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1.
AAPS PharmSciTech ; 19(8): 3763-3769, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30259401

ABSTRACT

To alleviate concerns in health security, emergency flu vaccine stockpiles are required for ensuring rapid availability of vaccines when needed. Cold chain preservation, at high cost and risk, is necessary to maintain vaccine efficacy. This study aimed to develop a dry, easily storable formula for influenza vaccine preparation. The formulation with mucoadhesive properties is expected to facilitate rapid delivery via nasal administration. Chitosan, a cationic polymer, was used as cryo-protectant and to promote mucoadhesion. Optimal concentrations and molecular weights of chitosan polymers were screened, with short chain chitosan (10 kDa) being most suitable. H1N1 dry powder, in different formulations, was prepared via freeze-drying. A series of cryo-protectants, trehalose (T), chitosan (C), fetal bovine serum (FBS; F), or a combination of these (TCF), were screened for their effects on prolonging vaccine shelf life. Physicochemical monitoring (particle size and zeta potential) of powders complexed with mucin revealed that the order of cryo-protectant mixing during preparation was of critical importance. Results indicated that the TCF formula retains its activity up to 1 year as indicated by TCID50 analysis. This approach was also successful at prolonging the shelf life of H3N2 vaccine, and has the potential for large-scale implementation, especially in developed countries where long-term storage of vaccines is problematic.


Subject(s)
Cell Adhesion/drug effects , Freeze Drying/standards , Influenza Vaccines/chemistry , Refrigeration/standards , Administration, Intranasal , Animals , Cell Adhesion/physiology , Cell Survival/drug effects , Cell Survival/physiology , Chick Embryo , Dogs , Dose-Response Relationship, Drug , Drug Compounding , Drug Storage/methods , Drug Storage/standards , Freeze Drying/methods , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/immunology , Influenza Vaccines/administration & dosage , Madin Darby Canine Kidney Cells , Particle Size , Powders , Refrigeration/methods
2.
Biomacromolecules ; 15(8): 2879-88, 2014 Aug 11.
Article in English | MEDLINE | ID: mdl-24956200

ABSTRACT

Highly fluorescent N-substituted 1-cyanobenz[f]isoindole chitosans (CBI-CSs) with various degrees of N-substitution (DS) were synthesized by reacting chitosan (CS) with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide under mild acidic conditions. Introduction of 1-cyanobenz[f]isoindole moieties into the CS backbone resulted in lowering of polymer thermal stability and crystallinity. The fluorescence quantum yield (Φf) of CBI-CS was found to be DS- and molecular-weight-dependent, with Φf decreasing as DS and molecular weight were increased. At similar DS values, CBI-CS exhibited 26 times higher Φf in comparison with fluorescein isothiocyanate-substituted chitosan (FITC-CS). CBI-CS/TPP nanoparticles were fabricated using an ionotropic gelation method in which pentasodium triphosphate (TPP) acted as a cross-linking agent. CS and CBI-CS exhibited low cytotoxicity to normal skin fibroblast cells over a concentration range of 0.1-1000 µg/mL, while an increased cytotoxicity level was evident in CBI-CS/TPP nanoparticles at concentrations greater than 100 µg/mL. In contrast with CBI-CS polymers, the CBI-CS/TPP nanoparticles exhibited lower fluorescence; however, confocal microscopy results showed that living normal skin fibroblast cells became fluorescent on nanoparticle uptake. These results suggest that CBI-CS and fabricated nanoparticles thereof may be promising fluorescence probes for live cell imaging.


Subject(s)
Chitosan , Fibroblasts/cytology , Fluorescent Dyes , Nanoparticles/chemistry , Chitosan/chemistry , Chitosan/pharmacology , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology , Humans , Microscopy, Fluorescence/methods
3.
J Microencapsul ; 31(6): 609-18, 2014.
Article in English | MEDLINE | ID: mdl-24861323

ABSTRACT

Fine-tuning the nanoscale structure and morphology of nanostructured lipid carriers (NLCs) is central to improving drug loading and stability of the particles. The role of surfactant charge on controlling the structure, the physicochemical properties and the stability of NLCs has been investigated using three surfactant types (cationic, anionic, non-ionic), and mixed surfactants. Either one, a mixture of two, or a mixture of three surfactants were used to coat the NLCs, with these classified as one, two and three surfactant systems, respectively. The mixed (two and three) surfactant systems produced smaller NLC particles and yielded NLCs with lower crystallinity than the one surfactant system. The combined effects of the ionic and the non-ionic surfactants may play a key role in assisting the lipid-oil mixing, as well as maintaining colloidal repulsion between NLC particles. In contrast, for the three surfactant system, the lipid-oil mixture in the NLCs appeared less homogenous. This was also reflected in the results of the stability study, which indicated that NLC particle sizes in two surfactant systems appeared to be retained over longer periods than for other surfactant systems.


