Properties Of Nanocarriers Research Articles

Stimuli-responsive gelatin-coated alginate nanocarriers: Targeted delivery of efflux pump inhibitor and antibacterial agents to control multidrug resistant P. aeruginosa

Multidrug resistance is an inescapable obstacle in healthcare settings. As the over-expression of efflux pumps is an important mediator of bacterial drug resistance, stimuli-responsive co-delivery nanosystems were developed for the sequential release of efflux pump inhibitors (EPI) and antibacterial agents. Gelatin-coated alginate nanocarriers (AlNCs@Gel) were developed containing ciprofloxacin (Cip) and quercetin (Que) as antibacterial/antibiofilm agents and EPI, respectively. Heat plot maps revealed a synergistic interaction of Cip with Que as the minimum inhibitory concentration value of Cip was reduced in the presence of EPI (quercetin) against P. aeruginosa. The encapsulation efficiency of 82 ± 1 % was observed for Cip while it was 70 ± 1 % for Que in Cip/AlNCs@Que/Gel nanocarriers. FTIR analyses confirmed an interaction between alginate and gelatin by the occurrence of a blue shift that is associated with electrostatic interactions between alginate and gelatin. These nanocarriers loaded with quercetin as EPI would release it preferentially in the presence of gelatinase enzyme and subsequently prevent the efflux of ciprofloxacin from bacterial cells. Membrane-permeability assay confirmed no permeabilization while viability studies exhibited superior bacterial inhibition, as Cip/EPI combination encapsulated in AlNCs@Gel effectively controlled the growth of P. aeruginosa as compared to antibiotic alone in AlNCs@Gel and free drug combinations. In vitro, cytotoxicity-analysis confirmed the biocompatibility of the developed core-shell nanocarriers. Furthermore, gelatin coating improved the physico-chemical properties of nanocarriers and the on-demand-release of EPI and antibiotic molecules. Thus, smartly designed AlNCs@Gel nanocarriers for the co-delivery of EPI and antibiotics present an innovative solution for preventing drug efflux from P. aeruginosa to control resistant infections.

Modulating Elasticity of Liposome for Enhanced Cancer Immunotherapy.

Cancer immunotherapy has emerged as a promising approach to cancer treatment in recent years. The physical and chemical properties of nanocarriers are critical factors that regulate the immune activation of antigen-presenting cells (APCs) in the tumor microenvironment (TME). Herein, we extensively investigated the behavior of liposome nanoparticles (Lipo-NPs) with different elasticities, focusing on their interaction with immune cells and their transport mechanisms from tumors to tumor-draining lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct elastic properties, their varied behaviors were observed, concerning immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell membranes, while those with medium elasticity facilitated the cargo delivery to macrophages through membrane fusion. Conversely, hard Lipo-NPs enter macrophages via classical cellular uptake pathways. Additionally, it was noted that softer Lipo-NPs displayed superior transport to tdLNs in vivo, attributed to their deformable nature with lower elasticity. As a result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating the STING pathway and enhancing transport to tdLNs, promoted abundant infiltration of tumor-infiltrating lymphocytes (TILs), leading to notable antitumor effects and extended survival in a melanoma mouse model. Furthermore, this study highlighted the potential synergistic effect of medium elasticity Lipo-NPs with immune checkpoint blockade (ICB) therapy in preventing tumor immune evasion. These findings hold promise for guiding immune-targeted delivery systems in cancer immunotherapy, particularly in vaccine design for tdLNs targeting and eradicating metastasis within tdLNs.

