Drug Loading Amount Research Articles

Polysaccharide and monosaccharide guided liver delivery of Sorafenib Tosylate – A nano-strategic approach and comparative assessment of hepatospecificity

Hepatospecific delivery by ligand based receptor targeting is an established strategy to augment therapy associated with liver diseases and disorders. Previously, we have investigated the effect of ligand headgroup on cellular uptake mediated by the asialoglycoprotein receptor by in silico and in vitro approach. In this paper, we report the design of agarose based liposomes for delivery to liver cancer cells and provide a proof of concept of the targeting efficiency against galactose liposomes using an in vivo approach. Sorafenib Tosylate loaded targeting liposomes were developed and optimized using factorial design. Comparative evaluation including cell cytotoxicity, pharmacokinetics and biodistribution and hepatospecific uptake was performed for both the liposomal systems. The formulations possessed a particle size of 150 – 180 nm and a zeta potential of 30 - 60 mV depending on the amount of ligand and drug loading, with more than 90% entrapment efficiency. A two-fold increase in cytotoxicity was observed with agarose-based liposomes as compared to galactose based liposomes. In vivo PK evaluation indicated a reduction in half life of drug when loaded in agarose ligand loaded system, probably due to greater uptake in the liver as evidenced in biodistribution study. Intrahepatic disposition revealed a higher PC/NPC uptake ratio with the targeted systems as compared to conventional liposomes, although the agarose-based system resulted in highest uptake ratio. A biocompatible platform for specific delivery of drugs to hepatocytes was established validating a rational approach to design liver targeting systems.

Cumulative release kinetics of levothyroxine-Na pentahydrate from chitosan/arabinogalactane based pH sensitive hydrogel and it's toxicology

In the study, a new hydrogel was synthesized by the freeze method of chitosan and arabinogalactan. The structure of the gel was characterized by SEM, XRD, TGA, and the interaction of macromolecules was determined. Swelling kinetics and degradation of hydrogel were studied. It was found that in the oxidizing medium, the degradation of the gel is 64% in 2 weeks, and in the elastase and PBS medium is about 19–22%. The hormone-substituted levothyroxine-Na pentahydrate was sorbed into the synthesized gel 50–200 μg depend on biopolymer mass ratio and studied for release in various media. It has been shown that the favourable yield (75–92%) and drug loading amount (40–220 μg) towards levothyroxine for all gel samples allows the use of chitosan based matrix for the delivery and controlled release of levothyroxine-Na. It was found that the controlled release of the levothyroxine-Na from the chitosan/arabinogalactan-based hydrogel to be consistent with the Hixson-Crowell, Korsmeyer-Peppas and Higuchi kinetic models, depending on the mole ratio of the polymers and the amount of immobilized sorbate molecules. Release of levothyroxine-Na with the highest values of R2 complies with the Higuchi (R2 = 0.968) in PBS for the CS/AG-11/LTH-Na-200 gel sample, with the Hixson-Crowell (R2 = 0.9156) and Korsmeyer-Peppas (R2 = 0.8594) kinetic models in the presence of elastase for the CS/AG-21-200, and best fitted to the Korsmeyer-Peppas (R2 > 0.9245) kinetic model for the CS/AG-51-200 gel in all media. In addition, a suspension of biopolymer hydrogel and its conjugate with levothyroxine in gastric medium was prepared and its acute and chronic toxicity was determined by injection (per os) method. It has been established that levothyroxine combined with a synthesized biopolymer belongs to the “practically non-toxic” group.