Subject(s)
Drug Carriers/chemistry , Lipids/chemistry , Nanostructures/chemistry , Surface-Active Agents/chemistry , Colloids , Oils/chemistry
4.
AAPS PharmSciTech ; 15(5): 1105-15, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24851817

ABSTRACT

Silver nanoparticles (AgNPs)-loaded alginate beads embedded in gelatin scaffolds were successfully prepared. The AgNPs-loaded calcium alginate beads were prepared by electrospraying method. The effect of alginate concentration and applied voltage on shape and diameter of beads was studied. The diameter of dry AgNPs-loaded calcium alignate beads at various concentrations of AgNO3 ranged between 154 and 171 µm. The AgNPs-loaded calcium alginate beads embedded in gelatin scaffolds were fabricated by freeze-drying method. The water swelling and weight loss behaviors of the AgNPs-loaded alginate beads embedded in gelatin scaffolds increased with an increase in the submersion time. Moreover, the genipin-cross-linked gelatin scaffolds were proven to be nontoxic to normal human dermal fibroblasts, suggesting their potential uses as wound dressings.


Subject(s)
Alginates/chemistry , Gelatin/chemistry , Metal Nanoparticles/chemistry , Silver/chemistry , Cell Survival/drug effects , Cross-Linking Reagents , Excipients/chemistry , Freeze Drying , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Iridoids/chemistry , Particle Size
5.
Heliyon ; 10(8): e29444, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38628769

ABSTRACT

Fragmentation of ß-glucans secreted by the fungus Ophiocordyceps dipterigena BCC 2073 achieved by microfluidization was investigated. The degree of ß-glucan fragmentation was evaluated based on the average number of chain scissions (α). The effects on the α value of experimental variables like solid concentration of the ß-glucan suspension, interaction chamber pressure, and number of passes through the microfluidizer were examined. Kinetic studies were conducted using the relationships of the α and suspension viscosity values with the number of passes. Evidence indicated that α increases with the interaction chamber pressure and the number of passes, whereas the solid concentration shows the inverted effect. Kinetic data indicated that the fragmentation rate increases with ß-glucan solid concentration and interaction chamber pressure. Furthermore, since ß-glucan molecular weight is a key factor determining its biological activity, the effect of ß-glucans of different molecular weights produced by fragmentation on tumor necrosis factor (TNF)-α-stimulating activity in THP-1 human macrophage cells was investigated. Evidence suggested that ß-glucans have an immunostimulating effect on macrophage function, in the absence of cytotoxic effects. Indeed, ß-glucans characterized by a range of molecular weights produced via microfluidization exhibited promise as immunostimulatory agents.

6.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112211, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34800865

ABSTRACT

The consumption of foods rich in antioxidants, vitamins, minerals including carotenoids etc. can boost the immune system to help fight off various infections including SARS- CoV 2 and other viruses. Carotenoids have been gaining attention particularly in food and pharmaceutical industries owing to their diverse functions including their role as pro-vitamin A activity, potent antioxidant properties, and quenching of reactive oxygen (ROS), such as singlet oxygen and lipid peroxides within the lipid bilayer of the cell membrane. Nevertheless, carotenoids being lipophilic, have poor solubility in aqueous medium and are also chemically instable. They are susceptible to degrade under stimuli environmental conditions during food processing, storage and gastrointestinal passage. They also exhibit poor oral bioavailability, thus, their applications in aqueous-based foods are limited. As a consequent, suitable delivery systems including colloids-based are needed to enhance the solubility, stability and bioavailability of carotenoids. This review presents challenges of incorporation and delivery of carotenoids focusing on stability and factors affecting bioavailability. Furthermore, designed factors impacting bioaccessibility and bioavailability of carotenoids using emulsion-based delivery systems are explicitly explained. Each delivery system exhibits its own advantages and disadvantages; thus, the delivery systems should be designed based on their targets and their further applications.