The elasticity of silicone-stabilized liposomes has no impact on their in vivo behavior

BackgroundThe elastomechanical properties of nanocarriers have recently been discussed as important for the efficient delivery of various therapeutics. Some data indicate that optimal nanocarriers’ elasticity can modulate in vivo nanocarrier stability, interaction with phagocytes, and uptake by target cells. Here, we presented a study to extensively analyze the in vivo behavior of LIP-SS liposomes that were modified by forming the silicone network within the lipid bilayers to improve their elastomechanical properties. We verified liposome pharmacokinetic profiles and biodistribution, including retention in tumors on a mouse model of breast cancer, while biocompatibility was analyzed on healthy mice.ResultsWe showed that fluorescently labeled LIP-SS and control LIP-CAT liposomes had similar pharmacokinetic profiles, biodistribution, and retention in tumors, indicating that modified elasticity did not improve nanocarrier in vivo performance. Interestingly, biocompatibility studies revealed no changes in blood morphology, liver, spleen, and kidney function but indicated prolonged activation of immune response manifesting in increased concentration of proinflammatory cytokines in sera of animals exposed to all tested liposomes.ConclusionIncorporating the silicone layer into the liposome structure did not change nanocarriers’ characteristics in vivo. Further modification of the LIP-SS surface, including decoration with hydrophilic stealth polymers, should be performed to improve their pharmacokinetics and retention in tumors significantly. Activation of the immune response by LIP-SS and LIP-CAT, resulting in elevated inflammatory cytokine production, requires detailed studies to elucidate its mechanism.Graphical

Recombinant human epidermal growth factor-loaded liposomes and transferosomes for dermal delivery: Development, characterization, and cytotoxicity evaluation.

Recombinant human epidermal growth factor (rhEGF) is widely utilized as an antiaging compound in wound-healing therapies and cosmetic purposes. However, topical administration of rhEGF has limited treatment outcomes because of its poor percutaneous penetration and rapid proteinase degradation. To overcome these obstacles, this study aims to develop and characterize rhEGF-containing conventional liposomes (rhEGF-CLs) and transferosomes (rhEGF-TFs) as efficient dermal carriers. Physicochemical characterization such as particle size, zeta potential (ZP), morphology, encapsulation efficiency (EE%), and release properties of nanocarriers as well as in vitro cytotoxicity in human dermal fibroblast (HDF) and human embryonic kidney (HEK293) cell lines were investigated. rhEGF-TFs at the rhEGF concentration ranging from 0.05 to 1.0 μg/mL were chosen as the optimum formulation due to the desired release profile, acceptable EE%, optimal cell proliferation, and minimal cytotoxicity compared to the control and free rhEGF. However, higher concentrations caused a decrease in cell viability. The ratio 20:80 of Tween 80 to lipid was optimal for rhEGF-TFs-2, which had an average diameter of 233.23 ± 2.64 nm, polydispersity index of 0.33 ± 0.05, ZP of -15.46 ± 0.29 mV, and EE% of 60.50 ± 1.91. The formulations remained stable at 5°C for at least 1 month. TEM and SEM microscopy revealed that rhEGF-TFs-2 had a regular shape and unilamellar structure. In vitro drug release studies confirmed the superiority of rhEGF-TFs-2 in terms of optimal cumulative release of rhEGF approximately 82% within 24 h. Franz diffusion cell study showed higher rhEGF-TFs-2 skin permeation compared to free rhEGF solution. Taken together, we concluded that rhEGF-TFs can be used as a promising formulation for wound healing and skin regeneration products.

Suborgan Level Quantitation of Proteins in Tissues Delivered by Polymeric Nanocarriers.

Amidst the rapid growth of protein therapeutics as a drug class, there is an increased focus on designing systems to effectively deliver proteins to target organs. Quantitative monitoring of protein distributions in tissues is essential for optimal development of delivery systems; however, existing strategies can have limited accuracy, making it difficult to assess suborgan dosing. Here, we describe a quantitative imaging approach that utilizes metal-coded mass tags and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify the suborgan distributions of proteins in tissues that have been delivered by polymeric nanocarriers. Using this approach, we measure nanomole per gram levels of proteins as delivered by guanidinium-functionalized poly(oxanorborneneimide) (PONI) polymers to various tissues, including the alveolar region of the lung. Due to the multiplexing capability of the LA-ICP-MS imaging, we are also able to simultaneously quantify protein and polymer distributions, obtaining valuable information about the relative excretion pathways of the protein cargo and carrier. This imaging approach will facilitate quantitative correlations between nanocarrier properties and protein cargo biodistributions.

