Desolvation Method Research Articles

Application of a simple desolvation method to increase the formation yield, physical stability and hydrophobic drug encapsulation capacity of chitosan-based nanoparticles

As one of the classical nano drug carriers, chitosan-based nanoparticles (CsNps) are getting increasing attentions for their non-toxicity, biocompatibility and biodegradability. The ionotropic gelation is the most favorable method for CsNps preparation, while it’s beset by some issues, i.e. low particle formation yield, poor physical stability and low hydrophobic drug loading capacity. To solve these problems, a simple desolvation method was attempted in this study for CsNps preparation. Using this method, an increased formation yield of CsNps (about 100%) could be obtained, and after diluting the particles by various buffers (PBS 7.0, 7.4 and 8.0, DMEM medium and 1640 medium), an improved stability in diameter could be observed. The drug loading results showed paclitaxel loading efficiency of 9.8% could be obtained when the ratio of paclitaxel to Cs was set at 0.2, higher than the ionotropic gelation method (0.43%). The particles formation mechanisms were studied by the molecular dynamics simulation, and the results showed the Lennard-Jones interaction of Cs-Cs, which could be adjusted by the pH value of system, played a great role in formation of particles with the desolvation method. This study provided an alternative preparation technology for CsNps with high process yield, physical stability and hydrophobic drug encapsulation capacity.

Preparation of gelatin nanoparticles by two step desolvation method for application in photodynamic therapy

Gelatin nanoparticles have recently been receiving considerable attention because they offer a good option as release systems due to their low cost, biocompatibility, biodegradability and its application in several types of formulations. This study aim was to evaluate the potential application of gelatin nanoparticles entrapping a photosensitizer in Photodynamic Therapy. Gelatin nanoparticles were studied by steady-state techniques and the biological activity evaluated by in vitro MTT assay. The particles were spherical in shape exhibiting a 273 nm diameter with a low tendency to aggregate. The loading efficiency was 76%. Photosensitizer photophysical properties were shown to be preserved after GN encapsulation. The cells viability obtaining 85% cells death compared with control. The results demonstrate that gelatin nanoparticles can be successfully applied for photosensitizers encapsulation or other active drugs and be used as an optimal medium for a variety of bioactive materials, which can also be encapsulated by the proposed method.

Copper-Free 'Click' Chemistry-Based Synthesis and Characterization of Carbonic Anhydrase-IX Anchored Albumin-Paclitaxel Nanoparticles for Targeting Tumor Hypoxia.

Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of the logical and economical approaches is to develop a tumor hypoxia-targeting drug formulation platform for selective delivery of payload to the drug-resistant and invasive cell population of TNBC tumors. Toward this, we developed a Carbonic Anhydrase IX (CA IX) receptor targeting human serum albumin (HSA) carriers to deliver the potent anticancer drug, Paclitaxel (PTX). We used Acetazolamide (ATZ), a small molecule ligand of CA IX to selectively deliver HSA-PTX in TNBC cells. A novel method of synthesis involving copper free ‘click’ chemistry (Dibenzocyclooctyl, DBCO) moiety with an azide-labeled reaction partner, known as Strain-Promoted Alkyne Azide Cycloaddition (SPAAC) along with a desolvation method for PTX loading were used in the present study to arrive at the CA IX selective nano-carriers, HSA-PTX-ATZ. The anticancer effect of HSA-PTX-ATZ is higher compared to HSA, PTX and non-targeted HSA-PTX in MDA-MB-231 and MDA-MB-468 cells. The cell killing effect is associated with induction of early and late phases of apoptosis. Overall, our proof-of-concept study shows a promising avenue for hypoxia-targeted drug delivery that can be adapted to several types of cancers.