Subject(s)
COVID-19 , Carotenoids , Biological Availability , Emulsions , Humans , SARS-CoV-2
7.
Colloids Surf B Biointerfaces ; 220: 112920, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36279763

ABSTRACT

Water soluble quaternized cyclodexrin grafted chitosan (QCD-g-CS) was synthesized by combining both beneficial properties of ß-cyclodextrin (ß-CD) and the chitosan (CS) backbone. The chitosan backbone exhibits positive charges, while the ß-CD moieties are available to include hydrophobic guest molecules into the cavity. The present work demonstrates a formation of nanocomplexes by simple mixing of the cationic QCD-g-CS with three different molecular weights of anionic Hyaluronic acid (low, medium and high HA; LHA, MHA and HHA, respectively). The HA is well-known on providing hydration to the skin and normalize keratinization. However, its strong hydrophilicity limits skin absorption. The polyelectrolyte nanocomplexes between QCD-g-CS and HA formed through the electrostatic interactions were confirmed by FTIR. Particle size of HA nanocomplexes were greater than that of free QCD-g-CS and increased with an increase in HA content. The complex of LHA and MHA improve the water retention capacity as well as ability to control the release of HA to be slower than the original HA. The release of both LHA and MHA from their complexes were both limited diffusion kinetics. Pronounced effect of small particle sizes of LHA complexes was found to benefit skin penetration. Clinical study indicated that LHA complexes improved skin texture and elasticity due to an increase in skin hydration. It is suggested that the QCD-g-CS in combination with anionic hydrophilic HA can be used as a promising polysaccharide-based skin delivery system.


Subject(s)
Chitosan , Cyclodextrins , Chitosan/chemistry , Hyaluronic Acid/chemistry , Molecular Weight , Water/chemistry
8.
Carbohydr Res ; 504: 108336, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33964507

ABSTRACT

The development of hybrid polysaccharide-protein complexes as Pickering emulsion stabilizers has attracted increasing research interest in recent years. This work presents an eco-friendly surface modification strategy to functionalize hydrophilic cellulose nanocrystals (CNC) using hydrophobic soy protein isolate (SPI) via mussel adhesive-inspired poly (l-dopa) (PLD) to develop improved nanoconjugates as stabilizers for oil-in-water Pickering emulsion. The physicochemical properties of the CNC-PLD-SPI nanoconjugate were evaluated by solid-state 13C NMR, FT-IR, TGA, XRD, contact angle analysis, and TEM. The modified CNC (conjugation content of 38.22 ± 1.21%) had lowered crystallinity index, higher thermal stability, and more hydrophobic than unmodified CNC, with an average particle size of 309.9 ± 8.0 nm. Use of amphiphilic CNC-PLD-SPI nanoconjugate with greater conformational flexibility as Pickering stabilizer produced oil-in-water emulsions with greater physical stability.


Subject(s)
Cellulose , Emulsions , Nanoconjugates , Soybean Proteins
9.
Plants (Basel) ; 10(2)2021 Jan 26.
Article in English | MEDLINE | ID: mdl-33530608

ABSTRACT

Rising world population is expected to increase the demand for nitrogen fertilizers to improve crop yield and ensure food security. With existing challenges on low nutrient use efficiency (NUE) of urea and its environmental concerns, controlled release fertilizers (CRFs) have become a potential solution by formulating them to synchronize nutrient release according to the requirement of plants. However, the most significant challenge that persists is the "tailing" effect, which reduces the economic benefits in terms of maximum fertilizer utilization. High materials cost is also a significant obstacle restraining the widespread application of CRF in agriculture. The first part of this review covers issues related to the application of conventional fertilizer and CRFs in general. In the subsequent sections, different raw materials utilized to form CRFs, focusing on inorganic and organic materials and synthetic and natural polymers alongside their physical and chemical preparation methods, are compared. Important factors affecting rate of release, mechanism of release and mathematical modelling approaches to predict nutrient release are also discussed. This review aims to provide a better overview of the developments regarding CRFs in the past ten years, and trends are identified and analyzed to provide an insight for future works in the field of agriculture.