Formulating biomolecular crowns on micelles: A potential strategy for improving micelle stability

The complex environment in blood circulation has a tremendous destabilizing effect on the micelles structure, which is a vital issue to be addressed in micelles design and application. Biomolecule crowns, quickly formed on the surface of nanocarriers in vivo, may alter the physicochemical properties of nanocarriers. In this study, bovine serum albumin (BSA) or fetal bovine serum (FBS) was formulated as the biomolecular crown of the bacterial lipase-responsive micelles encapsulating the hydrophobic antibiotics chloramphenicol (CHL) to investigate their stabilization effect on the micelles. Compared with BSA-crowned micelles (BSA/PM@CHL), FBS-crowned micelles (FBS/PM@CHL) reduced drug leakage by more than 90 % without masking their lipase responsiveness, it also inhibited 77 % of bacterial growth in in vitro antibacterial activity study and significantly increased the area under plasma concentration curve and in vivo half-life in pharmacokinetic study. Then the Förster resonance energy transfer (Fret) Effect was used to further explore the mechanisms responsible for the differences between the BSA-crown and FBS-crown. The in vitro anti-dilution tests below the critical micellar concentration showed that FBS-crown could improve the thermodynamic stability of the micelles, the micelle integrity of FBS/PM was 2 times higher than that of PM diluted with aqueous dilution and 6.5 times higher than that diluted with rat plasma dilution. In vivo optical imaging study showed that micelles with dual-labeled FBS/PM (mean value = 0.363) maintained better structural integrity than dual-labeled PM (mean value = 0.325) after 4 h of injection, explaining the ability of FBS-crowned micelles to improve pharmacokinetic parameters in terms of thermodynamic stability. Besides, the destruction of PM integrity slowed down after injection into the blood circulation for 4–8h, indicating that the baring of biomolecular-crown may be in the late cycle. Overall, the biomolecular-crowned micelles strategy presents a promising strategy for maintaining the structural and functional stability of micelles under physiological conditions.

Functional surface modifications impact on the in vitro/in vivo toxicity and intracellular internalization behavior of mesoporous silica nanoparticles

The surface properties of nanocarriers, including morphology, charge and surface modification are closely associated with their in vivo toxicity, biodistribution and bioavailability, which further affect the therapeutic effect. Herein, a series of in vitro and in vivo studies, including hemolysis, protein adsorption, cytotoxicity, cellular uptake and in vivo acute toxicity were performed to investigate the influences of surface properties on the biocompatibility and intracellular internalization behavior of functionalized degradable dendritic mesoporous silica nanoparticles (DDMSNs). The results illustrated that hyaluronic acid-modified DDMSNs (DDMSNs-NH2-HA) nanocarriers showed lower hemolysis, non-specific protein adsorption and in vitro cytotoxicity compared to DDMSNs and aminated DDMSNs (DDMSNs-NH2). The HA-mediated efficient intracellular internalization and significant accumulation of DDMSNs-NH2-HA in A549 cells was observed by cellular uptake assays. Furthermore, compared to DDMSNs and DDMSNs-NH2 groups, no significant pathological abnormalities were found in the hematoxylin and eosin-stained sections of key organs induced by DDMSNs-NH2-HA nanocarriers for in vivo toxicity, indicating that the improvement of nanocarriers’ biocompatibility arose from HA modification. This work explored the influencing mechanism of surface properties on biological toxicity and intracellular internalization behavior of nanocarriers in vitro and in vivo, which provided an insight into the design of biocompatible nano-DDS by rational surface modifications.