Inulin hydrolysis by inulinase immobilized covalently on magnetic nanoparticles prepared with wheat gluten hydrolysates

Inulinase can produce a high amount of fructose syrup from inulin in a one-step enzymatic process. Inulinase from Aspergillus niger was immobilized covalently on Fe3O4 magnetic nanoparticles functionalized with wheat gluten hydrolysates (WGHs). Wheat gluten was enzymatically hydrolyzed by two endopeptidases Alcalase and Neutrase and related nanoparticles were prepared by desolvation method. Magnetite nanoparticles were coated with WGHs nanoparticles and then inulinase was immobilized onto it using glutaraldehyde as crosslinking agent. Parallel studies employing differential scanning calorimetry and field emmision scanning electron microscopy were carried out to observe functional and structural variations in free inulinase during immobilization. Optimum temperature of immobilized inulinase was increased, while, pH and Km values were decreased compared to free enzyme. Overall, a 12.3 folds rise was detected in enzyme half-life value after Immobilization at 75 °C and enzyme preserved 70% of its initial activity after 12 cycles of hydrolysis with 75% of enzyme loading.

Recent Advances in Preparation and Modification of Gelatin Nanoparticles for Pharmaceutical Applications

Nanoparticles can be produced from the proteinaceous materials called gelatin. Gelatin is extracted from collagen of skin, bones, and connective tissues by controlled acidic or basic hydrolysis. This paper focuses on several methods developed for preparing and modifying gelatin nano-particles (GNPs) for delivery of gene and drugs. In general, eight methods are being used for producing GNPs: the coacervation method; the two step desolvation method; the complex coacervation process; the solvent extraction or emulsion process; the nanoprecipitation method; the microemulsion method; the inverse miniemulsion technique and self-assembly method. The problem of being phagocytosized by the mononuclear phagocyte system (MPS) in the body is among the limitations of native GNPs encounter. The interest was based on the facts that gelatin has been known for its low immunogenicity for many years and is administered intravenously since it is an ingredient of various registered blood substitutes. The advantage offered by the amino acid side-chains of the gelatin matrix molecule is the option of multiple further modifications. Hence, GNPs’ surface modification is typically needed to tackle phagocytosis. Many researchers have reported the gelatin use for anticancer drugs delivery, gene delivery, pulmonary drug delivery, ocular drug delivery and protein delivery.

Preparation, Physico-Chemical Characterization and Pharmacodynamics of Ceftriaxone Loaded BSA Nanoparticles

The aim of the present study was to develop and characterize ceftriaxone loaded BSA nanoparticles. The nanoparticles were prepared by desolvation method. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and fourier transform infrared (FT-IR) characterization of the synthesized nanoparticles was done. SEM and TEM revealed that the nanoparticles had a smooth and spherical surface and FT-IR revealed that there was no interaction between the drug and the polymer. Encapsulation efficacy of nanoparticles was 44.8%. The mean particle size of BSA obtained was 149.46 ± 1.05 nm, PDI was 0.09 and the zeta potential was -28 mV. In vitro drug release at pH 7.4 was found to be 85.8% at 12 h time period. Various mathematical models were used and the values nearest to R2 were evaluated. Model fitting revealed that it followed the Higuchi and Korsmeyer Peppas Model. The values of R were higher for Higuchi and Korsmeyers peppas model. Pharmacodynamic studies were done, for S. aureus the results of MIC and MBC of Drug were 2.51 μg and 3 μg. The results of MIC and MBC of sample were 1.51 μg and 2.1 μg and for E. coli the results of MIC and MBC of Drug were 0.05 μg and 0.08 μg. The results of MIC and MBC of sample were 0.05 μg and 0.05 μg.

The Wonders of Silk Fibroin Biomaterials in the Treatment of Breast Cancer.

