Min Suk Shim

Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery

In recent years, there have been major advances and increasing amounts of research on the utilization of natural polymeric materials as drug delivery vehicles due to their biocompatibility and biodegradability. Seaweed polysaccharides are abundant resources and have been extensively studied for several biological, biomedical, and functional food applications. The exploration of seaweed polysaccharides for drug delivery applications is still in its infancy. Alginate, carrageenan, fucoidan, ulvan, and laminarin are polysaccharides commonly isolated from seaweed. These natural polymers can be converted into nanoparticles (NPs) by different types of methods, such as ionic gelation, emulsion, and polyelectrolyte complexing. Ionic gelation and polyelectrolyte complexing are commonly employed by adding cationic molecules to these anionic polymers to produce NPs of a desired shape, size, and charge. In the present review, we have discussed the preparation of seaweed polysaccharide-based NPs using different types of methods as well as their usage as carriers for the delivery of various therapeutic molecules (e.g., proteins, peptides, anti-cancer drugs, and antibiotics). Seaweed polysaccharide-based NPs exhibit suitable particle size, high drug encapsulation, and sustained drug release with high biocompatibility, thereby demonstrating their high potential for safe and efficient drug delivery.

Preparation and characterization of chitosan-natural nano hydroxyapatite-fucoidan nanocomposites for bone tissue engineering.

Solid three dimensional (3D) composite scaffolds for bone tissue engineering were prepared using the freeze-drying method. The scaffolds were composed of chitosan, natural nano-hydroxyapatite (nHA) and fucoidan in the following combinations: chitosan, chitosan-fucoidan, chitosan-nHA, and chitosan-nHA-fucoidan. Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and optical microscopy (OM) were used to determine the physiochemical constituents and the morphology of the scaffolds. The addition of nHA into the chitosan-fucoidan composite scaffold reduced the water uptake and water retention. FT-IR analysis confirmed the presence of a phosphate group in the chitosan-nHA-fucoidan scaffold. This group is present because of the presence of nHA (isolated via alkaline hydrolysis from salmon fish bones). Microscopic results indicated that the dispersion of nHA and fucoidan in the chitosan matrix was uniform with a pore size of 10-400μm. The composite demonstrated a suitable micro architecture for cell growth and nutrient supplementation. This compatibility was further elucidated in vitro using periosteum-derived mesenchymal stem cells (PMSCs). The cells demonstrated high biocompatibility and excellent mineralization for the chitosan-nHA-fucoidan scaffold. We believe that a chitosan-nHA-fucoidan composite is a promising biomaterial for the scaffold that can be used for bone tissue regeneration.

Antimicrobial and anticancer activities of porous chitosan-alginate biosynthesized silver nanoparticles

The main aim of this study was to obtain porous antimicrobial composites consisting of chitosan, alginate, and biosynthesized silver nanoparticles (AgNPs). Chitosan and alginate were used owing to their pore-forming capacity, while AgNPs were used for their antimicrobial property. The developed porous composites of chitosan-alginate-AgNPs were characterized using Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy, X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). The FT-IR results revealed the presence of a strong chemical interaction between chitosan and alginate due to polyelectrolyte complex; whereas, the XRD results confirmed the presence of AgNPs in the composites. The dispersion of AgNPs in the porous membrane was uniform with a pore size of 50-500μm. Antimicrobial activity of the composites was checked with Escherichia coli and Staphylococcus aureus. The developed composites resulted in the formation of a zone of inhibition of 11±1mm for the Escherichia coli, and 10±1mm for Staphylococcus aureus. The bacterial filtration efficiency of chitosan-alginate-AgNPs was 1.5-times higher than that of the chitosan-alginate composite. The breast cancer cell line MDA-MB-231 was used to test the anticancer activity of the composites. The IC50 value of chitosan-alginate-AgNPs on MDA-MB-231 was 4.6mg. The developed chitosan-alginate-AgNPs composite showed a huge potential for its applications in antimicrobial filtration and cancer treatment.