10.
Nanotechnology ; 21(12): 125102, 2010 Mar 26.
Article in English | MEDLINE | ID: mdl-20182010

ABSTRACT

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of gamma-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the gamma-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ((1)H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the (1)H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of gamma-oryzanol inside the lipid nanoparticles, the (1)H-NMR revealed that the chemical shifts of the liquid lipid in gamma-oryzanol loaded systems were found at rather higher field than those in gamma-oryzanol free systems, suggesting incorporation of gamma-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of gamma-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of gamma-oryzanol and lipids (solid and liquid) inside the lipid nanoparticle systems are proposed.


Subject(s)
Drug Carriers/chemistry , Nanoparticles/chemistry , Palmitates/chemistry , Phenylpropionates/chemistry , Triglycerides/chemistry , Analysis of Variance , Area Under Curve , Drug Delivery Systems , Microscopy, Atomic Force , Nuclear Magnetic Resonance, Biomolecular , Particle Size , Powder Diffraction , Spectrum Analysis, Raman , Thermodynamics
11.
J Microencapsul ; 27(5): 436-46, 2010.
Article in English | MEDLINE | ID: mdl-20001503

ABSTRACT

The objective of this work has been the microencapsulation of Asiatic Pennywort (AP) extract with lecithin from soybean. The effect of various quantities of non-ionic surfactant (Montanov82) on liposomes upon physicochemical characteristics as well as their in vitro bio-activities was investigated. An addition of surfactant resulted in a decrease in particle size and an increase in percentage AP entrapment efficiency of liposomes. The surfactant-loaded liposomes demonstrated higher stability than surfactant-free liposomes where higher percentage AP remaining of liposomes can be achieved depending on surfactant concentration. No significant difference was found on AP release profiles among varied surfactant concentrations, although a presence of surfactant resulted in prolonged AP release rate. Liposomal AP with 20% w/w surfactant or higher demonstrated low cytotoxicity, a stronger anti-oxidation effect and collagen production on dermal fibroblast cells when compared with free AP and surfactant-free liposomes, possibly due to better cell internalization and less AP degradation in cells.


Subject(s)
Antioxidants/administration & dosage , Antioxidants/pharmacology , Centella/chemistry , Fibroblasts/drug effects , Liposomes/chemistry , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Cell Line , Cell Survival/drug effects , Collagen/metabolism , Drug Compounding , Fibroblasts/metabolism , Humans , Lecithins/chemistry , Particle Size , Glycine max/chemistry , Surface-Active Agents
12.
Colloids Surf B Biointerfaces ; 196: 111270, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32777659

ABSTRACT

Cisplatin (Cis) is a widely used chemotherapeutic drug for cancer treatment. However, toxicities and drug resistance limit the use of cisplatin. This study was aimed to improve cisplatin delivery using a targeting strategy to reduce the toxicity. In the present study, combinations of poly lactic-co-glycolic acids (PLGA) and liposomes were used as carriers for cisplatin delivery. In addition, to target the nanoparticle towards tumor cells, the liposome was conjugated with Avastin®, an anti-VEGF antibody. Cisplatin was loaded into PLGA using the double emulsion solvent evaporation method and further encapsulated in an Avastin® conjugated liposome (define herein as L-PLGA-Cis-Avastin®). Their physicochemical properties, including particle size, ζ-potential, encapsulation efficiency and drug release profiles were characterized. In addition, a study of the efficiency of tumor targeted drug delivery was conducted with cervical tumor bearing mice via intravenous injection. The therapeutic effect was examined in a 3D spheroid of SiHa cell line and SiHa cells bearing mice. The L-PLGA-Cis-Avastin® prompted a significant effect on cell viability and triggered cytotoxicity of SiHa cells. A cell internalization study confirmed that the L-PLGA-Cis-Avastin® had greater binding specificity to SiHa cells than those of L-PLGA-Cis or free drug, resulting in enhanced cellular uptake. Tumor targeting specificity was finally confirmed in xenograft tumors. Taken together, this nanoparticle could serve as a promising specific targeted drug for cervical cancer treatment.


