Drug Carrier Material Research Articles

Evaluation of the therapeutic effect of mitomycin-loaded hydrogel in inhibiting tumor-cell proliferation and invasion in pancreatic cancer

Pancreatic cancer is a common tumor of the digestive system with a high degree of malignancy and poor prognosis. Its incidence has significantly increased worldwide in recent years. Currently, approximately 90% of patients cannot be treated surgically. Thus, drug therapy plays an important role in pancreatic cancer treatment. In this study, hydrogels loaded with mitomycin were prepared from hyaluronic acid and carboxymethyl chitosan, which have excellent biocompatibility. SEM results showed that the hydrogels had a three-dimensional interoperable porous structure, and CCK-8 results showed that hydrogels loaded with mitomycin significantly reduced cancer-cell proliferation. The hydrogels also reduced the migration of cancer cells in a dose-dependent manner, indicating their potential use as a drug-carrier material for pancreatic cancer treatment.

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System.

Drug delivery system (DDS) realizes the drug delivery process through the drug carrier. As an important part of DDS, the selection of the drug carrier material is extremely critical, which requires the carrier material to possess excellent biocompatibility and targeting and not affect the pharmacological action of the drug. As one of the endogenous extracellular vesicles, exosomes are 30-100 nm in diameter, which are considered a new generation of a natural nanoscale delivery system. Exosomes secreted by different types of cells carry signaling molecules (such as proteins and nucleic acid) playing an important role in cell behaviors. Owing to their ability to specialize in intercellular communication, exosomes provide a distinctive method to deliver therapeutic drugs to target cells. In this concept, exosomes as the natural liposomes carry endogenous biomolecules, have excellent biocompatibility, and could be loaded with cargo both in vivo and in vitro. In addition, modifications by genetic and/or chemical engineering to part of the exosome surface or complement the desired natural effect may enhance the targeting with drug loading capability. Notably, exosomes weakly react with serum proteins prolonging cargo half-life. Overall, exosomes as natural carriers integrate the superiority of synthetic nanocarriers and cellular communication while precluding their limitations, which provides novel and reliable methods for drug delivery and treatment. Our review focuses on the therapeutic potentials and clinical values of exosomes as a carrier of drug delivery system in multiple diseases, including cancer, nervous, immune, and skeletal system diseases.

Polycaprolactone/epoxide-functionalized silica composite microparticles for long-term controlled release of trans-chalcone

Abstract In this study, controlled release of trans-chalcone was achieved by using a polycaprolactone-based hybrid system as the drug carrier material. Encapsulation efficiency was obtained in the range of 70–75% for various formulations and in vitro release studies, conducted at 37 °C and pH 7.4, revealed slow profile reaching 60% cumulative release. As interpreted from kinetic modelling, drug release was controlled mainly by Fickian diffusion; polymer erosion did not contribute to the TC release. Difference in drug loading efficiencies of the hybrid and neat PCL microparticles was observed such that PCL microparticles had lower loading efficiency than the hybrid microparticles whereas the release profiles were similar. pH of the release medium had affected release profiles; acidic medium enhanced drug release. Characterization of the microparticles were realized by FT-IR, TGA, DSC, SEM and WCA which revealed key properties such as molecular dispersion state and hydrophilicity. With the results obtained, we concluded that our hybrid system has a significant potential for long term release of trans-chalcone.

Therapeutic Effect and Mechanism of Norfloxacin-Loaded Poly(lactic-co-glycolic acid) Microspheres on Urinary System Infections

Urinary system infections are one of the most common infectious diseases in clinical practice. Patients prone to secondary infections need to take antibacterial drugs for a long time. Therefore, the development of a drug-carrying material with long-term antimicrobial activity is an urgent problem for urology-allied medical materials science. In this study, PLGA microspheres with excellent biocompatibility were prepared using PLGA as the carrier and norfloxacin as the drug model. The size of norfloxacin/PLGA microspheres was mainly concentrated in 2.19–8.08 μm, exhibiting a small surface area and good slow-release effect in vitro. Biological experiments showed that PLGA microspheres can reduce the inflammatory cytokine content in plasma, have a good bactericidal effect, and are expected to be used as drug carrier materials for urinary system infections.