Fabrication of a pH-Responsive Magnetic Nanocarrier Based on Carboxymethyl Cellulose-Aminated Graphene Oxide for Loading and In-Vitro Release of Curcumin

In this study, a pH-responsive magnetic drug delivery system was prepared by cross-linking of Cofe2O4/graphene oxide to carboxymethyl cellulose (CMC) biopolymer with adipic acid dihydrazide (ADH) and then investigated for loading and release of a poorly water-soluble anti-cancer drug, curcumin (CUR). The CoFe2O4/GO-ADH-CMC bio-nanocomposite was characterized by FE–SEM/EDX, TEM, FT–IR, XRD, TGA, VSM, and zeta-potential techniques. The highest amount of drug loading was achieved as 23.7 mg g–1 at 323 K, pH 6.0, and 120 mg L–1 CUR concentration. The study of adsorption isotherms revealed that the Sips model was best fitted to the equilibrium data (R2 > 0.997 and RMSE < 0.48), which indicated the contribution of both chemisorption and physisorption in drug loading. Furthermore, the release profile of CUR from drug-loaded CoFe2O4/GO-ADH-CMC was studied in mimicking the endosomal (pH = 5.6) and physiological (pH = 7.4) conditions. After 24 h, the maximum cumulative releases were found to be 86 and 38% at pH = 5.6 and 7.4, respectively. Also, the Peppas-Sahlin kinetic model was followed for the release data. The MTT assay exhibited good biocompatibility of the CoFe2O4/GO-ADH-CMC. The results implied that CoFe2O4/GO-ADH-CMC magnetic bio-nanocomposite might be utilized as a potentially safe carrier with the continuous and slow release of CUR.Graphical Abstract

Nanogels loading 5-Fluorouracil in situ through thiol-ene click reaction and photopolymerization at 532 nm for its controlled release

Drug-loaded nanogels have attracted extensive research interest and shown great potential for many biomedical applications. A facile preparation method for drug-loaded nanogels is desirable to be developed. In this study, a range of nanogels were prepared by combining thiol-ene click reaction and photopolymerization at 532 nm for in situ loading 5-Fluorouracil (NG-S). The drug loading amount was improved by introducing mercaptosuccinic acid (MCA) to trigger thiol-ene click reaction. The drug loading capacity and swelling ratio characteristics of NG-S could be tuned by changing the proportion of PEGDA/MCA and the initial dose of drug. Especially, the drug release performance of the NG-S showed that 5-Fluorouracil presented the relatively excellent behavior of controlled release with a sustained release time up to 20 h in PBS (pH 7.4) at 37 °C. The fitting results of NG-S based on R2 were consistent with the First order, Weibull and Biexponential kinetic models.

Antibiotic loaded electrospun poly (lactic acid) nanofiber mats for drug delivery system

Active material-loaded nanofibers becoming more important, because of their applications in many areas such as wound healing, skin engineering, and drug release. This study was conducted to compare the release kinetics of three different antibiotics loaded on nanofibers in Phosphate-buffered saline (PBS) solution and their inhibition properties against bacteria. The three different commercial antibiotics; vancomycin (VAN), ceftriaxone (CFT), and cefpodoxime (CFD) were loaded into Polylactic acid (PLA) nanofibers via electrospinning process with different percentages; 5%, 7.5%, and 10% weight ratios of PLA. The SEM images of PLA/Antibiotic nanofibers and pure PLA nanofiber revealed an increase in diameters with the presence of antibiotics embedded in PLA nanofiber. The TGA analysis showed that the thermal degradation of CFD and VAN-loaded nanofibers were higher than neat PLA, while the thermal stability of CFT loaded nanofibers was the lowest. In the Tan Delta curves, the Tg temperatures of CFD, VAN, CFT loaded nanofibers and pure PLA nanofiber were determined as 54.56 °C, 54.57 °C, 53.86 °C, and 53.55 °C, respectively. As can be seen from the results, the variation of the glass transition temperatures supports the DSC data. Drug releasing behaviors of PLA/Antibiotic nanofibers were investigated by Ultraviolet–Visible Spectroscopy at 280, 242 and 230 nm wavelength for VAN, CFT, and CFD antibiotics, respectively. Drug-releasing amounts were gradually increased by increasing the drug loading amounts from 5% to 10%. PLA-VAN, PLA-CFT, and PLA-CFD nanofibers which contain 10% of drugs were delivered about 79%, 75%, and 29% of drugs linearly within nearly 380 h, 500 h, and 360 h, respectively. The formulations including CFT at different concentrations were found to be effective against Staphylococcus aureus and Escherichia coli in a dose-dependent manner. The formulations including CFD and VAN at different concentrations have also inhibited the growth of S. aureus.