Natural-Origin Betaine Surfactants as Promising Components for the Stabilization of Lipid Carriers.

In the present work, we demonstrate studies involving the influence of the formulation composition on the physicochemical properties of nanocarriers: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Novel lipid-origin platforms were prepared using two "green" betaine-based surfactants, cocamidopropyl betaine (ROKAmina K30) and coco betaine (ROKAmina K30B), in combination with three different solid lipids, cetyl palmitate (CRODAMOL CP), trimyristin (Dynasan 114), and tristearin (Dynasan 118). Extensive optimization studies included the selection of the most appropriate lipid and surfactant concentration for effective SLN and NLC stabilization. The control parameters involving the hydrodynamic diameters of the obtained nanocarriers along with the size distribution (polydispersity index) were determined by dynamic light scattering (DLS), while shape and morphology were evaluated by atomic force microscopy (AFM) and transmission electron microscopy (TEM). Electrophoretic light scattering (ELS) and turbidimetric method (backscattering profiles) were used to assess colloidal stability. The studied results revealed that both betaine-stabilized SLN and NLC formulations containing CRODAMOL CP as lipid matrix are the most monodisperse and colloidally stable regardless of the other components and their concentrations used, indicating them as the most promising candidates for drug delivery nanosystems with a diverse range of potential uses.

Nanocarrier drug delivery system: promising platform for targeted depression therapy.

Depression is a chronic mental disorder characterized by persistent low mood and loss of interest. Treatments for depression are varied but may not be sufficient cure. Drug-based treatment regimens have drawbacks such as slow onset of action, low bioavailability, and drug side effects. Nanocarrier Drug Delivery Systems (NDDS) has received increasing attention for brain drug delivery since it assists the drug through the blood-brain barrier and improves bioavailability, which may be beneficial for treating depression. Due to the particle size and physicochemical properties of nanocarriers, it presents a promise to improve the stability and solubility of antidepressants, thereby enhancing the drug concentration. Moreover, ligand-modified nanocarriers can be taken as a target direct medicines release system and reduce drug side effects. The purpose of the present review is to provide an up-to-date understanding of the Nanocarrier drug delivery system and relevant antidepressants in different routes of ingestion, to lay a foundation for the treatment of patients with depression.

Influence of drug molecular weight on self-assembly and intestinal permeation of polymer-based nanocarriers

For oral delivery, the physicochemical properties of nanocarriers are decisive factors for permeation through the intestinal epithelium. These properties are determined by the composition of the nanocarriers as well as by the process parameters during their self-assembly. For macromolecular drugs, there is still little understanding of the drug-polymer interactions during nanocarrier self-assembly and the effects on carrier properties. In this study, the effect of drug molecular weight on nanocarrier self-assembly, physicochemical properties of nanocarriers as well as their permeation across the intestinal epithelium was investigated. Our results show that the drug molecular weight impacts the physicochemical properties of nanocarriers. Further, the physicochemical properties of the nanocarriers, governed by the molecular weight of the drug, determine their permeation properties across the intestinal epithelium. Comparative in vitro and ex vivo studies revealed that intestinal absorption is dependent on both, the properties of the tissue as well as properties of the carrier system. In conclusion, the molecular weight of drug payload is a key factor determining the physiochemical properties of polymeric nanocarriers and is closely linked to their oral absorption. Using different preclinical models to evaluate intestinal permeation of nanocarriers allows for novel insights into key formulation properties governing oral bioavailability.