Polyelectrolyte Chondroitin Sulfate Microgels as a Carrier Material for Rosmarinic Acid and Their Antioxidant Ability.

Polyelectrolyte microgels derived from natural sources such as chondroitin sulfate (CS) possess considerable interest as therapeutic carriers because of their ionic nature and controllable degradation capability in line with the extent of the used crosslinker for long-term drug delivery applications. In this study, chemically crosslinked CS microgels were synthesized in a single step and treated with an ammonia solution to attain polyelectrolyte CS−[NH4]+ microgels via a cation exchange reaction. The spherical and non-porous CS microgels were injectable and in the size range of a few hundred nanometers to tens of micrometers. The average size distribution of the CS microgels and their polyelectrolyte forms were not significantly affected by medium pH. It was determined that the −34 ± 4 mV zeta potential of the CS microgels was changed to −23 ± 3 mV for CS− [NH4]+ microgels with pH 7 medium. No important toxicity was determined on L929 fibroblast cells, with 76 ± 1% viability in the presence of 1000 μg/mL concentration of CS−[NH4]+ microgels. Furthermore, these microgels were used as a drug carrier material for rosmarinic acid (RA) active agent. The RA-loading capacity was about 2.5-fold increased for CS−[R]+ microgels with 32.4 ± 5.1 μg/mg RA loading, and 23% of the loaded RA was sustainably release for a long-term period within 150 h in comparison to CS microgels. Moreover, RA-loaded CS−[R]+ microgels exhibited great antioxidant activity, with 0.45 ± 0.02 μmol/g Trolox equivalent antioxidant capacity in comparison to no antioxidant properties for bare CS particles.

Optimize PLA/EVA Polymers Blend Compositional Coating for Next Generation Biodegradable Drug-Eluting Stents.

In this research work, polymer blends of poly-lactic acid (PLA)/ethylene vinyl acetate (EVA) were prepared as the drug carrier materials for a bi-layer drug-loaded coating film for coronary stents. Different optimum compositions of blends were prepared by using an intense mixer. Then, the blends were hot-pressed and later cold-pressed to prepare for films of different thickness. The changes in weight, surface analysis and biodegradability with increasing time were studied using Scanning electron microscopy (SEM), weight loss and biodegradability tests. The mechanical and thermal properties of drug-loaded films were studied through universal testing machine (UTM) and thermo-gravimetric analysis (TGA). The effects of PLA, EVA and drug contents on in-vitro drug contents were investigated through the Ultraviolet-Visible Spectroscopy (UV-VIS) chemical analysis technique. The results obtained clearly showed that the addition of PLA promoted the unleashing of the drug whereas the addition of EVA nearly did not have the same affect. The mechanical properties of these various films can be tuned by adjusting the contents of blend parts. The factors affecting the unleashing of the drug became a serious matter of concern in evaluating the performance of bio-resorbable drug eluting stents. As a result, today’s chemical blends may be useful drug carrier materials for drug-loaded tube coatings capable delivering purgative drug in an incredibly tunable and regulated manner.

Formation and growth mechanism of Strontium hydroxyapatite cellular crystal sphere

Strontium hydroxyapatites (SrHAps) find widespread applications in bone tissue engineering and drug carrier material for bone disease treatment because of biocompatibility. Morphology controlled preparation of SrHAps and understanding of the synthesis mechanism are critical to rationalize design hierarchically structured SrHAps and expand their applications. Herein, SrHAp cellular crystal spheres have been synthesized by using (NH4)3C6H5O7– induced (citrate-induced) homogeneous precipitation method under ambient pressure. Morphology characterization has shown that the as-obtained SrHAp is the secondary particle, while the spherical structure constituted the primary cellular crystal. Driving force of Sr2+ concentration gradient in phase transition has been analyzed to explain the synthesis mechanism of unique hierarchically structured SrHAp cellular crystals. The formation of SrHAp cellular crystal spheres can be attributed to the strong coordination within C6H5O73– and Sr2+ to form a 3D grid-like structure. This research has been able to overcome the longstanding limitations of traditional synthesis methods to establish the efficient route for synthesizing SrHAp with special morphology and predictable and controllable hierarchically structured SrHAp.