Molecular dynamics simulations can predict the optimum drug loading amount in pectin hydrogels for controlled release

Determining an optimum drug concentration to modulate drug release from a flexible and dynamic system, such as hydrogels requires an extensive amount of experiments consuming time and money. Here, we conduct molecular dynamics (MD) simulations to predict an optimum drug concentration to load on low-methoxyl pectin hydrogels, which can maintain the structural integrity and achieve controlled drug release. Systems of low-methoxyl pectin hydrogel modeled as poly-galacturonic acid (PGAL) oligomers cross-linked with Ca2+ and procaine at different concentrations (0, 6, 30, 60, 90, 180 mg procaine/g hydrogel) are investigated. First, a series of 200 ns long all-atom MD simulations in explicit water with replicas are conducted reaching a total simulation time of 3.6 µs. We then assess our predictions with procaine release experiments from low-methoxyl pectin hydrogels, and calculation of storage G' and loss G'' moduli of hydrogel samples. Local and global motions of cross-linked PGAL oligomers from simulation trajectories are analyzed in detail to predict an optimum procaine concentration of 30 mg/g hydrogel. At this loading amount, polymer fluctuations are stabilized and initial monomer neighbors are maintained with a low average distance deviation of 1.5 Å so as to yield an intact hydrogel network. Results from MD simulations and experiments strongly agree. Pectin hydrogels loaded with 30 mg procaine /g have a low hydrogel degradation rate 0.001 g/min and a controlled in vitro drug release when compared to other samples, releasing all 30 mg of loaded procaine from 670 mg hydrogel in 24 h. Results indicate that drug release from the flexible host is mainly controlled by local and global motions of the polymer chains and non-bonded interactions between the system components. The computational approach taken here can be highly useful for similar polymer-based drug delivery systems.

Improvement of curcumin loading into a nanoporous functionalized poor hydrolytic stable metal-organic framework for high anticancer activity against human gastric cancer AGS cells

Two low water-stable nanoporous Zn-based Metal-Organic Frameworks (MOFs) with and without the NO2-functional group were synthesized by the reflux method and used to encapsulate curcumin (CCM). The characterization and application of these Zn-based MOFs (DMOF-1 and DMOF-1-NO2) have been studied by FT-IR, PXRD,1H NMR, N2 adsorption, SEM, UV-vis, and fluorescence microscopy methods. The amount of drug loading of DMOF-1 and DMOF-1-NO2 is 22.4 and 28.3 wt%, respectively. The drug loading results were also investigated by the computational simulation method. These kinds of MOFs have poor stability against water. This instability was used as a key to solving the problem of the low solubility of CCM as a model of hydrophobic cancer drug in a water-based medium. The obtained results confirmed that these poor hydrolytic MOFs could improve the solubility of CCM and enhance cytotoxicity against cancer cells (AGS) in comparison with free CCM. These results can prepare a new opportunity to increase the anticancer activity of hydrophobic drugs.

Preparation, characterization, and antibacterial activity of tigecycline-loaded, ultrasound-activated microbubbles

Central nervous system infectious disease caused by the multidrug-resistant Acinetobacter baumannii (AB) seriously threatens human life in clinic. Tigecycline has good sensitivity in killing AB, but due to its wide tissue distribution and blood-brain barrier, concentration in cerebrospinal fluid is low, therefore, the clinical effect is limited. Herein, we designed micro-bubbled tigecycline, aimed to enhance its anti-MDRAB effects under ultrasound. The lipid microbubbles with different ratios of lipids to drugs (a ratio of 10:1, 20:1, and 40:1) were prepared by the mechanical shaking method. The morphology, zeta potential and particle size of microbubbles were tested to screen out the much better formulation. Encapsulation efficiency and drug loading amount were determined by ultracentrifugation combined with high-performance liquid chromatography. Then the in vitro antibacterial activity against AB was conducted using the selected ultrasound-activated microbubble. Results showed the selected microbubbles with high encapsulation efficiency and good stability. The mechanical shaking method is feasible for preparation of drug-loaded and ultrasound-activated lipid microbubbles. Using 0.2 mg/mL microbubbles, combined with 1 MHz, 2.5 W/cm2 and 1 min of ultrasound exhibited a potent anit-AB in vitro. This study indicates that tigecycline treatment in form of ultrasound-activated microbubble is a promising strategy against AB infections.