Breast cancer has continued to be a cause of increasing morbidity and mortality in women, being the most common cause of cancer-related deaths among them. Its management using chemotherapy is continually plagued with problems of systemic toxicity, lack of compliance by patients, and inadequate targeting of cancer cells. The future of breast cancer chemotherapy will likely involve the use of biocompatible high cell-targeting capacity drug-delivery vehicles like silk fibroin to ameliorate these problems. The utilization of silk fibroin nanoparticles to deliver cytotoxic drugs provides specificity, optimal entrapment, improved therapeutic index, and maximal breast cancer cell toxicity with minimal or no collateral damage to surrounding normal cells. The silk fibroin obtained from the cocoon of the Bombyx morii worm is processed and degummed to remove the sericin component; it is then made into nanoparticles utilizing the desolvation, ionic gelation, or electrospray method. It is then loaded with an appropriate chemotherapeutic drug (e.g., carboplatin), and characterization is performed using physico-chemical methods such as fourier-transform infrared spectroscopy, dynamic light scattering, or transmission electron microscopy. The nanoparticles are then tested for cytoxicity, and the induction of apoptosis on breast cancer cell lines MC-7 (Her2-) and MDA-MB-453 (Her2+). Toxicity and apoptosis are assessed using the MTT assay and ELISA methods, respectively. Silk fibroin has been demonstrated in various studies to be a very useful tool in specific active or passive drug delivery to target cancer cells, thus ensuring a maximum destruction and minimum damage to normal surrounding cells, which decreases systemic toxicity and enhances drug efficacy.

The Antibacterial and Antioxidant Activity of Centella Asiatica Chloroform Extract-loaded Gelatin Nanoparticles

Nanoencapsulation of Centella asaitica (CA) crude chloroform extract seems to be an attractive approach that may improve drug bioavailability and drug delivery system. In the study, CA extract-loaded gelatin nanoparticles (CGNP) were developed by gelatin one-step and two-step desolvation methods, using three different ratios between CA crude chloroform extract and gelatin (1:2, 1:3, and 1:4 w/w). The antibacterial and antioxidants activities of CGNP and CA were compared. The antioxidant activity of CGNP and CA was evaluated by using DPPH radical scavenging assay and ferric reducing antioxidant power (FRAP) assay. Results showed an enhancement of CGNP antibacterial activity against food borne pathogen. The highest inhibition diameters and FRAP determined from CGNP prepared by one-step at 1:4 ratios (1.03±0.39 cm and 1.23±019 mmol Fe2+/mg dried weight, respectively). However, CGNP was no significant difference in DPPH radical scavenging activity compared to CA. These results provide useful information for developing effective nanoencapsulation of CA as effective natural ingredient.

Chitosan-stablized bovine serum albumin nanoparticles having ability to control the release of NELL-1 protein

The study was designed to prepare and evaluate chitosan stabilized-albumin nanoparticles as NELL-1 protein carriers(Chi/NNPs). The Chi/NNPs were prepared by desolvation method and then stabilized by chitosan through electrostatic interaction. The Chi/NNPs were characterized for drug loading efficiency, surface morphology, particle size, surface charge. Fluorescein isothiocyanate-labeled chitosan was used to confirm the homogeneity of chitosan coating on the BSA nanoparticles. The NELL-1 bioactivity of Chi/NNPs and the release kinetics were investigated in vitro. It was observed that the mean particle size with chitosan (0.075 wt%,0.15 wt%, 0.3 wt%, respectively) and the surface charge were 368.663 ± 15.470 nm, 382.881 ± 18.767 nm, 390.480 ± 11.465 nm and +25.03 ± 1.42 mV, +30.27 ± 1.80 mV, +31.03 ± 2.05 mV respectively. Drug entrapment efficiency ranged from 87.83% to 89.30%. The Chi/NNPs prepared with the 0.15 wt% chitosan were able to successfully control the release of NELL-1 and maintain a sustained release for up to 8 days. Furthermore, more than 82.67 ± 8.74% of the loaded protein’s bioactivity was preserved in Chi/NNPs over the period of the investigation. Our findings suggest that Chi/NNPs as promising protein delivery nanocarriers have the ability to maintain sustained release kinetics and to preserve the bioactivity of released NELL-1.