Recent Progress in Red Blood Cells-Derived Particles as Novel Bioinspired Drug Delivery Systems: Challenges and Strategies for Clinical Translation.

Red Blood Cells (RBCs)-derived particles are an emerging group of novel drug delivery systems. The natural attributes of RBCs make them potential candidates for use as a drug carrier or nanoparticle camouflaging material as they are innately biocompatible. RBCs have been studied for multiple decades in drug delivery applications but their evolution in the clinical arena are considerably slower. They have been garnering attention for the unique capability of conserving their membrane proteins post fabrication that help them to stay non-immunogenic in the biological environment prolonging their circulation time and improving therapeutic efficiency. In this review, we discuss about the synthesis, significance, and various biomedical applications of the above-mentioned classes of engineered RBCs. This article is focused on the current state of clinical translation and the analysis of the hindrances associated with the transition from lab to clinic applications.

Preparation of porous starch from native starch by using fungal amylase and evaluation of its adsorption property on natural pharmacodynamic compounds

AbstractDue to the reliable safety of starch, it has a wide range of applications in pharmaceutical fields and food sectors. Enzymatic preparation of porous starch can better maintain the properties of starch and expand its applications, which indicates that the research on starch is worthwhile. According to the enzymatic hydrolysis ratio and the morphology of starch particles, the technological method was determined by using unpretreated corn starch as raw material and the fungal amylase as hydrolysis amylase. Then the technological conditions for preparing corn porous starch through enzymatic hydrolysis were optimized by single factor experiment. The morphology of porous starch was obtained via scanning electron microscopy (SEM). The infrared spectrum (FTIR) showed that the porous starch had a same molecular structure compared with native starch. X‐ray diffraction (XRD) displayed that the crystal structure of porous starch was quite consistent with the native starch. The study on adsorption properties of porous starch for natural pharmacodynamic compounds genistein exhibited that the adsorption behaviors of porous starch were found to conform well to the Freundlich model and the pseudo‐first‐order model. Besides, the release assay demonstrated that the genistein which was incorporated into porous starch possessed superior sustained release effect. The porous starch obtained by enzymatic hydrolysis had ideal adsorption properties for natural pharmacodynamic compounds and is valuable as a drug carrier material.

High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury

Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8–63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 μg) within the limited administration volume (10 μL) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.

Study of mordenite natural zeolite type modified by Cu(II) cation as an oral safe drug carrier for ibuprofen and meloxicam

This research focused on the purification of mordenite (Mor) from the natural zeolite. Mor was then modified with Cu(II) to produce a new oral safe drug delivery material Cu(II)-Mor based on natural zeolite. Drug loading testing on Cu(II)-Mor used ibuprofen and meloxicam as drug models. The drug carrier and loading materials were characterized by using FTIR, XRD and FESEM-EDS. To use Cu(II)-Mor material as a drug carrier, in addition to the drug loading capacity factor, other factors such as drug release and zeta potential and cytotoxicity of drug delivery material were also investigated. The release of meloxicam from Cu(II)-Mor experienced the highest release at 1200 min in pH 7 with a dissolution percentage of 93.17%. The release of Ibuprofen from Cu(II)-Mor occurred at 1200 min in pH 7 with a dissolution percentage of 90.98 %. All release Ibuprofen and meloxicam were studied using six kinetics modeling: zero-order, first-order, Peppas-Sahlin, Higuchi, Hixson-Crowell and Korsmeyer-Peppas models. Based on kinetics modeling, ibuprofen and meloxicam release from Cu(II)-Mor followed Peppas–Sahlin model, indicating that Fickian diffusion and Case II relaxations dominate the drug transport mechanism from mordenite. The results showed that this drug carrier material has good cytocompatibility, drug loading and drug release. The results of the zeta potential test also show that the drug carrier material has high stability in the dispersion system. Overall, Cu(II)-Mor can be used as an oral safe drug material.