Subject(s)
Nanoparticles , Uterine Cervical Neoplasms , Animals , Cell Line, Tumor , Cisplatin , Drug Carriers , Female , Glycols , Humans , Liposomes , Mice , Particle Size , Uterine Cervical Neoplasms/drug therapy
13.
Sci Rep ; 9(1): 8278, 2019 06 04.
Article in English | MEDLINE | ID: mdl-31164665

ABSTRACT

Gold nanoparticles (AuNPs) have been extensively used as nanomaterials for theranostic applications due to their multifunctional characteristics in therapeutics, imaging, and surface modification. In this study, the unique functionalities of exosome-derived membranes were combined with synthetic AuNPs for targeted delivery to brain cells. Here, we report the surface modification of AuNPs with brain-targeted exosomes derived from genetically engineered mammalian cells by using the mechanical method or extrusion to create these novel nanomaterials. The unique targeting properties of the AuNPs after fabrication with the brain-targeted exosomes was demonstrated by their binding to brain cells under laminar flow conditions as well as their enhanced transport across the blood brain barrier. In a further demonstration of their ability to target brain cells, in vivo bioluminescence imaging revealed that targeted-exosome coated AuNPs accumulated in the mouse brain after intravenous injection. The surface modification of synthetic AuNPs with the brain-targeted exosome demonstrated in this work represents a highly novel and effective strategy to provide efficient brain targeting and shows promise for the future in using modified AuNPs to penetrate the brain.


Subject(s)
Blood-Brain Barrier/drug effects , Brain/drug effects , Exosomes/chemistry , Metal Nanoparticles/chemistry , Animals , Biological Transport/genetics , Drug Delivery Systems , Exosomes/genetics , Gold/chemistry , Humans , Metal Nanoparticles/administration & dosage , Mice , Neurons/drug effects
14.
Int J Pharm ; 538(1-2): 21-29, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29225100

ABSTRACT

In this study, the inclusion complex formation between α-mangostin and water-soluble quaternized ß-CD grafted-chitosan (QCD-g-CS) was investigated. Inclusion complex formation with encapsulation efficiency (%EE) of 5, 15 and 75% can be varied using high speed homogenizer. Tuning %EE plays a role on physicochemical and biological properties of α-mangostin/QCD-g-CS complex. Molecular dynamics simulations indicate that α-mangostin is included within the hydrophobic ß-CD cavity and being absorbed on the QCD-g-CS surface, with these results being confirmed by Fourier transform infrared (FTIR) spectroscopy. Probing the release characteristics of the inclusion complex at various %EE (5%, 15% and 75%) in simulated saliva (pH 6.8) demonstrated that α-mangostin release rates were dependent on % EE (order 5% > 15% > 75%). Additionally, higher antimicrobial and anti-inflammation activities were observed for the inclusion complex than those of free α-mangostin due to enhance the solubility of α-mangostin through the inclusion complex with QCD-g-CS.


Subject(s)
Chemistry, Pharmaceutical/methods , Chitosan/chemistry , Xanthones/administration & dosage , beta-Cyclodextrins/chemistry , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Line , Drug Carriers/chemistry , Drug Liberation , Humans , Hydrophobic and Hydrophilic Interactions , Molecular Dynamics Simulation , Saliva/metabolism , Solubility , Spectroscopy, Fourier Transform Infrared , Water/chemistry , Xanthones/chemistry , Xanthones/pharmacology
15.
Theriogenology ; 108: 167-175, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29223654

ABSTRACT

The overpopulation of free-roaming companion animals has become the global crisis. The development and application of a suitable, effective, non-surgical approach for animal sterilization would have an enormous advantage over the current surgical method. The main purpose of this study was to develop and evaluate a novel nanomedicine-based chemosterilant for non-surgical castration of male companion animals. In this study, we first sought to investigate the testicular toxicity of different apoptosis-inducing agents. We next synthesized and characterized nano-sized particles which encapsulated the most potent testicular toxicants and evaluated in vitro sterilant properties. Our result showed that doxorubicin exhibited the highest cytotoxic activity against mouse spermatogenic cells. We therefore synthesized and characterized doxorubicin-encapsulated nanoemulsion. The negatively charged particle of doxorubicin-encapsulated nanoemulsion exhibited the anti-proliferative activity towards spermatogetic cells. Apoptosis studies revealed activation of Caspases 3 and 7 as well as annexin V expression. In addition, doxorubicin-encapsulated nanoemulsion exhibited anti-inflammatory activity in lipopolysaccharide-stimulated macrophages. Cell death was observed following treatment of isolated and cultured rat seminiferous tubules with doxorubicin-encapsulated nanoemulsion. In conclusion, nanoemulsion can be a potential carrier for prolonged release and to enhance activity of doxorubicin that may have utility in non-surgical castration of male animals.