Molecular Dynamics Prediction Verified by Experimental Evaluation of the Solubility of Different Drugs in Poly(decalactone) for the Fabrication of Polymeric Nanoemulsions

Nanoemulsions are a rapidly growing drug delivery technology capable of increasing a drug's aqueous solubility and stability. A novel oil‐in‐water nanoemulsion using a polymer, poly(decalactone) (PDL), instead of a conventional oil was recently reported. The amount of drug loading in a polymer‐based formulation is mainly governed by the drug's solubility in the polymer. Thus, herein the power of molecular dynamics simulations (MDS) for the calculation of the Hildebrand solubility parameter to predict PDL–drug miscibility is utilized. The MDS results are subsequently verified by formulating a PDL nanoemulsion with a dispersed droplet size of less than 200 nm by using a block copolymer of PDL (mPEG‐b‐PDL) as a surfactant, with seven different hydrophobic drug molecules. The MDS results are consistent with the experimental findings in terms of increment in the aqueous solubilities of the drugs in PDL nanoemulsion, where celecoxib demonstrated the highest while methotrexate exhibited the lowest solubility increment. Consequently, the reported MDS method can be utilized to predict a drug's solubility/miscibility in PDL to estimate the level of drug loading. The MDS facilitated screening of drugs could consequently emerge as an efficient approach in designing PDL nanoemulsions stabilized by mPEG‐b‐PDL or other similar systems.

An In Vitro Comparative Study of Three Drug-Eluting Beads Loaded with Raltitrexed.

Background: This study investigated the raltitrexed loading method, compatible stability with contrast agent, release profiles, and morphological properties of CalliSpheres, DC Bead, and HepaSphere. Materials and Methods: The amounts of raltitrexed added, loading medium, loading condition, and drug concentrations were investigated as factors influencing drug loading efficiency. Compatible stability with iopamidol was tested. Release profiles were accessed by a flowthrough apparatus system. Morphological properties were evaluated by a scanning electron microscope (SEM). Diameters were measured by a laser diffraction particle size analyzer. Results: With the optimized method, the amount of raltitrexed loading to a marketed drug-eluting beads (DEBs) package was 2.67 mg for CalliSpheres, 2.34 mg for DC Bead, and 3.19 mg for HepaSphere. For all three DEBs, the drug leak rate was >50% within 2 h after mixing with iopamidol, and the time to reach 75% of the release plateau was within 10 min. Diameters increased after drug loading. Drug crystals were observed on the surface of DEBs in SEM. Conclusions: The amount of drug loading could meet clinical requirements by the optimized method. All three raltitrexed-loaded DEBs showed poor compatible stability with iopamidol, as well as rapid drug release performance, which should be noticed in clinical practice.

Monte Carlo and Molecular Dynamics Simulations suggest controlled release of corticosteroids from mesoporous host MIL-101 (Cr)

ABSTRACT Controlled release of corticosteroids may lead to higher bioavailability of the drugs and a dosage control. Here, we investigate the suitability of the framework MIL-101 (Cr) as a drug carrier for a controlled release of five corticosteroids with different therapeutic potencies, namely Desoximethasone and Clobetasol Propionate (strong), Methylprednisolone and Triamcinolone Acetonide (medium), Hydrocortisone Valerate (weak). First, we employ Grand Canonical Monte Carlo (GCMC) simulations and calculate the storage capacity of the host to be around 1000 mg drug/g MIL-101 (Cr). Then, Canonical MC simulations are performed, which cover different drug loading amounts from high (400 mg/g) to low (50 mg/g). Results suggest a multi-step drug release trend controlled by the interplay between drug–drug and drug-framework interactions at the atomistic level. Then, all-atom molecular dynamics simulations for 50 mg/g loading are used to monitor the evolution of the interactions between the drug molecules and the framework. All results indicate that MIL-101 (Cr) is a highly promising corticosteroid carrier that may also prevent unintentional misuse by patients.

