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The nano-delivery system with a dual biomimetic effect can penetrate deeper in tumor microenvironments (TMEs) and release sufficient antitumor drugs, which has attracted much attention. In this study, we synthesized erythrocyte-like mesoporous silica nanoparticles (EMSNs) as the core loaded with doxorubicin (DOX) and coated them with calcium phosphate (CaP) and erythrocyte membrane (EM) to obtain DOX/EsPMs. The transmission electron microscopy (TEM), fluorescent co-localization and protein bands of SDS-PAGE were used to confirm the complete fabrication of EsPMs. The EsPMs with erythrocyte-like shape exhibited superior penetration ability in in vitro diffusion and tumor-sphere penetration experiments. Intracellular Ca2+ and ROS detection experiments showed that the CaP membranes of EsPMs with pH-sensitivity could provide Ca2+ continuously to induce reactive oxide species' (ROS) generation in the TME. The EM as a perfect "camouflaged clothing" which could confuse macrophagocytes into prolonging blood circulation. Hemolysis and non-specific protein adsorption tests proved the desirable biocompatibility of EsPMs. An in vivo pharmacodynamics evaluation showed that the DOX/EsPMs group had a satisfactory tumor-inhibition effect. These advantages of the nano-erythrocytes suggest that by modifying the existing materials to construct a nano-delivery system, nanoparticles will achieve a biomimetic effect from both their structure and function with a facilitated and sufficient drug release profile, which is of great significance for antitumor therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSNs) have been widely used in biomedical applications. However, most studies have been limited to spherical MSNs, while non-spherical MSNs have never been rigorously studied. In this study, we fabricated mesoporous silica nanospheres (MSNSs) and mesoporous silica nanorods (MSNRs), with different aspect ratios (ARs) but identical surface chemistries to explore the shape effects of MSNs on oral delivery. The results of cellular studies demonstrated that MSNRs exhibited a higher cellular uptake than MSNSs. Mechanistic studies showed that caveolae-mediated endocytosis was involved in the uptake of MSNRs, while the clathrin-dependent pathway contributed to the endocytosis of MSNSs. Meanwhile, the apparent permeability coefficient value (Papp) of doxorubicin hydrochloride (Dox)-loaded MSNRs was approximately 1.8-, 3.2- and 6.3-fold higher than that of Dox-loaded MSNS1, Dox-loaded MSNS2 and Dox solution, respectively. The in vivo pharmacokinetics study showed that the area under the plasma concentration-time curve (AUC) achieved by Dox-loaded MSNRs was 1.9-, 3.4- and 5.7-fold higher than the corresponding values for Dox-loaded MSNS1, MSNS2 and Dox solution, respectively. Taken together, our results demonstrated that tuning nanoparticle shape potentially determines the biological fate of nanoparticles with higher delivery efficiency, such as enhanced cellular uptake and oral bioavailability. [ABSTRACT FROM AUTHOR]

This work explored absorption efficacy via an in vivo imaging system and parallel artificial membrane penetration in indomethacin (IMC) solid dispersion (SD) systems. Two different polymer excipients—hydroxypropyl methylcellulose (HPMC) and Kollicoat IR as precipitation inhibitors (PIs)—combined with mesoporous silica nanoparticles (MSNs) as carriers were investigated. The IMC–SDs were prepared using the solvent evaporation method and characterized by solubility analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), and differential scanning calorimetry (DSC). It was confirmed that IMC successfully changed into an amorphous state after loading into the designed carriers. The in vitro release and stability experiments were conducted to examine the in vitro dissolution rates of IMC–SDs combined with HPMC and Kollicoat IR as PIs which both improved approximately three-fold to that of the pure drug. Finally, in vivo studies and in vitro parallel artificial membrane penetration (PAMPA) experiments ensured the greater ability of enhancing the dissolution rates of pure IMC in the gastrointestinal tract by oral delivery. In brief, this study highlights the prominent role of HPMC and Kollicoat IR as PIs in MSN SD systems in improving the bioavailability and gastrointestinal oral absorption efficiency of indomethacin. [ABSTRACT FROM AUTHOR]