Antimicrobial, Antioxidant, and Anticancer Activities of Biosynthesized Silver Nanoparticles Using Marine Algae Ecklonia cava

Green synthesis of silver nanoparticles (AgNPs) has gained great interest as a simple and eco-friendly alternative to conventional chemical methods. In this study, AgNPs were synthesized by using extracts of marine algae Ecklonia cava as reducing and capping agents. The formation of AgNPs using aqueous extract of Ecklonia cava was confirmed visually by color change and their surface plasmon resonance peak at 418 nm, measured by UV-visible spectroscopy. The size, shape, and morphology of the biosynthesized AgNPs were observed by transmission electron microscopy and dynamic light scattering analysis. The biosynthesized AgNPs were nearly spherical in shape with an average size around 43 nm. Fourier transform-infrared spectroscopy (FTIR) analysis confirmed the presence of phenolic compounds in the aqueous extract of Ecklonia cava as reducing and capping agents. X-ray diffraction (XRD) analysis was also carried out to demonstrate the crystalline nature of the biosynthesized AgNPs. Antimicrobial results determined by an agar well diffusion assay demonstrated a significant antibacterial activity of the AgNPs against Escherichia coli and Staphylococcus aureus. Antioxidant results determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay revealed an efficient antioxidant activity of the biosynthesized AgNPs. The biosynthesized AgNPs also exhibited a strong apoptotic anticancer activity against human cervical cancer cells. Our findings demonstrate that aqueous extract of Ecklonia cava is an effective reducing agent for green synthesis of AgNPs with efficient antimicrobial, antioxidant, and anticancer activities.

Preparation of piperlongumine-loaded chitosan nanoparticles for safe and efficient cancer therapy

Development of biocompatible nanocarriers has gained much attention for cancer therapy because they can enhance cellular uptake and bioavailability of anticancer drugs with low toxicity. Chitosan has been intensively explored for biocompatible drug carriers due to high biodegradability and low toxicity. In this study, chitosan was used to synthesize biocompatible nanocarriers that can stably encapsulate piperlongumine (PL), a hydrophobic anticancer drug with cancer-specific antiproliferative activity via modulation of intracellular reactive oxygen species (ROS) in cancer cells. The PL-loaded chitosan nanoparticles (PL–CSNPs) prepared via ionic gelation showed an average particle size around 361 nm. The PL loading efficiency of the PL–CSNPs was 12 ± 2%. A drug release study revealed that the release of PL from the CSNPs was sustainable and pH-dependent. The PL–CSNPs showed efficient cytotoxicity against human gastric carcinoma (AGS) cells via dramatic increase of intracellular ROS leading to cell apoptosis. This study demonstrates that CSNPs are promising drug carriers for safe and effective PL delivery that can mediate efficient anticancer activity against gastric cancer cells.

Chitosan as a vehicle for growth factor delivery: Various preparations and their applications in bone tissue regeneration

The replacement of conventional autografts and allografts by bone fragments constructed from alternate materials, cells, and molecules (growth factors, drugs, etc.) is an exciting prospect in the field of bone tissue engineering. Bone morphogenetic protein-2 (BMP-2) is a growth factor that has been extensively studied from this point of view. This review analyzes the relevance of chitosan and its derivatives and composites with various materials such as ceramics, heparin, silica, stem cells, titanium implants, etc., in terms of delivering BMP-2 for the purpose of bone regeneration. Chitosan offers the versatility to be modified into any shapes or sizes including conversion to nanoparticles, microspheres, nanofibers, porous scaffolds, and films. The results presented in this review clearly demonstrate that chitosan-based materials are biocompatible and have the potential to systematically and sustainably release BMP-2 where required. This release results in enhanced cell proliferation levels, enhancement of alkaline phosphatase activity, increased differentiation as well as increased mineralization under in vitro and in vivo conditions. This review also shines a spotlight on the currently developed chitosan-based products that are being used for BMP-2 delivery.

Bone response to calcium phosphate coatings for dental implants

Abstract The ultimate goal of titanium dental implants is to obtain bioactive fixation between the implants and the native surrounding bone. The osseointegration of titanium dental implants is critically dependent on the mechanical and biocompatible properties of the implant surfaces. The medical grade titanium has good biocompatibility and excellent mechanical properties, except the lack of bioactive surface property. Despite its successful use, there is still room for improvement, with respect to faster bone healing or better healing in compromised tissues and conditions. Surface modification of dental implants has proved to accelerate the osseointegration. Rough surfaced implants increase bone-to-implant contact and speed up bone apposition. Among several methods being introduced to produce a rough surfaced implant, coating with calcium phosphate (CaP) has proved to be successful. CaP ceramics are known for their biocompatibility and osteoconductive properties and have been commonly used as coating materials to dental implants. The CaP bioceramics could promote implant–bone fixation due to their chemical and crystallographic similarity to the bone. Currently, CaP bioceramics are used to coat titanium implant and can endow the mechanical strength of metals with the excellent biological properties. Even though a stable coating can be advantageous in maintaining the firm bonding of bone to the implant, concern exists about the long-term ability of hydroxyapatite coatings to sustain the shear loads that arise at the implant–bone interface. The chapter outlines the various CaP-coating methods, detailed account of the bone–implant interface, drawbacks and avenues for future research in this area.

