LDL-C from the blood. In vitro, through the introduction of PMS-HP into the plasma of mice, we observed that, compared to PMS alone, PMS-HP could selectively adsorb LDL-C while avoiding interference with valuable components such as plasma proteins and high-density lipoprotein cholesterol (HDL-C). Notably, further investigations revealed that the adsorption of LDL-C by PMS-HP could be well-fitted to quasi-first-order (R2 = 0.993) and quasi-second-order adsorption models (R2 = 0.998). Likewise, in vivo, intravenous injection of PMS-HP enabled targeted LDL-C adsorption (6.5 ± 0.73 vs. 8.6 ± 0.76 mM, p < 0.001) without affecting other plasma constituents, contributing to reducing intravascular plaque formation (3.66% ± 1.06% vs. 1.87% ± 0.79%, p < 0.05) on the aortic wall and inhibiting vascular remodeling (27.2% ± 6.55% vs. 38.3% ± 1.99%, p < 0.05). Compared to existing lipid adsorption techniques, PMS-HP exhibited superior biocompatibility and recyclability, rendering it valuable for both in vivo and in vitro applications.

Montmorillonite (MM) colloid nanoplates have high adsorption capacity due to their large size/thickness ratio, which allows them to be used as carriers for drug delivery. Upon adsorption of the mitochondrial protein cytochrome c (cytC) onto MM plates, the composite cytC-MM particles acquire anticancer properties because of the ability of cancer cells to phagocytize submicron particles (in contrast to the normal cells). In this way, exogenous cytC can be introduced into tumor cells, thereby triggering apoptosis-an irreversible cascade of biochemical reactions leading to cell death. In the present study, we investigated the physicochemical properties of cytC-MM particles as a function of the cytC concentration in the suspension, namely, the electrophoretic mobility, the mass increment of MM monoplates upon cytC adsorption, the ratio of the adsorbed to the free cytC in the bulk, the protein density on the MM's surface, the number of cytC globules adsorbed on an MM monoplate, the concentration of cytC-MM composite particles in the suspension, and the dependence of cytotoxicity on the cytC-MM particle concentration. For this purpose, we used microelectrophoresis, static and electric light scattering, and a colon cancer cell culture to test the cytotoxic effects of the cytC-MM suspensions. The results show that the cytotoxicity depends linearly on the logarithm of the particle concentration in the cytC-MM suspension reaching 97%.

In the present study, poly(l-lactic acid) (PLLA) and poly(lactide-co-glycolide) (PLGA) hybrid nanoparticles were developed for intranasal delivery of galantamine, a drug used in severe to moderate cases of Alzheimer's disease. Galantamine (GAL) was adsorbed first in hierarchical porous carbon (HPC). Formulations were characterized by FT-IR, which showed hydrogen bond formation between GAL and HPC. Furthermore, GAL became amorphous after adsorption, as confirmed by XRD and differential scanning calorimetry (DSC) studies. GAL was quantified to be 21.5% w/w by TGA study. Adsorbed GAL was nanoencapsulated in PLLA and PLGA, and prepared nanoparticles were characterized by several techniques. Their sizes varied between 182 and 394 nm, with an exception that was observed in nanoparticles that were prepared by PLLA and adsorbed GAL that was found to be 1302 nm in size. DSC thermographs showed that GAL was present in its crystalline state in nanoparticles before its adsorption to HPC, while it remained in its amorphous phase after its adsorption in the prepared nanoparticles. It was found that the polymers controlled the release of GAL both when it was encapsulated alone and when it was adsorbed on HPC. Lastly, PLGA hybrid nanoparticles were intranasally-administered in healthy, adult, male Wistar rats. Administration led to successful delivery to the hippocampus, the brain area that is primarily and severely harmed in Alzheimer's disease, just a few hours after a single dose.

Onion-type multi-lamellar liposomes (MLLs), composed of a mixture of phosphatidylcholine and Tween 80, were analyzed for their ability to encapsulate ε-Viniferin (εVin), a resveratrol dimer. Their encapsulation efficiency (EE) was measured by UV-VIS spectroscopy using three different separation methods-ultracentrifugation, size exclusion chromatography, and a more original and advantageous one, based on adsorption filtration. The adsorption filtration method consists indeed of using syringe filters to retain the molecule of interest, and not the liposomes as usually performed. The process is rapid (less than 10 min), easy to handle, and inexpensive in terms of sample amount (around 2 mg of liposomes) and equipment (one syringe filter is required). Whatever the separation method, a similar EE value was determined, validating the proposed method. A total of 80% ± 4% of εVin was found to be encapsulated leading to a 6.1% payload, roughly twice those reported for resveratrol-loaded liposomes. Finally, the release kinetics of εVin from MLLs was followed for a 77 day period, demonstrating a slow release of the polyphenol.