Subject(s)
Chemosterilants/administration & dosage , Doxorubicin/administration & dosage , Pets , Sterilization, Reproductive/veterinary , Animal Welfare , Animals , Apoptosis/drug effects , Cats , Dogs , Doxorubicin/therapeutic use , Germ Cells/drug effects , Male , Mice , Nanomedicine/methods , Rats , Seminiferous Tubules/drug effects , Sterilization, Reproductive/methods
16.
Colloids Surf B Biointerfaces ; 149: 301-311, 2017 Jan 01.
Article in English | MEDLINE | ID: mdl-27780087

ABSTRACT

A nanostructure lipid carrier (NLC) composed of solid, and liquid lipid as a core has been developed as a delivery system for hydrophobic drug molecules. The aim of this research was to fabricate an oleoyl-quaternized-chitosan (CS)-coated NLC, where the mucoadhesive property of nanoparticles is enhanced for more efficient drug delivery. NLC loaded with alpha-mangostin (AP), a model hydrophobic drug, were fabricated using a high pressure homogenization process and subsequently coated with CS. The fabricated nanoparticles showed particle sizes in the range of 200-400nm, with low polydispersity, high physical stability and excellent encapsulation efficiency (EE>90%). Additionally, in vitro viability, cytotoxicity and ability of NLC and CS-NLC to affect apoptosis in carcinoma Caco-2 cells were determined using the Triplex assay. Gene expressiom analysis were performed using quantitative reverse transcription Polymerase Chain Reaction (RT-qPCR). Moreover, in vivo toxicological testing of NLCs was conducted in zebrafish embryos. Results indicated that CS-NLC provieded high cytotoxicity than NLC itself. In the case of AP loaded nanoparticles, NLC loaded with AP (AP-NLC), and CS-NLC loaded with AP (CS-AP-NLC) exhibited higher cytotoxicity to Caco-2 over Hela cells. These results indicate that CS-NLC shows enhanced cellular uptake but increased cytotoxicity characteristics over NLC and therefore careful optimization of dosage and loading levels in CS-NLC is needed to allow cancer cell targeting, and for exploiting the potential of these systems in cancer therapy.


Subject(s)
Chitosan/analogs & derivatives , Drug Carriers , Nanoparticles/chemistry , Protein Kinase Inhibitors/pharmacology , Xanthones/pharmacology , Apoptosis/drug effects , Caco-2 Cells , Cell Survival/drug effects , Cyclin D1/genetics , Cyclin D1/metabolism , Cyclin-Dependent Kinase 4/genetics , Cyclin-Dependent Kinase 4/metabolism , Drug Compounding , Drug Liberation , Gene Expression/drug effects , HeLa Cells , Humans , Hydrophobic and Hydrophilic Interactions , Nanoparticles/ultrastructure , Particle Size , Protein Kinase Inhibitors/chemistry , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Surface Properties , Xanthones/chemistry , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , bcl-X Protein/genetics , bcl-X Protein/metabolism
17.
Sci Rep ; 7(1): 16234, 2017 11 24.
Article in English | MEDLINE | ID: mdl-29176590

ABSTRACT

The overpopulation of abandoned and stray companion animals has become a global crisis. The main purpose of this study was to develop a novel nanomedicine-based antifertility compound for non-surgical castration of male animals. Mangosteen (Garcinia mangostana L) pericarp extract has been shown to exhibit anti-fertility property. α-mangostin (AM)-loaded nanostructured lipid carrier (AM-NLC) was developed to improve male germ cell apoptosis. This study was conducted to investigate physicochemical properties of AM-NLC and determine the biological effects of AM-NLC on spermatogonia cells and testicular explants obtained from castrated testes. AM-NLC was produced through a hot homogenization technique. The negatively charged particle of AM-NLC was nano-sized with a narrow dispersity. AM-NLC exhibited antiproliferative activity towards spermatogonium cells. It induced apoptosis in the cells. In addition, AM-NLC exhibited anti-inflammatory activities in lipopolysaccharide-activated macrophages. Abnormal anatomy of seminiferous tubule was noted following treatment of testicular explant with AM-NLC. This nanomedicine-based sterilant would be a promising platform that may have utility in non-surgical castration of male animals by intra-testicular injection.