The use of mesoporous silica nanoparticles (MSNs) in the field of oral drug delivery has recently attracted greater attention. However, there is still limited knowledge about how the shape of MSNs affects drug delivery capacity. In our study, we fabricated mesoporous silica nanorods (MSNRs) to study the shape effects of MSNs on oral delivery. MSNRs were characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infrared spectroscopy (FTIR), and small-angle X-ray diffraction (small-angle XRD). Indomethacin (IMC), a non-steroidal anti-inflammatory agent, was loaded into MSNRs as model drug, and the drug-loaded MSNRs resulted in an excellent dissolution-enhancing effect. The cytotoxicity and in vivo pharmacokinetic studies indicated that MSNRs can be applied as a safe and efficient candidate for the delivery of insoluble drugs. The use of MSNs with a rod-like shape, as a drug delivery carrier, will extend the pharmaceutical applications of silica materials. [ABSTRACT FROM AUTHOR]

Abstract Herein, three kinds of mesoporous silica nanoparticles (BMSs) were biomimetically synthesized by using heterocyclic amino acid derivatives as template and their the basic capacity in being drug carriers that covered structure, wettability, degradation, brain uptake, hemocompatibility and toxicity were systematically evaluated. The results indicated that BMSs were kinds of spherical nanoparticles with good biocompatibility. Their in vitro and in vivo behaviors, including degradation, biodistribution and biocompatibility were mainly governed by the wettability which was closely related to the structure and pore diameter of mesoporous silica nanoparticles. BMSs can degrade completely under simulated physiological environments through a time period of 2–13 weeks. They showed the tendency of brain distribution, and the distribution amount peaked at 4 h post administration. Particularly, Trp-BMS (BMS templated by C 16 - l -tryptophan) with the largest amount of OH groups on the surface exhibited highest wettability, fastest degradation rate and the lowest brain distribution ability. Besides, His-BMS (BMS templated by C 16 - l -histidine) and Pro-BMS (BMS templated by C 16 - l -poline) were silica materials with good biocompatibility. Both in vitro and in vivo studies uncovered no significantly toxicity for BMSs and they were proved to be safe when they circulated into the blood. However, Trp-BMS might induce severe hemolysis and cell cycle arrest due to the high wettability. It is believed that appropriate wettability is required for the in vivo application of nanomaterials and the in vivo evaluation of mesoporous silica nanoparticles will provide useful information for understanding the underlining toxicity of biomaterials and bring new insights on designing efficient drug delivery systems. Graphical abstract Unlabelled Image Highlights • Biomimetically synthesized mesoporous silicas (BMSs) were kinds of nanoparticles with good biocompatibility and low toxicity. • The in vitro and in vivo behaviors of BMSs were mainly governed by their wettability. • The smaller the pore size was, the higher the density of –OH group was, the smaller the contact angle was. • BMSs can degrade completely under simulated physiological environments. • BMSs showed the tendency of brain distribution. [ABSTRACT FROM AUTHOR]

In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design. [ABSTRACT FROM AUTHOR]

As is well known to all, delivering drug precisely to the tumor site is beneficial to improve antitumor effect. In this study, we reported mesoporous silica nanoparticles (MSNs) coated with dual-film of calcium carbonate (CaCO 3) and lipid bilayer (denoted as MSNs@CaCO 3 @liposomes) innovatively which achieve sustained drug release anchored at tumor microenvironment and enhanced biocompatibility. The pH-sensitive CaCO 3 film acted as a guide to cap the pore channels of MSNs allowed pH-triggered drug release when transporting into cancer cells. Furthermore, MSNs@CaCO 3 was capsuled by lipid bilayer to improve cellular uptake efficiency and biocompatibility in blood circulation. Morphology of nanoparticles was characterized by transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) to confirm that double films were coated successfully. Doxorubicin hydrochloride (DOX) was efficaciously loaded into mesoporous pores as a model drug with a high drug loading content of 28%, forming DOX-loaded MSNs@CaCO 3 @liposomes (DOX/MSNs@CaCO 3 @liposomes). Non-specific protein adsorption and hemolysis test revealed enhanced biocompatibility. Drug release study in vitro showed DOX/MSNs@CaCO 3 @liposomes could delay to release DOX at pH 5.0 and avoid releasing at pH 7.4. In vitro and in vivo antitumor efficiency evaluation showed that DOX/MSNs@CaCO 3 @liposomes have a desirable inhibitory activity on tumor growth. Therefore, dual-film coated MSNs could be a good candidate for an antitumor drug delivery system. [Display omitted] • pH-sensitivity of calcium carbonate and biocompatibility of liposome were combined in one drug delivery system. • DOX/MSNs@CaCO 3 @liposomes could decrease side effect. • DOX/MSNs@CaCO 3 @liposomes exhibited delayed drug release in six days. [ABSTRACT FROM AUTHOR]