Improved delivery of the anticancer agent citral using BSA nanoparticles and polymeric wafers.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, with a 5-year survival rate of between 30 and 65%. Standard treatment involves surgery, radiation treatment, and chemotherapy. However, there is a high recurrence rate, particularly from locoregional spread. We investigated the use of the natural compound citral (3,7-dimethyl-2,6-octadienal), which can be found in a number of plants, but is particularly abundant in lemon grass (Cymbopogon citratus) oil, for activity against immortalized RMS cells. Significant cancer cell death was seen at concentrations above 150 μM citral, and mitochondrial morphological changes were seen after incubation with 10 μM citral. However, since citral is a highly volatile molecule, we prepared albumin particles by a desolvation method to encapsulate citral, as a means of stabilization. We then further incorporated the loaded nanoparticles into a biodegradable polyanhydride wafer to generate a slow release system. The wafers were shown to degrade by 50% over the course of 25 days and to release the active compound. We therefore propose the use of the citral-nanoparticle-polymer wafers for implantation into the tumor bed after surgical removal of a sarcoma as a means to control locoregional spread due to any remaining cancerous cells.

Development of Acyclovir-Loaded Albumin Nanoparticles and Improvement of Acyclovir Permeation Across Human Corneal Epithelial T Cells.

The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovine serum albumin (BSA) nanoparticles as well as to assess their in vitro transcorneal permeation across human corneal epithelial (HCE-T) cell multilayers. The ACV-loaded BSA nanoparticles were prepared by desolvation method along with physicochemical characterization, cytotoxicity, as well as in vitro transcorneal permeation studies across HCE-T cell multilayers. The nanoparticles appeared to be spherical in shape and nearly uniform in size of about 200 nm. The size of nanoparticles became smaller with decreasing BSA concentration, while the ratios of water to ethanol seemed not to affect the size. Increasing the amount of ethanol in desolvation process led to significant reduction of drug entrapment of nanoparticles with smaller size and more uniformity. The ACV-loaded BSA nanoparticles prepared were shown to have no cytotoxic effect on HCE-T cells used in permeation studies. The in vitro transcorneal permeation results revealed that ACV could permeate through the HCE-T cell multilayers significantly higher from BSA nanoparticles than from aqueous ACV solutions. The ACV-loaded BSA nanoparticles could be prepared by desolvation method without glutaraldehyde in the formulation. ACV could increasingly permeate through the multilayers of HCE-T cells from the ACV-loaded BSA nanoparticles. Therefore, the ACV-loaded BSA nanoparticles could be a highly potential ocular drug delivery system.

Preparation of magnetic albumin nanoparticles via a simple and one-pot desolvation and co-precipitation method for medical and pharmaceutical applications

In this study, iron oxide magnetic bovine serum albumin core–shell nanoparticles (BSA coated IONPs) with narrow particle size distribution were synthesized under one-pot reaction via the desolvation and chemical co-precipitation method. Functionalized IONPs were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques. Furthermore, vibrating sample magnetometer (VSM) analysis show these nanoparticles (NPs) have an excellent magnetic properties. Cellular toxicity of IONPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared core-shell NPs were performed. The presence of albumin as a biomolecule coating on the surface of IONPs showed an improving effect to reduce the cytotoxicity. The properties of the designed NPs propose the BSA coated IONPs as a promising candidate for multifunctional biomedical applications.

Doughnut-shaped bovine serum albumin nanoparticles loaded with doxorubicin for overcoming multidrug-resistant in cancer cells