Black Phosphorus Nanosheet Encapsulated by Zeolitic Imidazole Framework-8 for Tumor Multimodal Treatments.

Black phosphorus (BP) nanosheet is easily oxidized by oxygen and water under ambient environment, thus, reliable BP passivation techniques for biomedical applications is urgently needed. A simple and applicable passivation strategy for biomedical applications was established by encapsulating BP nanosheet into zeolitic imidazole framework-8 (ZIF-8). The resulted BP nanosheet in ZIF-8 (BP@ZIF-8) shows not only satisfied chemical stability in both water and phosphate buffered saline (PBS), but also excellent biocompatibility. Notably, BP nanosheet endows the prepared BP@ZIF-8 with prominent photothermal conversion efficiency (31.90%). Besides passivation BP, ZIF-8 provides the BP@ZIF-8 with high drug loading amount (1353.3 mg g-1). Moreover, the loaded drug can be controlled release by pH stimuli. Both in vitro and in vivo researches verified the resulted BP@ZIF-8 an ideal candidate for tumor multimodal treatments.

Three months extended-release microspheres prepared by multi-microchannel microfluidics in beagle dog models

To evaluate in vivo drug release profiles in beagle dogs, finasteride-loaded PLGA microspheres were prepared using a novel method of IVL-PPF Microsphere® microfluidic device. Briefly, the dispersed phase (PLGA and finasteride in dichloromethane) was mixed with the continuous phase (0.25% w/v PVA aqueous solution) in the parallelized microchannels. After lyophilization, the diameter of the microspheres was around 40 μm (PLGA 7502A or 5002A) and around 30 µm (PLGA/PLA02A mixture). Their CV and span values suggested a narrow size distribution in repeated batch preparations. The in vivo drug release from the PLGA microspheres exhibited three substantial phases: an initial burst, a moderate release, and then a plateau. The microspheres based on PLGA 7502A (75:25 co-polymer) demonstrated extended drug release for around 1 month with a minimized initial burst release compared to PLGA 5002A (50:50 co-polymer). Moreover, the in vivo drug release profile in beagle dogs was proportionally related to the amount of drug loading. Furthermore, the addition of PLA02A into the fabrication of the microsphere synergistically extended the drug release up to 3 months. These results demonstrated the value of this method to achieve uniform microspheres and extend the drug release properties with interpretative in vivo PK profiles.

Swellable microneedles based transdermal drug delivery: Mathematical model development and numerical experiments

Recently, swellable microneedles (SMNs) have gained significant interest due to their potential applications in transdermal drug delivery (TDD). SMNs swell by absorbing interstitial fluid in the skin, and they facilitate drug transport into the skin without polymer dissolution. To establish the SMNs for practical usages, one requires an accurate understanding of the drug transport mechanisms from these MNs that would allow both controlled TDD as well as optimisation of the MN geometries. In addressing this issue, a mathematical model is formulated which incorporates the key parameters defining the skin properties and physicochemical properties of the MNs, such as the polymer swelling capacity, mechanical deformation, amount of drug loading, and penetration depth in the skin. Numerical simulations are performed using well-defined MN parameters which represent the MN constituent and drug, namely, polyvinyl alcohol and insulin, in this study. The proposed mathematical model predicts that insulin diffuses into the blood to reach a maximum concentration of 11.72 ng/ml in 1.5 h, and ~95% insulin is eliminated from the blood within 11 h. The rate of insulin diffusion to blood increases with an increase in MN swelling. However, not much difference is observed in the insulin profiles when MNs swell more than two times their mass as the skin tends to displace the MN out of the skin, as it increases the length of the diffusion pathway for the drug in the skin layers. The depth of MN penetration affects the overall insulin delivery, with insulin getting eliminated from the body in 8 h when MN is fully inserted into the skin. The rate of change of blood concentration of insulin is found to increase and decrease non-linearly with time for the cases studied in this paper. The developed model provides a platform for optimization of SMNs for the controlled delivery of different drug molecules.