The aim of this study was to investigate the effects of various stabilizers on the encapsulation efficiency and release of exenatide-loaded PLGA (poly(lactic-co-glycolic acid)) microspheres prepared by the water-in-oil-in-water (W/O/W) solvent evaporation (SE) method. It was shown that the stabilizers affected exenatide stability in aqueous solutions, at water/dichloromethane interfaces, on PLGA surfaces, or during freeze-thawing and freeze-drying procedures. Sucrose predominantly reduces instability generated during freeze-thawing and freeze-drying. Phenylalanine prevents the destabilization at the water-dichloromethane (DCM) interface through decreased adsorption. Poloxamer 188 enhances stability in aqueous solutions and prevents adsorption to PLGA. Proline and lysine decrease adsorption on PLGA surfaces. Fourier transform infra-red spectroscopy (FT-IR) was used to find the molecular interaction of additives with exenatide or PLGA. Additives used in stability assessments were then added stepwise into the inner or outer water phase of the W/O/W double emulsion, and exenatide-loaded microspheres were prepared using the solvent evaporation method. The effect of each stabilizer on the encapsulation efficiency and release behavior of microspheres correlated well with the stability assessment results, except for the negative effect of poloxamer 188. Particle size analysis using laser diffractometry, scanning electron microscopy (SEM), water vapor sorption analysis, differential scanning calorimetry (DSC), and circular dichroism (CD) spectroscopy were also employed to characterize the prepared exenatide-loaded PLGA microsphere. This study demonstrated that an adequate formulation can be obtained by the study about the effect of stabilizers on peptide stability at the preformulation step. In addition, it can help to overcome various problems that can cause the destabilization of a peptide during the microsphere-manufacturing process and sustained drug release.

P-glycoprotein (P-gp) limits the oral absorption of drug substances. Potent small molecule P-gp inhibitors (e.g., zosuquidar) and nonionic surfactants (e.g., polysorbate 20) inhibit P-gp by proposedly different mechanisms. Therefore, it was hypothesised that a combination of zosuquidar and polysorbate 20 may potentiate inhibition of P-gp-mediated efflux. P-gp inhibition by zosuquidar and polysorbate 20 in combination was assessed in a calcein-AM assay and in a transcellular etoposide permeability study in MDCKII-MDR1 and Caco-2 cells. Furthermore, solutions of etoposide, zosuquidar, and polysorbate 20 were orally administered to Sprague Dawley rats. Zosuquidar elicited a high level of nonspecific adsorption to various labware, which significantly affected the outcomes of the in vitro studies. Still, at certain zosuquidar and polysorbate 20 concentrations, additive P-gp inhibition was observed in vitro. In vivo, however, oral etoposide bioavailability decreased by coadministration of both zosuquidar and polysorbate 20 when compared to coadministration of etoposide with zosuquidar alone. For future formulation development, the present study provided important and novel knowledge about nonspecific zosuquidar adsorption, as well as insights into combinational P-gp inhibition by a third-generation P-gp inhibitor and a P-gp-inhibiting nonionic surfactant.

In this study, we synthesized hollow mesoporous silica nanoparticles (HMSNs) coated with polydopamine (PDA) and a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-modified hybrid lipid membrane (denoted as HMSNs-PDA@liposome-TPGS) to load doxorubicin (DOX), which achieved the integration of chemotherapy and photothermal therapy (PTT). Dynamic light scattering (DLS), transmission electron microscopy (TEM), N2 adsorption/desorption, Fourier transform infrared spectrometry (FT-IR), and small-angle X-ray scattering (SAXS) were used to show the successful fabrication of the nanocarrier. Simultaneously, in vitro drug release experiments showed the pH/NIR-laser-triggered DOX release profiles, which could enhance the synergistic therapeutic anticancer effect. Hemolysis tests, non-specific protein adsorption tests, and in vivo pharmacokinetics studies exhibited that the HMSNs-PDA@liposome-TPGS had a prolonged blood circulation time and greater hemocompatibility compared with HMSNs-PDA. Cellular uptake experiments demonstrated that HMSNs-PDA@liposome-TPGS had a high cellular uptake efficiency. In vitro and in vivo antitumor efficiency evaluations showed that the HMSNs-PDA@liposome-TPGS + NIR group had a desirable inhibitory activity on tumor growth. In conclusion, HMSNs-PDA@liposome-TPGS successfully achieved the synergistic combination of chemotherapy and photothermal therapy, and is expected to become one of the candidates for the combination of photothermal therapy and chemotherapy antitumor strategies.