Exploring the potential of transethosomes in therapeutic delivery: A comprehensive review

AbstractThe growing need for innovative drug delivery systems has led to extensive research to address the limitations associated with conventional dosage forms. Lipid nanoparticles have become prominent as frontline nanocarriers for the delivery of drugs and vaccine formulations. However, the pursuit of new materials and modifications to improve lipid nanocarrier properties remains ongoing. In this context, transethosomes have gained attention as a promising solution, offering distinct advantages over traditional formulations. Transethosomes minimize plasma fluctuations, first‐pass metabolism, organ toxicity, and poor bioavailability. This comprehensive review provides an in‐depth exploration of transethosomes, starting with an overview of the impact of formulation components on their properties and effective targeting. This article delves into the production techniques and evaluation properties employed to ensure efficient drug delivery. A significant contribution of this review lies in the analysis of various routes of administration for transethosomes, including transdermal, transvaginal, pulmonary, and ocular delivery, showcasing the versatility of transethosome‐loaded with drugs and their potential to target specific tissues to achieve controlled release. Furthermore, the potential of functionalization and photodynamic therapy approaches to enhance drug delivery efficacy are explored. Overall, this review emphasizes the significant potentiality of transethosomes as a promising drug delivery system addressing the challenges associated with conventional drug delivery approaches.

Unsteady nano-magnetic drug dispersion for pulsatile Darcy flow through microvessel with drug elimination phenomena

Drug delivery by nano-drug carriers in magnetic drug targeting has shown a promising future in various cancer tumor treatments. The distinguishing properties of nanocarriers, such as small size, selective targeting, controlled release, and others, have made them more effective than the existing conventional treatments. However, several factors affect its delivery. In the present problem, we study the unsteady dispersion of drug-loaded magnetic nanocarriers in microvessels driven by a pulsatile pressure gradient derived from the unsteady Darcy law. Both fluid flow rate and mean velocity are computed analytically. The finite difference method is used to obtain the numerical solution of the solute transport equation, and the results are presented in graphs. Our results show that not only does the Womersley number influence the pulsatility dispersion of nanocarrier particles but also the microvessel permeability, magnetic-tumor distance, magnetization number, and volume fraction of magnetic nanoparticles. We found a drop in drug-loaded magnetic nanocarriers' concentration at the targeted site with decreasing blood pulsatility in the microvessel as portrayed by the Womersley parameter. In contrast, the descending magnetic tumor distance promotes nanoparticle concentration in the tumor tissue. Furthermore, the effects of other parameters, such as permeability, magnetization, volume fraction of magnetic nanoparticles, source term, elimination parameter, and nanocarrier radius, are discussed. To sum up, based on the Womersley frequency parameter coefficient used to describe blood pulsatility resulting from forceful heartbeat, flow pulsatility and nanocarrier particle dispersion are positively correlated, while magnetic-tumor distance is negatively correlated with both pulsatility and nanoparticle concentration.

Mathematical modelling of microneedle-mediated transdermal delivery of drug nanocarriers into skin tissue and circulatory system

Microneedle-mediated transdermal delivery using nanocarriers can successfully overcome the barrier of the stratum corneum and protect drugs from elimination in skin tissues. However, the effectiveness of drug delivery to different layers of skin tissues and the circulatory system varies considerably, subject to the properties of the drug delivery system and delivery regime. How to maximise delivery outcomes remains unclear. In this study, mathematical modelling is employed to investigate this transdermal delivery under various conditions, using the skin model that is reconstructed based on the realistic skin anatomical structure. Treatment efficacy is evaluated in terms of drug exposure over time. The modelling results demonstrate the complex dependence of drug accumulation and distribution on the nanocarrier properties, microneedle properties and environment in different skin layers and blood. Specifically, delivery outcomes in the entire skin and blood can be improved by increasing the loading dose and reducing microneedle spacing. However, several parameters need to be optimised with respect to the specific location of the target site in the tissue for better treatment; these include the drug release rate, nanocarrier diffusivity in microneedle and skin tissue, nanocarrier transvascular permeability, nanocarrier partition coefficient between tissue and microneedle, microneedle length, wind speed and relative humidity. The delivery is less sensitive to the diffusivity and physical degradation rate of free drugs in microneedle, and their partition coefficient between tissue and microneedle. Results obtained from this study can be used to improve the design of the microneedle-nanocarrier combined drug delivery system and delivery regime.