Triformyl cholic acid and folic acid functionalized magnetic graphene oxide nanocomposites: Multiple-targeted dual-modal synergistic chemotherapy/photothermal therapy for liver cancer

Photo-chemotherapy (PCT) reveals great potential in hepatocellular carcinoma (HCC) treatment, therefore the construct of smart PCT nano-agents with high photothermal conversion efficiency and accurate drug delivery is of great significant. Herein, a novel hybrid nanomaterial MGO-TCA-FA has been designed and constructed by grafting the triformyl cholic acid (TCA) and folic acid (FA) on the surface of Fe3O4 modified graphene oxide (MGO). The doxorubicin hydrochloride (DOX) as a model drug could be effectively loaded on the MGO-TCA-FA via hydrogen bonding and π-π stacking (the drug loading amount was 1040 mg/g). The formed MGO-TCA-FA@DOX has been developed to be an effective PCT nanoplatform with the advantages of multiple-targeted drug delivery, near-infrared light (NIR) and pH triggered drug release, and photothermal conversion efficiency. In vitro experiments showed that compared with other cancer cells and normal liver cells, MGO-TCA-FA@DOX could specifically target liver cancer cells and presented significant killing ability to liver cancer cells. More importantly, in vivo experiments indicated that PCT synergistic therapy (MGO-TCA-FA@DOX) revealed the best tumor inhibition (the tumor inhibition rate was about 85%) compared with chemotherapy and photothermal therapy alone. Thus, this study supplied a viable multiple-targeted PCT nano-agent for chemo-photothermal combination therapy of liver cancer.

PEG Modificated Bubble‐Like Carbon Spherical‐W18O49 Using for In Vitro Chemotherapy‐Photothermal Synergistic Reverse Cancer Cells

AbstractIn this study, a chemotherapy‐photothermal synergistic anti‐tumor system is constructed. Both W18O49@R‐C and PEG‐W18O49@R‐C synthesized by hydrothermal method show the potential of photothermal therapy (PTT). The structure of reflux‐carbon is bubble‐like spherical and W18O49@R‐C obtained by hydrothermal synthesis will cause bubble collapse due to the formation of crystal W18O49; thus, the particle size decreases sharply. Furthermore, the photothermal stability of PEG‐W18O49@R‐C is higher than that of W18O49@R‐C, and ζ‐potential measurement indicates that PEG‐W18O49@R‐C has excellent dispersion characteristics. The test of drug loading and drug release performance show that PEG‐modified W18O49@R‐C has superior performance on drug loading amount and release capacity. In the synergistic anti‐tumor process, the cancer cell viability after co‐incubating with PEG‐W18O49@R‐C+DOX.HCl (with 808nm) is only 16.6%. These results indicate that PEG‐W18O49@R‐C has potential in the treatment of cancer by a combination of PTT and chemotherapy.

Chitosan coated biocompatible zeolitic imidazolate framework ZIF-90 for targeted delivery of anticancer drug methotrexate

In this work, using zeolitic imidazolate framework (ZIF) as carrier, a new biocompatible anti-cancer drug delivery system CS@MTX@ZIF-90 (CMZ) was efficiently synthesized by one-pot method. Methotrexate (MTX), an anticancer drug as folic acid analogue was loaded into ZIF-90 through Schiff base reaction between amino group in MTX and aldehyde group of imidazole-2-carboxaldehyde ligand with drug loading amount about 250 ​mg/g. As a pH-sensitive biomaterial, chitosan (CS) was modificated by the outer layer of the particles to improve the pH responsiveness of the composite CMZ during the drug release process. By releasing a large amount of MTX under acidic conditions (the pH environment around tumor cells), and releasing a substantially lower amount of MTX at a normal environment, CMZ exhibited a pH-responsive and target-selective behavior. In addition, in vitro cytotoxicity and anticancer activity results showed that CMZ can inhibit the growth of liver cancer HepG2 cells, prostate cancer DU145 ​cells and gastric cancer SGC7901 ​cells, with only negligible toxicity to normal EC304 ​cells. Based upon the results of corresponding experiments, CMZ exhibited high MTX drug loading, cancer-targeted release and good biocompatibility, which can be used as a good candidate for anticancer drug delivery system.