Traditional spherical albumin nanoparticles remain as the dominant shape of nano-carriers described in the literature at present, due to their simple desolvation method of synthesis. However, non-spherical shapes also show great promise as cancer drug delivery vectors. In this study, we report a novel synthetic strategy based on dimethyl sulfoxide (DMSO) addition during desolvation step, to produce doughnut-shaped bovine serum albumin nanoparticles (DBSA-NPs), while maintaining narrow size distributions and homogeneity. The characteristics such as size, polydispersity and doxorubicin loading of prepared DBSA-NPs in comparison with spherical ones were determined. The biodegradation of DBSA-NPs loaded with doxorubicin (Dox-DBSA-NPs) in the presence of trypsin enzyme was spectrophotometrically monitored directly based on doxorubicin release profile. The release profile was analyzed with different kinetic models and it was best fitted with Higuchi kinetics model. The anticancer effect of Dox-DBSA-NPs against lymphoblastic leukemia (MOLT-4) and multidrug resistant uterine sarcoma (MES-SA/DX-5) cell lines were also investigated and the results were comparable with doxorubicin loaded spherical BSA nanoparticles. These results showed the potential of Dox-DBSA-NPs as a novel and high potential nano-carrier for management of non-resistance and also multidrug resistant cancer cells.

Preparation, characterization and application of haemoglobin nanoparticles for detection of acrylamide in processed foods

The nanoparticles of haemoglobin (HbNPs) were prepared by desolvation method and characterized by transmission electron microscopy (TEM),UV–vis spectroscopy, Fourier transformation infra red (FTIR) spectroscopy and X-ray diffraction (XRD) and atomic force microscopy (AFM). Protein profile of HbNPs was also studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). An amperometric acrylamide biosensor was constructed by immobilizing covalently HbNPs onto polycrystalline Au electrode. The Au electrode was characterized by scanning electron microscopy (SEM) and electrochemical impedance spectra (EIS) before and after immobilization of HbNPs. The biosensor showed optimum current response within 2s at 0.26V, pH 5.0 at room temperature (20°C). The biosensor measured the acrylamide concentration in processed foods. The working range of biosensor was 0.1nm–100mM with a limit of detection (LOD) as low as 0.1nM. The biosensor measured acrylamide concentration in various processed foods such as biscuits, bread, potato crisps, “kurkure”, nuts and fried cereals. The analytical recovery of added acrylamide in aqueous extract of food at 5 and 10mM was 99% and 98% respectively. Within-and between-batch, co-efficient of variations were 3.85% and 4.67% respectively. The structural analogs of acrylamide such as acrylic acid and propionic acid had practically no interference on the biosensor.

Preparation and characterization of cardamom extract-loaded gelatin nanoparticles as effective targeted drug delivery system to treat glioblastoma

The purpose of this research study was to prepare and characterize cardamom extract-loaded gelatin nanoparticles (CE-loaded GNPs) with a diameter ≤200nm as a potent drug delivery system (DDS) for treatment of glioblastoma, which is the most common and aggressive type of brain tumor. The BBB poses physical and biological limitations to drug diffusion to reach target tissues. Polymeric nanoparticles, like gelatin, are suitable vehicles for drug delivery into the central nervous system (CNS). They are able to cross the BBB. Hence, we prepared CE-loaded GNPs by a two-step desolvation method. Seizures are detrimental secondary effects of brain tumors. Therefore, we used cardamom extract, which is an herbal anticancer and antiepileptic drug without any side effects, instead of synthetic drugs to load in gelatin nanoparticles during the particles preparation. We also prepared gelatin Type A and Type B nanoparticles for size comparison. Encapsulation efficiency, mean particle size, zeta potential and in vitro release profile were performed, and particle size analysis, dynamic light scattering (DLS), UV–Vis spectrophotometry, differential scanning calorimetry (DSC), X-Ray diffraction (XRD), scanning electron microscopy (SEM) and field emission scanning electron microscopy (FE-SEM) were employed to evaluate structural and physicochemical properties of the samples. CE-loaded GNPs were obtained with diameters of 40–200nm, zeta potential of −40.1mV and entrapment efficiency (EE) of 70%. The ratio of extract to polymer, 1:20, was revealed to be more suitable in obtaining smaller nanoparticles without any precipitate or aggregation. We also examined cytotoxic effects of CE and CE-loaded GNPs on human glioblastoma cancer U87MG cells.