Effect of CeO2/spherical silica and halloysite nanotubes engineered for targeted drug delivery system to treat breast cancer cells

Cerium oxide nanoparticles (CeO2 NPs) and flavonoid curcumin that has been widely studied for treating diseases involving high reactive oxygen species (ROS). In nanotherapeutics, the particle size, shape, metal oxide dispersity and surface properties of nanocarriers are vital for drug delivery and therapeutic efficiency. Here, cisplatin release behavior on cerium impregnated two different shaped nanocarriers, CeO2/monodispersed spherical silica (Sil) and CeO2/halloysite (Hal) nanotube was studied for potential anti-cancer therapies. For comparison, CeO2 impregnated mesoporous silica MCM-41, SBA-16, Hydroxyapatite and clay were prepared. Subsequently, the nanocomposites were coated with curcumin (25% wt/wt), and cisplatin (Cp) functionalization (5% wt/wt). 5wt%CeO2/Hal/Cp and 5wt%CeO2/Sil/Cp samples were pegylated using lyophilization technique. Physico-chemical analyses revealed the nanosized distribution of CeO2 and functionalization of cisplatin and curcumin. Cp release was studied using automated Franz cell and dialysis membrane techniques. The different structured nanocarriers delivering mechanism was studied by determining the drug kinetic release using four different kinetic models (first order, second order, Higuchi and Korsmeyer-Peppas). In vitro cytotoxicity assay of nano formulations along with free cisplatin and curcumin (Cur) were tested against the breast cancer cell line (MCF-7) for multiple timepoints by MTT assay. The results reveled the efficacy of 5wt%CeO2/Sil/Cp/Cur nanoparticles in delivering cisplatin. On the other hand, 5wt%CeO2/Hal/Cur nanoparticles enhanced the uptake of curcumin in comparison to free curcumin. Overall, pegylated CeO2/Silica nano formulation demonstrated an effective carrier to cisplatin for potential treatment of breast cancer.

Charge, Aspect Ratio, and Plant Species Affect Uptake Efficiency and Translocation of Polymeric Agrochemical Nanocarriers.

An incomplete understanding of how agrochemical nanocarrier properties affect their uptake and translocation in plants limits their application for promoting sustainable agriculture. Herein, we investigated how the nanocarrier aspect ratio and charge affect uptake and translocation in monocot wheat (Triticum aestivum) and dicot tomato (Solanum lycopersicum) after foliar application. Leaf uptake and distribution to plant organs were quantified for polymer nanocarriers with the same diameter (∼10 nm) but different aspect ratios (low (L), medium (M), and high (H), 10-300 nm long) and charges (-50 to +15 mV). In tomato, anionic nanocarrier translocation (20.7 ± 6.7 wt %) was higher than for cationic nanocarriers (13.3 ± 4.1 wt %). In wheat, only anionic nanocarriers were transported (8.7 ± 3.8 wt %). Both low and high aspect ratio polymers translocated in tomato, but the longest nanocarrier did not translocate in wheat, suggesting a phloem transport size cutoff. Differences in translocation correlated with leaf uptake and interactions with mesophyll cells. The positive charge decreases nanocarrier penetration through the leaf epidermis and promotes uptake into mesophyll cells, decreasing apoplastic transport and phloem loading. These results suggest design parameters to provide agrochemical nanocarriers with rapid and complete leaf uptake and an ability to target agrochemicals to specific plant organs, with the potential to lower agrochemical use and the associated environmental impacts.