Fabrication of dual stimuli-responsive multicompartmental drug carriers for tumor-selective drug release

There has been increasing attention to the development of multi-stimuli-responsive drug carriers for precisely controlled drug release at target disease areas. In this study, pH- and redox-responsive hybrid drug carriers were fabricated by using both ketal-based acid-cleavable precursors and disulfide-based reducible precursors via stop-flow lithography. pH- and redox-sensitive drug release of the dual stimuli-responsive hybrid particles was confirmed, demonstrating their feasibility for selective and efficient drug release into tumor tissues in acidic and highly reductive environments. It was also found that the drug release rate of the particles was fine-tuned by modulating monomer compositions in the precursor. Importantly, the dual stimuli-responsive hybrid particles exhibited synergistic, controlled drug release in complex stimuli (both pH and redox stimuli) environments. To achieve tumor-selective combination chemotherapy, multicompartmental drug carriers consist of an acid-degradable compartment and a reducible compartment, which can separately encapsulate individual model drugs in each of the compartments. The multicompartmental particles exhibited independent drug release upon exposure to the corresponding stimulus. The dual stimuli-responsive, multicompartmental particles are effective drug carriers for tumor-selective release of a drug cocktail, leading to synergistic combination chemotherapy.

Microfluidic fabrication of biocompatible poly(N-vinylcaprolactam)-based microcarriers for modulated thermo-responsive drug release

Various thermo-responsive polymers have been developed for controlled drug delivery upon the local application of external heat. The development of thermo-responsive polymers with high biocompatibility and tunable thermo-sensitivity is crucial for safe and efficient therapeutic application. In this study, thermo-responsive drug carriers featuring tunable thermo-sensitivities were synthesized using biocompatible poly(N-vinyl caprolactam) (PVCL) and stop-flow lithography. The PVCL-based particles showed selective drug release depending on temperature, illustrating their feasibility for on-demand controlled drug delivery. The volume phase transition temperature (VPTT) of the PVCL-based particles can be adjusted to vary from room temperature to body temperature by controlling their monomer compositions. In addition, modulated drug release was achieved by constructing multicompartments of different thermo-sensitivities within the PVCL particles. To accomplish thermo-responsive anticancer therapy, doxorubicin (DOX) was encapsulated into the PVCL particles as an anticancer drug. The DOX-loaded PVCL particles exhibited both thermo-responsive drug release and anticancer activity. This study demonstrates that thermo-responsive PVCL particles are highly promising carriers for safe and targeted anticancer therapy.

Hydroxyapatite from Cuttlefish Bone: Isolation, Characterizations, and Applications

Hydroxyapatite (HA), a bioceramic, is a widely utilized material for bone tissue repair and regeneration because of its excellent properties such as biocompatibility, exceptional mechanical strength, and osteoconductivity. HA can be obtained by both synthetic and natural means. Animal bones are often considered a promising natural resource for the preparation of pure HA for biological and biomedical applications. Cuttlefish bone, also called as cuttlebone, mainly consists of calcium carbonate, and pure HA can be produced by adding phosphoric acid or ammonium hydrogen phosphate to it. Recently, cuttlefish bone-derived HA has shown promising results in terms of bone tissue repair and regeneration. The synthesized cuttlefish bone-derived has shown excellent biocompatibility, cell proliferation, increased alkaline phosphate activity, and efficient biomineralization ability with mesenchymal stem cells and osteoblastic cells. To further improve the biological properties of cuttlefish bone-derived HA, bioglass, polycaprolactone, and polyvinyl alcohol were added to it, which gave better results in terms of cell proliferation and osteogenic differentiation. Cuttlefish bone-derived HA with polymeric substances provides excellent bone formation under in vivo conditions. The studies indicate that cuttlefish bone-derived HA, along with polymeric and, protein materials, will be promising biomaterials in the field of bone tissue regeneration.