Erlotinib-loaded albumin nanoparticles: A novel injectable form of erlotinib and its in vivo efficacy against pancreatic adenocarcinoma ASPC-1 and PANC-1 cell lines

Erlotinib was loaded on albumin nanoparticles for the first time and the cytotoxic effect of the resulting nanoparticles against ASPC-1 and PANC-1 pancreatic adenocarcinoma cell lines was evaluated. The carrier (albumin nanoparticles, ANPs) was synthesized by desolvation method using a mixed solvent followed by thermal crosslinking for stabilization. ANPs and the drug-loaded ANPs were characterized by field emission scanning and transmission electron microscopies, particle size analysis and Fourier transform infrared spectroscopy. The nanoformulation had a size of <14nm with a good monodispersity. Drug loading and encapsulation efficiencies were evaluated as 27 and 44%. Cytotoxicity assays after 72h revealed the potential of ANPs to improve erlotinib toxicity (54% against 34% of free drug toward ASPC-1 cell line, and 52% against 30% toward PANC-1 cell line). Values of IC50 were obtained for both cell lines and indicated significant reduction in the erlotinib dose necessary for killing the cells, while, ANPs were completely safe. The results demonstrated that erlotinib-loaded ANPs had a remarkable potential for pancreatic cancer drug delivery.

Hardly water-soluble drug-loaded gelatin nanoparticles sustaining a slow release: preparation by novel single-step O/W/O emulsion accompanying solvent diffusion.

Paclitaxel (PTX)-loaded gelatin nanoparticles (NPs) were prepared, for the first time, by novel O/W/O emulsion with a single-step emulsion process accompanying solvent diffusion, in contrast to the conventional double-step emulsion processes. Linoleic acid was chosen among the natural fatty acids as the exterior medium for the single-step emulsion process accompanying solvent diffusion. The size mean and zeta potential of the PTX-loaded gelatin NPs in their suspension were 164.95nm (±6.43nm) distributed with a polydispersity of 0.074 (±0.046) and -23.85mV (±12.66mV), respectively. The size of the PTX-loaded gelatin NPs prepared in this study was the smallest among the reported sizes of PTX-loaded gelatin NPs, which would contribute to the enhanced permeability and retention (EPR). In addition, TEM showed that the loaded PTX was located mostly inside the gelatin NPs unlike previous investigations. Accordingly, the conceptual model of the designed PTX-loaded gelatin nanoparticle was introduced. Sustaining a slow PTX release on a day-time scale without an initial burst release into a release medium was observed along with a delay of more than 2days (i.e., 50h) before a bursting PTX release from 50 to 70h despite the addition of a protein degrading enzyme. The observed PTX-loading efficiency was 54.5%. This loading efficiency was greater than that of previous study using gelatin of bloom 75-100 of Lu et al. to prepare PTX-loaded gelatin NPs using a desolvation method.

An amperometric H2O2 biosensor based on hemoglobin nanoparticles immobilized on to a gold electrode.

The nanoparticles (NPs) of hemoglobin (Hb) were prepared by desolvation method and characterized by transmission electron microscopy (TEM), UV spectroscopy and Fourier-transform IR (FTIR) spectroscopy. An amperometric H2O2 biosensor was constructed by immobilizing HbNPs covalently on to a polycrystalline Au electrode (AuE). HbNPs/AuE were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectra (EIS) before and after immobilization of HbNPs. The HbNPs/AuE showed optimum response within 2.5 s at pH 6.5 in 0.1 M sodium phosphate buffer (PB) containing 100 μM H2O2 at 30°C, when operated at –0.2 V against Ag/AgCl. The HbNPs/AuE exhibited Vmax of 5.161 ± 0.1 μA cm−2 with apparent Michaelis-Menten constant (Km) of 0.1 ± 0.01 mM. The biosensor showed lower detection limit (1.0 μM), high sensitivity (129 ± 0.25 μA cm−2 mM−1) and wider linear range (1.0–1200 μM) for H2O2 as compared with earlier biosensors. The analytical recoveries of added H2O2 in serum (0.5 and 1.0 μM) were 97.77 and 98.01% respectively, within and between batch coefficients of variation (CV) were 3.16 and 3.36% respectively. There was a good correlation between sera H2O2 values obtained by standard enzymic colorimetric method and the present biosensor (correlation coefficient, R2 =0.99). The biosensor measured H2O2 level in sera of apparently healthy subjects and persons suffering from diabetes type II. The HbNPs/AuE lost 10% of its initial activity after 90 days of regular use, when stored dry at 4°C.