Bioaffinity Recovery of Linear CRGDS Peptides Grafted to Zwitterionic PAMAM Nanocarriers

Functional oligopeptides derived from natural proteins are often used as targeting groups or therapeutic drugs but always suffer from a dramatic bioaffinity decrease due to the loss of conformational restriction in proteins, which increases their entropy state. It is worth noting that the linear Cys-Arg-Gly-Asp-Ser (CRGDS) oligopeptide can spontaneously restore its natural conformation by anchoring one terminus and forming hydrogen bonds on another terminus, on protein-like zwitterionic fifth-generation polyamide-amine (G5 PAMAM) nanocarriers, thus exhibiting high bioaffinity. However, the different physicochemical properties of nanocarriers have an impact on the bioaffinity recovery of linear CRGDS. In this work, it is found that the bioaffinity decreases with the reduction of generation of PAMAM and zwitterionic G3 PAMAM is a turning point for bioaffinity recovery via a series of in vitro experiments. This indicates that the spontaneous restoration of the native conformation of the RGD segment requires proper surface group density and structural rigidity of the zwitterionic nanocarrier for reducing the entropic energy of CRGDS peptides before binding. This approach paves a way for functional reproduction of protein molecules using low-cost synthetic polymers for extensive biomedical applications.

Development of Folate‐Superparamagnetic Nanoconjugates for Inhibition of Cancer Cell Proliferation

AbstractHere, a versatile strategy to engineer smart theranostic nanocarriers is reported. The core/shell nanosystem is composed of a superparamagnetic iron oxide (Fe3−δO4) nanoparticle (NP) core bearing the biocompatible thermo‐responsive poly(2‐(2‐methoxy)ethyl methacrylate‐oligo(ethylene glycol methacrylate), P(MEO2MAx‐OEGMA100−x) copolymer (where x and 100‐x represent the molar fractions of MEO2MA and OEGMA, respectively). Folic acid (FA) is end‐conjugated to the P(MEO2MAx‐OEGMA100−x) copolymer, leading to Fe3−δO4@P(MEO2MAx‐OEGMA100−x)‐FA, to facilitate active targeting of NPs to cancer cells. A highly potent hydrophobic anticancer agent doxorubicin (DOX) is incorporated in the thermo‐responsive P(MEO2MAx‐OEGMAy) brushes via supramolecular interactions to increase its solubility and the assessment of therapeutic potentials. These experiments confirm the magnetic hyperthermia properties of nanocarrier and reveal that only a small amount (10% ± 4%) of DOX is diffused at room temperature, while almost full drug (100%) is released after 52 h at 41 °C. Interestingly, it is found that P(MEO2MA60‐OEGMA40) polymers offer to NPs a promising stealth behavior against Human Serum Albumin and Fibrinogen model proteins.

Some Nanocarrier’s Properties and Chemical Interaction Mechanisms with Flavones

Flavones such as 7,8-dihydroxyflavone (tropoflavin), 5,6,7-trihydroxyflavone (baicalein), 3',4',5,6-tetrahydroxyflavone (luteolin), 3,3',4',5,5',7-hexahydroxyflavone (myricetin), 4',5,7-trihydroxyflavone (apigenin), and 5,7-dihydroxyflavone (chrysin) are important both for their presence in natural products and for their pharmacological applications. However, due to their chemical characteristics and their metabolic processes, they have low solubility and low bioavailability. Knowledge about the physicochemical properties of nanocarriers and the possible mechanisms of covalent and non-covalent interaction between nanoparticles (NPs) and drugs is essential for the design of nanocarriers to improve the bioavailability of molecules with pharmacological potential, such as tropoflavin, baicalein, luteolin, myricetin, apigenin, and chrysin. The parameters of characterization of some NPs of these flavones, such as size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and % release/time, utilized in biomedical applications and the covalent and non-covalent interactions existing between the polymeric NPs and the drug were analyzed. Similarly, the presence of functional groups in the functionalized carbon nanotubes (CNTs), as well as the effect of pH on the % adsorption of flavonoids on functionalized multi-walled carbon nanotubes (MWCNT-COOH), were analyzed. Non-covalent interaction mechanisms between polymeric NPs and flavones, and covalent interaction mechanisms that could exist between the NPs and the amino and hydroxyl functional groups, are proposed.