Synthesis of new type temperature and pH sensitive hydrogels using drug-based p-(methacryloyloxy)acetanilide monomer and their usage as controlled drug carrier material

In our study, as a functional monomer, p-(methacryloyloxy)acetanilide (MOAA) was synthesized and utility in hydrogel systems with various commercial monomers after the structural characterization was analyzed. In terms of temperature sensitivity and suitability for use in biological applications, N-isopropyl acrylamide (NIPAm) monomer and pH-sensitive acrylic acid (AAc) monomer were chosen among the commercial monomers. To the best of our knowledge, p(N-isopropyl acrylamide-co-p-(p-methacryloyloxy)acetanilide) (GEL 5) and p(N-isopropyl acrylamide-co-acrylic acid-co-p-(p-methacryloyloxy)acetanilide) (GEL 8) were synthesized in the form of a film with the free radical polymerization technique for first time in the literature. The structural characterizations and surface morphologies of the hydrogels p(NIPAm) (GEL 1), p(NIPAm-co-MOAA) (GEL 5), and p(NIPAm-co-AAc-co-MOAA) (GEL 8) were investigated by using the techniques of FTIR spectroscopy and scanning electron microscope (SEM). Moreover, the thermal resistance of all three hydrogels was brightened by the thermal gravimetric analysis (TGA). Swelling behaviors in different environments of the MOAA-based hydrogels, prepared as pH and temperature-sensitive, were examined, and biomedical applications are occurred by the investigation of the usability as a controlled drug delivery material. For this purpose, sodium diclofenac (NaDc) drug, used in pain and inflammation treatment, was chosen. In vitro release of NaDc from the drug-loaded hydrogel was examined in pH 5.5 (PBS) and pH 7.4 (PBS) media. Korsmeyer-Peppas model was used in defining the drug release mechanism.

Preparation and Investigation of Antibacterial Activities of Ciprofloxacin Imprinted p(HEMAH) Cryogels

Staphylococcus aureus, Enterococcus faecalis and Escherichia coli are the common causes of wound infections. For the treatment of these infections, ciprofloxacin can be recommended as a broad-spectrum antibiotic that acts on both Gram-negative and Gram-positive microorganisms. Besides, antimicrobial agents could be integrated into polymeric materials. Cryogels, one of these polymeric materials, are spongy polymers showing high macroporosity. In addition to their attractive usage as affinity support materials and scaffolds, they also appear as drug carrier materials in recent years. Molecular imprinting method is a recognition technique prepared by forming a polymeric network around the template. Although this method has been used in purification and separation processes for more than thirty years, it has gained great interest as a new approach that provides an advantage in drug release studies in terms of high drug loading capacity and long-term release.
 In this study, ciprofloxacin (CIP) imprinted 2-Hydroxyethyl methacrylate (HEMA) based N-methacryloyl-(L)-histidine methyl ester (MAH) containing [CIP-p(HEMAH)] cryogels was prepared and characterized. CIP releasing experiments were performed, and then, antimicrobial activities of CIP p(HEMAH) cryogels were examined against S. aureus, E. faecalis and E. coli. It can be concluded that CIP-p(HEMAH) cryogels could be proposed as promising polymeric materials for wound healing applications.

Delivery process and effective design of vectors for cancer therapy.