This study aimed to design a hybrid oral liposomal delivery system for selenium nanoparticles (Lip-SeNPs) to improve the bioavailability of selenium. Thiolated chitosan, a multifunctional polymer with mucoadhesive properties, was used for surface functionalization of Lip-SeNPs. Selenium nanoparticle (SeNP)-loaded liposomes were manufactured by a single step microfluidics-assisted chemical reduction and assembling process. Subsequently, chitosan-N-acetylcysteine was covalently conjugated to the preformed Lip-SeNPs. The Lip-SeNPs were characterized in terms of composition, morphology, size, zeta potential, lipid organization, loading efficiency and radical scavenging activity. A co-culture system (Caco-2:HT29-MTX) that integrates mucus secreting and enterocyte-like cell types was used as a model of the human intestinal epithelium to determine adsorption, mucus penetration, release and transport properties of Lip-SeNPs in vitro. Thiolated Lip-SeNPs were positively charged with an average size of about 250 nm. Thiolated Lip-SeNPs tightly adhered to the mucus layer without penetrating the enterocytes. This finding was consistent with ex vivo adsorption studies using freshly excised porcine small intestinal tissues. Due to the improved mucoadhesion and retention in a simulated microenvironment of the small intestine, thiolated Lip-SeNPs might be a promising tool for oral selenium delivery.

Recently, mineral healing clays have gained much attention for wound-dressing applications. Here, we selected halloysite (HAL) clay as a biocompatible, non-toxic material that is useful as a drug delivery system to enhance the healing properties of water-soluble terpenoids 1-3 (T1-3). Terpenoids-loaded HAL clay (TH1-3) was prepared and characterized by adsorption equilibrium studies, X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and release studies. The results reveal that T1-3 were adsorbed at the HAL surface with good efficiency. The prevalent mechanism of drug retention is due to the adsorption via electrostatic interactions between the cationic groups of the T1-3 and the HAL's external surface. Release studies demonstrated that T3 was released in a higher percentage (>60%) compared to T1-2 (≈50%). Additionally, TH1-3 were assessed for their antimicrobial activity and capability to promote the re-epithelialization of scratched HaCat monolayers, through the time-kill test and the wound-healing assays, respectively. The results reveal that all the tested formulations were able to reduce the microbial growth after 1 h of incubation and that they ensured complete wound closure after 48 h. Furthermore, at the concentration of 1 µg/mL, TH3 exhibited 45% wound closure at 24 h, compared to TH1 (27%) and TH2 (30%), proving to be the best candidate in making the tissue-repair process easier and faster.

Sulfathiazole is an antimicrobial belonging to the family of sulfonamides, which were the first antibiotics to be discovered. Sulfathiazole is generally administered orally, and its main disadvantage is that it has low aqueous solubility, requiring high doses for its administration. This fact has led to side effects and the generation of bacterial resistance to the drug over time. The improvement of its solubility would mean not having to administer such high doses in its treatment. At the same time, montmorillonite is a natural, low-cost, non-toxic, biocompatible clay with a high adsorption capacity. It is potentially useful as a nanocarrier to design sulfathiazole dosage forms. In this work, the interaction between the drug and the clay mineral has been studied from an experimental and computational atomistic point of view to improve the drug's biopharmaceutical profile. The results showed the potential enhancement of the drug solubility due to the correct adsorption of the sulfathiazole in the clay interlayer space. As a result of the inclusion of sulfathiazole in the interlayer of the clay mineral, the solubility of the drug increased by 220% concerning the pristine drug. Experimentally, it was not possible to know the number of drug molecules adsorbed in the interlayer space or the external surface of the carrier. Theoretical studies will enable the knowledge of the stoichiometry of the drug/clay hybrids, with three molecules in the interlayer space being the most favorable process. The resultant basal spacing was in agreement with the experimental results.