Construction and evaluation of red blood cells-based drug delivery system for chemo-photothermal therapy

In this study, a novel tumor-targeting drug delivery system (DDS) based on red blood cells (RBCs) were fabricated for combinational chemo-phototherapy against cancer. Cyclic peptide (cRGD) and indocyanine green (ICG) were applied to the surface of RBCs to increase the targeting and photothermal effect, respectively. Doxorubicin (DOX) as a model drug was loaded into RBCs by the hypotonic dialysis method. A series of tests have been carried out to evaluate the RBCs-based DDS and these tasks include physicochemical properties, cellular uptake, targeting ability, and combination therapeutic efficiency. As a result, the DOX was successfully loaded into RBCs and the drug loading amount was 0.84 ± 0.09 mg/mL. There was no significant change of particle size after surface modification of RBCs. The RBCs-based DDS could target to the surface of cancer cells, which delivery DOX to the lesions efficiently and accurately. Meanwhile, due to the combined treatment effect, the RBCs-based DDS can effectively inhibit tumor growth. The RBCs-based DDS constructed in this research may have promising applications in cancer therapy due to their highly synergistic efficient therapy and to investigate its possibility for tumor therapy.

Preparation and characterization of gelatin base cross-linking aerogel and nanoclay aerogel for diltiazem drug delivery

In this investigation, we decided to prepare efficient aerogel for loading and releasing drug in vitro situation. Here we introduced the synthesis of gelatin-based cross-linking poly vinyl acetate/acrylic acid aerogel and nanoclay aerogel, which synthesized by free radical condition and called gelatin-g-VA–AA (A) and gelating-VA–AA/MMT (B), respectively, and they were used them for drug delivery of diltiazem. The synthesized aerogels were completely identified by FTIR, TGA, DTG, SEM, TEM, XRD that showed nanocomposites size with about 40–70 nm, highly uniform porous surface and with high temperature stability. In addition, drug delivery activities of aerogels were tested in saline solution, temperature, the percentage of nanoclay and time effect. Moreover, pH sensitivity of aerogels was investigated for characterization of drug loading and drug releasing amounts at different pHs, distilled water and buffers to determine the best condition for each situation which results illustrated the universal buffer at pH 5 and 7 for drug loading and pH 7 and 10 for drug releasing had the least interaction with aerogels and nano-aerogel, respectively.

Preparation of Multifunctional Drug‐loaded Microcapsules with Core‐shell Three‐dimensional Network Structure and their Application in Colon Targeted Release

AbstractSome special oral drugs may cause adverse reactions and degrade in the stomach; therefore, it is necessary to develop a new generation of multifunctional drug delivery carries to deal with such issues. Herein, by polyelectrolyte composite method using KGM and CS as raw material, CKGM/CS/TPP/5‐ASA microcapsules are prepared using 5‐ASA as model drug, and then coated with an acid‐resistant polyacrylic acid polymer layer. The size of CKGM/CS/TPP/5‐ASA microcapsules is relatively uniform, with average particle size 1.78 ± 0.02 mm. The inner part of microcapsules has a core‐shell three‐dimensional network structure, and the 5‐ASA embedded in the network is in its crystal form. The microcapsules exhibited good encapsulate properties, with 495.5 µg mg−1 drug loading amount and 82.3% encapsulation efficiency under optimized conditions. The in vitro release properties of microcapsules are also studied, and results showed that the drug is released little in Simulated Gastric Fluid solution (pH 1.2) but fully released in Simulated Colonic Fluid or Phosphate Buffered Solution (pH 7.0), and the release rate is higher in SCF solution, indicating that β‐mannanase could facilitate release. All these results indicated that CKGM/CS/TPP microcapsules have good pH‐controlled release, enzymatic release, and sustained release properties, hence they are promising multifunctional colon‐targeted release carriers.