In recent years, the efficacy of nano-drugs has not been significantly better than that of the drugs themselves, mainly because nano-drugs enter the tumor vasculature, stay near the blood vessels, and cannot enter the tumor tissues or tumor cells to complete the drug delivery process. Although intratumor injection can significantly decrease this risk, the side effects are strong. The advent of drug delivery carrier materials offers an opportunity to avoid the side effects of systemic drug delivery and the damage caused by tumor resection, holding great promise for the future of cancer therapy. Here, we systematically review recent research advances in the classification of drug delivery carrier materials and the delivery process in drug delivery systems. This review is divided into several main sections, first, we summarize the classification of tumor drug carrier materials, including drug delivery vectors and gene delivery vectors, etc., which are introduced in detail, respectively. Then we describe the carrier materials to deliver the drug cascade and the transition pathways for drug delivery, including stabilization transitions, charge inversions, and size changes. Finally, we discuss the current design strategies and research progress of drug vectors and provide a summary and outlook. This review aims to summarize different drug delivery vehicles and delivery processes to provide ideas for effective cancer therapy.

How Does Fluid Flow Influence Drug Release from Drug Filled Implants?

Drug-filled implants (DFIs) have emerged as an innovative approach to control the delivery of drugs. These devices contain the drug within the structure of the implant itself and avoid the need to include additional drug carrier materials such as a polymers, which are often associated with inflammation and delayed healing/tissue regeneration at the implant site. One common feature of in vitro experiments to generate drug release profiles is stirring or agitation of the release medium. However, the influence of the resulting fluid flow on the rate of drug release from DFIs has yet to be quantified. In this paper we consider two DFIs, which although similar in shape and size, employ different strategies to control the release of drug: a porous pin with pores on the order of μm and a pin drilled with orifices of the order of mm. We develop a multiphysics mathematical model of drug release from these DFIs, subject to fluid flow induced through stirring and show that fluid flow greatly influences the drug release profile for the orifice pin, but that the porous pin drug release profile is relatively insensitive to flow. We demonstrate that drug release from the porous pin may adequately be described through a simplified radial 1D dissolution-diffusion model, while a 3D dissolution-advection-diffusion model is required to describe drug release from the orifice pin. A sensitivity analysis reveals that that the balance of reaction-advection-diffusion in terms of key nondimensional numbers governs the overall drug release. Our findings potentially have important implications in terms of devising the most relevant experimental protocol for quantifying drug release from DFIs.

Preparation of ordered porous Mg-HA and drug sustained-release performance

ABSTRACT Hydroxyapatite (HA) is an effective drug carrier material. The addition of Mg can improve the drug release and degradation properties of HA. In this paper, HA was designed into an ordered porous structure and Mg was added to enhance amoxicillin sustained-release performance. The ordered porous HA with various Mg addition was prepared by the template method. Effects of Mg addition on the morphology and phase of the ordered porous HA and the sustained-release performance of amoxicillin were investigated. The results showed that the ordered porous morphology did not change significantly with the increase of Mg addition. When the addition of Mg was more than 3 mol%, the main crystalline phase of HA changed to β-TCP, which helped to improve the degradation performance. The amoxicillin loading of the ordered porous 1 mol% Mg-HA was about 85.9 mg/g, which was higher than that of the ordered porous pure HA. In the first 5 h of the amoxicillin release experiment, the cumulative release rate of amoxicillin on the ordered porous HA contained magnesium (Mg-HA) was less than 50%, indicating that the material had good sustained-release performance of amoxicillin. The ordered porous Mg-HA has great application potential in quantitative drug delivery systems.

Investigation of morphology, micelle properties, drug encapsulation and release behavior of self-assembled PEG-PLA-PEG block copolymers: A coarse-grained molecular simulations study

Targeted drug delivery has become one of the key fields of personalized medicine. Developing candidate drug delivery agents requires a thorough understanding of the drug carrier materials by means of structure, drug encapsulation and release properties. To this aim, coarse-grained DPD simulations are employed to study the morphology, drug encapsulation and release of a particular amphiphilic block copolymer system. Extent of the drug encapsulation and release are observed to be mainly affected from copolymer concentration in the mixture. Mean aggregation number and average micelle volume are observed to increase as drug is encapsulated in the micelles. In addition, the shape of micelles is characterized as mainly spherical. It is observed that the drug release follows a pseudo-Fickian diffusion model and can be represented by the Korsmeyer-Peppas model. Furthermore, the diffusion rate of the drug molecules is observed to increase mainly in the release-phase. Our simulations can be viewed as a computational attempt to model the drug encapsulation and release by mimicking real experimental conditions, while yielding results on the structure and dynamics of the polymeric carrier. The results can be anticipated to find applications in understanding and controlling the parameters to design candidate drug delivery micelles at the molecular level.