Indocyanine green (ICG) is a safe dye widely used in the biomedical field. Its photodynamic effect (PDT), originating from laser irradiation at 803 nm, opens interesting perspectives in theranostic applications. To overcome its low water stability, ICG can be shielded with nanoparticles (NPs). In this work, previously developed NPs based on poly lactic-co-glycolic acid (PLGA) coated with chitosan oleate (CS-OA) and loaded with resveratrol as a hydrophobic model drug have been proposed as an ICG carrier. These systems have been selected for their observed immunostimulatory properties. The possible loading of the dye by adsorption onto NP surface by electrostatic interaction was studied here in comparison with the encapsulation into the PLGA core. The ICG-chitosan (CS) interaction has been characterized by spectrophotometry, spectroscopy and in-cell in vitro assays. Fluorescence quenching was observed due to the ionic interaction between ICG and CS and was studied considering the dye:polymer stoichiometry and the effect of the NP dilution in cell culture medium (DMEM). The NP systems have been compared in vitro, assessing their behaviour in Caco-2 cell lines. A reduction in cell viability was observed after irradiation of ICG associated with NPs, evident also for the samples loaded by adsorption. These findings open the opportunity to exploit the association of PDT's effect on ICG with the properties of CS-OA coated NPs, whose immunostimulatory effect can be associated with PDT mechanism in cancer therapy.

The effectiveness of oral drug administration is related to the solubility of a drug in the gastrointestinal tract and its ability to penetrate the biological membranes. As most new drugs are poorly soluble in water, there is a need to develop novel drug carriers that improve the dissolution rate and increase bioavailability. The aim of this study was to analyze the modification of sulindac release profiles in various pH levels with two APTES ((3-aminopropyl)triethoxysilane)-modified SBA-15 (Santa Barbara Amorphous-15) silicas differing in 3-aminopropyl group content. Furthermore, we investigated the cytotoxicity of the analyzed molecules. The materials were characterized by differential scanning calorimetry, powder X-ray diffraction, scanning and transmission electron microscopy, proton nuclear magnetic resonance and Fourier transformed infrared spectroscopy. Sulindac loaded on the SBA-15 was released in the hydrochloric acidic medium (pH 1.2) and phosphate buffers (pH 5.8, 6.8, and 7.4). The cytotoxicity studies were performed on Caco-2 cell line. The APTES-modified SBA-15 with a lower adsorption capacity towards sulindac released the drug in a less favorable manner. However, both analyzed materials improved the dissolution rate in acidic pH, as compared to crystalline sulindac. Moreover, the SBA-15, both before and after drug adsorption, exhibited insignificant cytotoxicity towards Caco-2 cells. The presented study evidenced that SBA-15 could serve as a non-toxic drug delivery system that enhances the dissolution rate of sulindac and improves its bioavailability.

Genistein (Gen), a kind of natural isoflavone drug monomer with poor water solubility and low oral absorption, was incorporated into oral nanoparticles with a new mesoporous carrier material, NH2-MCM-41, which was synthesized by copolycondensation. When the ratio of Gen to NH2-MCM-41 was 1:0.5, the maximum adsorption capacity of Gen was 13.15%, the maximum drug loading was 12.65%, and the particle size of the whole core-shell structure was in the range of 370 nm-390 nm. The particles were characterized by a Malvern particle size scanning machine, XRD, Fourier transform infrared spectroscopy, scanning electron microscopy, and nitrogen adsorption and desorption. Finally, Gen-NH2-MCM-41 was encapsulated by sodium alginate (SA), and the chimerism of this material, denoted as GEN-NH2-MCM-41@SA, was investigated. In vitro release experiments showed that, after 5 h in artificial colon fluid (pH = 8.0), the cumulative release reached 99.56%. In addition, its anti-rotavirus (RV) effect showed that the maximum inhibition rate was 62.24% at a concentration of 30 μM in RV-infected Caco-2 cells, and it significantly reduced the diarrhea rate and diarrhea index in an RV-infected-neonatal mice model at a dose of 0.3 mg/g, which was better than the results of Gen. Ultimately, Gen-NH2-MCM-41@SA was successfully prepared, which solves the problems of low solubility and poor absorption and provides an experimental basis for the application of Gen in the clinical treatment of RV infection.