Release behavior and signaling effect of vitamin D3 in layered double hydroxides-hydroxyapatite/gelatin bone tissue engineering scaffold: An in vitro evaluation

Incorporating the controlled release of vitamin D3 (VD3) into biodegradable porous scaffolds is a new approach to equipping multifunctional therapeutics for osteoporosis. The current investigation involves the encapsulation of VD3 into gelatin through the one-step desolvation method. The layered double hydroxides-hydroxyapatite nanocomposite (LDH-HAp) and pure LDH were combined with the gelatin-VD3 complex to reinforce the porous biodegradable structure and enhance the biological response. Afterwards, glutaraldehyde was used to form crosslinks within the gelatin chains. The encapsulation efficiency and loading capacity showed approximately 40% and 50% reduction after crosslinking, respectively. The particle size, zeta potential, contact angle, Young’s modulus and porosity were measured to find the effect of VD3 on the scaffolds’ physiochemical properties. To explore the bioactivity and degradation behavior, the scaffolds were immersed in simulated body fluid. The VD3 release kinetics followed the Korsmeyer-Peppas model and non-Fickian release pattern. The greater osteblastic expression was observed in VD3-containing scaffolds due to the higher alkaline phosphatase activity which was excited more by HAp (P<0.05). Alizarin red staining illustrated that VD3 induced more calcium deposition, which indicates the signaling role of VD3 on osteoconductivity and biomineralization. The findings provide new insights on the VD3 encapsulation within hydrophilic matrices to protect VD3 and enable the signaling ability for bone tissue engineering scaffolds, which could improve the bone healing efficiency.

Bufalin-loaded bovine serum albumin nanoparticles demonstrated improved anti-tumor activity against hepatocellular carcinoma: preparation, characterization, pharmacokinetics and tissue distribution.

ObjectiveTo prepare and evaluate the liver-targeted drug delivery system of Bufalin with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.MethodsBufalin-loaded bovine serum albumin nanoparticle was prepared by desolvation method, to investigate the in vitro release performance and to evaluate the pharmacokinetic and tissue distribution. The antitumor activity against hepatocellular carcinoma was evaluated in vitro and in vivo, respectively.ResultsThe Bufalin-loaded bovine serum albumin nanoparticle with an average particle size of 125.1 nm exhibited a sustained release behavior in vitro. The half-life, blood plasma area under the curve and apparent volume of distribution of Bufalin-loaded bovine serum albumin nanoparticle were significantly higher than that of Bufalin, whereas the clearance rate was lower than Bufalin group. The uptake of liver for Bufalin-loaded bovine serum albumin nanoparticle was 352.045 ± 35.665 ng/g while for Bufalin was 164.465 ± 48.080 ng/g (P < 0.01) at 5 min. The uptake of tumor for Bufalin-loaded bovine serum albumin nanoparticle was significantly higher than that of Bufalin both at 5 min (50.169 ± 11.708 ng/g, 93.415±13.828 ng/g, P < 0.01) and 15 min (43.683 ± 11.499 ng/g, 64.219 ± 17.684 ng/g, P > 0.05). Bufalin-loaded bovine serum albumin nanoparticle and Bufalin have similar antitumor activity in vitro. The tumor inhibition effect of Bufalin-loaded bovine serum albumin nanoparticle was stronger than that of Bufalin alone in vivo.ConclusionBufalin-loaded bovine serum albumin nanoparticle is a promising liver-targeted drug delivery system with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.