Preparation of organic-modified magadiite–magnetic nanocomposite particles as an effective nanohybrid drug carrier material for cancer treatment and its properties of sustained release mechanism by Korsmeyer–Peppas kinetic model

Preparation of organic-modified magadiite–magnetic nanocomposite particles as an effective nanohybrid drug carrier material for cancer treatment and its properties of sustained release mechanism by Korsmeyer–Peppas kinetic model

Synthesis and characterization of biodegradable and antioxidant phosphazene-tannic acid nanospheres and their utilization as drug carrier material

In this study, hexachlorocyclotriphosphazene (HCCP) and tannic acid (TA) were used at different stoichiometric ratios to synthesize cyclomatrix-type polymeric materials with different surface features and dimensions. Using different reactive ratios, the structure and surface functional groups of the synthesized polymeric particles were explained using Fourier-Transform Infrared Spectroscopic (FTIR), Scanning Electron Microscope (SEM), Energy-dispersive X-ray spectroscopy (EDX), X-ray Photoelectron Spectroscopy (XPS) and Thermogravimetric (TG) analysis techniques. With morphologically fully spherical structure and mean 234.82 ± 49.37 nm dimensions, Phz-TA (4:1) nanospheres were researched for in vitro biodegradability, antioxidant features, and usability as a drug release system. In vitro biodegradability of Phz-TA (4:1) nanospheres was investigated at pH = 7.0 and pH = 1.2. Determined to degrade in 8–10 h at these pH values, nanospheres were used for releasing of Rhodamine 6G as a model drug. Due to the rich phenolic structure of the contained tannic acid units, nanospheres were determined to simultaneously have antioxidant features. Thus, this study determined that Phz-TA nanospheres with in vitro biodegradability and antioxidant features are promising polymeric materials for use as a potential drug-carrier in the future.

PH-responsive injectable polysaccharide hydrogels with self-healing, enhanced mechanical properties based on POSS

Injectable polysaccharide-based hydrogels are widely employed as drug delivery and tissue engineering materials due to the promising biocompatibility and biodegradability, while the mechanical property of polysaccharide hydrogels still requires to be enhanced much for further applications. In the present work, a family of injectable nanocomposite hydrogels were prepared for the first time through the Schiff base reaction between cationic octa (γ-chloroammoniumpropyl) silsesquioxane (OCAPS), chitosan (CS), and oxidized hydroxypropyl cellulose (HPC). It was found that OCAPS dispersed well in the hydrogels and inhibited the crystallization of CS and HPC, and the resulted nanocomposite hydrogels response pH values by reversible sol-gel transitions, namely as the pH value was less than 4.2, the hydrogels were low viscous solutions; while gelled again in mild and basic conditions. The gelation time of the hydrogels shrank from 80 to 49 s, and the swelling ratio increases from 3.7 to 6.6, along with the increase of OCAPS feed ratio gradually. The incorporation of OCAPS into the system also enhanced the mechanical property of the hydrogels. Compared with the controllable hydrogel without OCAPS, which failed to remain a certain shape for a long time, the nanocomposite hydrogels exhibited an outstanding compression property, and 68.4% of stain, 4.1 kPa of modulus, 97.9 kPa of strength when 40.0 wt% OCAPS was loaded. The rheological investigations suggested that the hydrogels possessed a very stable network, hence a self-healing property. Moreover, the result of Bovine serum albumin (BSA) load and release experiments demonstrated much improved drug load efficiency and cumulative drug release percentage of the nanocomposite hydrogels; the in-vitro degradation and cytotoxicity tests exhibited perfect biodegradability and biocompatibility of the hydrogels. All of these results demonstrate that the OCAPS and polysaccharides based hydrogels endow sound applications in drug carrier and tissue engineering materials.