Investigation of the interaction between the functionalized mesoporous silica nanocarriers and bovine serum albumin via multi-spectroscopy

It is well known that the physicochemical properties of nanocarriers, which are closely related to the surface modification of nanoparticles, have crucial impacts on their biological effects. Herein, the interaction between functionalized degradable dendritic mesoporous silica nanoparticles (DDMSNs) and bovine serum albumin (BSA) was investigated for probing into the nanocarriers’ potential toxicity using multi-spectroscopy such as ultraviolet/visible (UV/Vis), synchronous fluorescence, Raman and circular dichroism (CD) spectroscopy. BSA, owing to its structural homology and high sequence similarity with HSA, was employed as the model protein to study the interactions with DDMSNs, amino-modified DDMSNs (DDMSNs-NH2) and hyaluronic acid (HA) coated nanoparticles (DDMSNs-NH2-HA). It was found that the static quenching behavior of DDMSNs-NH2-HA to BSA was accompanied by an endothermic and hydrophobic force-driven thermodynamic process, which was confirmed by fluorescence quenching spectroscopic studies and thermodynamic analysis. Furthermore, the conformational variations of BSA upon interaction with nanocarriers were observed by combination of UV/Vis, synchronous fluorescence, Raman and CD spectroscopy. The microstructure of amino residues in BSA changed due to the existence of nanoparticles, for example, the amino residues and hydrophobic groups exposed to microenvironment and the alpha helix (α-helix) content of BSA decreased. Specially, through thermodynamic analysis, the diverse binding modes and driving forces between nanoparticles and BSA were discovered because of different surface modifications on DDMSNs, DDMSNs-NH2 and DDMSNs-NH2-HA. We believe that this work can promote the interpretation of mutual impact between nanoparticles and biomolecules, which will be in favor of predicting the biological toxicity of nano-DDS and engineering functionalized nanocarriers.

The intracellular fate and transport mechanism of shape, size and rigidity varied nanocarriers for understanding their oral delivery efficiency

Nanocarriers have become an effective strategy to overcome epithelial absorption barriers. During the absorption process, the endocytosis mechanisms, cell internalization pathways, and transport efficiency of nanocarriers are greatly impacted by their physical properties. To understand the relationship between physical properties of nanocarriers and their abilities overcoming multiple absorption barriers, nanocarriers with variable physical properties were prepared via self-assembly of hydrolyzed α-lactalbumin peptide fragments. The impacts of size, shape, and rigidity of nanocarriers on epithelial cells endocytosis mechanisms, internalization pathways, transport efficiency, and bioavailability were studied systematically. The results showed that nanospheres were mainly internalized via clathrin-mediated endocytosis, which was then locked in lysosomes and degraded enzymatically in cytoplasm. While macropinocytosis was the primary pathway of nanotubes and transported to the endoplasmic reticulum and Golgi apparatus, resulting in a high drug concentration and sustained release in cytoplasm. Besides, nanotubes can overcome the multi-drug resistance by inhibiting the P-glycoprotein efflux. Furthermore, nanotubes can open intercellular tight-junctions instantaneously and reversibly, which promotes transport into blood circulation. The aqueous solubility of hydrophobic bioactive mangiferin (Mgf) was improved by nanocarriers. Most importantly, the bioavailability of Mgf was the highest for cross-linked short nanotube (CSNT) which outperformed free Mgf and other formulations by in vivo pharmacokinetic studies. Finally, Mgf-loaded CSNT showed an excellent therapeutic efficiency in vivo for the intervention of streptozotocin-induced diabetes. These results indicate that cross-linked α-lactalbumin nanotubes could be an effective nanocarrier delivery system for improving the epithelium cellular absorption and bioavailability of hydrophobic bioactive compounds.