Subject(s)
Nanoparticles/chemistry , Spermatogonia/drug effects , Sterilization, Reproductive/veterinary , Xanthones/pharmacology , Animals , Apoptosis , Cats , Cells, Cultured , Male , Mice , RAW 264.7 Cells , Spermatogonia/cytology , Sterilization, Reproductive/methods , Testis/cytology , Testis/drug effects , Xanthones/administration & dosage
18.
J Colloid Interface Sci ; 480: 240-248, 2016 Oct 15.
Article in English | MEDLINE | ID: mdl-27442151

ABSTRACT

This study emphasizes the development of a novel surface modified liposome as an anticancer drug nanocarrier. Quaternized N,O-oleoyl chitosan (QCS) was synthesized and incorporated into liposome vesicles, generating QCS-liposomes (Lip-QCS). The Lip-QCS liposomes were spherical in shape (average size diameter 171.5±0.8nm), with a narrow size distribution (PDI 0.1±0.0) and zeta potential of 11.7±0.7mV. In vitro mucoadhesive tests indicated that Lip-QCS possesses a mucoadhesive property. Moreover, the presence of QCS was able to induce the cationic charge on the surface of liposome. Cellular internalization of Lip-QCS was monitored over time, with the results revealing that the cell entry level of Lip-QCS was elevated at 24h. Following this, Lip-QCS were then employed to load cisplatin, a common platinum-containing anti-cancer drug, with a loading efficiency of 27.45±0.78% being obtained. The therapeutic potency of the loaded Lip-QCS was investigated using a 3D spheroid cervical cancer model (SiHa) which highlighted their cytotoxicity and apoptosis effect, and suitability as a controllable system for sustained drug release. This approach has the potential to assist in development of an effective drug delivery system against cervical cancer.


Subject(s)
Antineoplastic Agents/administration & dosage , Chitosan/chemistry , Cisplatin/administration & dosage , Drug Delivery Systems , Nanostructures/chemistry , Phospholipids/chemistry , Uterine Cervical Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Cisplatin/pharmacology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Liposomes/chemistry , Molecular Structure , Structure-Activity Relationship , Uterine Cervical Neoplasms/pathology
19.
Int J Biol Macromol ; 84: 472-80, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26552020

ABSTRACT

Two guest molecules (eugenol and (-)-menthol) were investigated on inclusion complex formation with water-soluble quaternized ß-CD grafted with chitosan (QCD-g-CS). The inclusion complexes were prepared at varying mole ratios between eugenol or (-)-menthol and ß-CD (substituted on QCD-g-CS) by a conventional shaking method and obtained as solid powder by freeze-drying process. The results showed that encapsulation efficiency %EE decreased with increasing of initial eugenol or (-)-menthol loading whereas %loading increased with increasing of initial eugenol or (-)-menthol loading. The results indicated that inclusion complex formation between eugenol and QCD-g-CS was more favorable than that of (-)-menthol. To clarify this mechanism, molecular dynamics simulations were performed to explore their binding energy, solvation energy and total free energy of those complexes. It was found that the total free energy (ΔG) of eugenol and (-)-menthol against QCD-g-CS (mole ratio of 1) in water-explicit system were -2108.91 kJ/mol and -344.45 kJ/mol, respectively. Moreover, molecular dynamic simulation of eugenol absorbed on surface QCD-g-CS (-205.73 kJ/mol) was shown to have a higher negative value than that of (-)-menthol on QCD-gCS (3182.31 kJ/mol). Furthermore, the release characteristics of the encapsulated powder were also investigated in simulated saliva pH 6.8 at 32 °C. The results suggested that (-)-menthol had higher release rate from the complexes than eugenol. In all cases, the release characteristics for those guest molecules could be characterized by the limited-diffusion kinetics.


Subject(s)
Chitosan/chemistry , Eugenol/chemistry , Menthol/chemistry , beta-Cyclodextrins/chemistry , Calorimetry, Differential Scanning , Eugenol/administration & dosage , Menthol/administration & dosage , Models, Molecular , Molecular Conformation , Solubility , Spectroscopy, Fourier Transform Infrared , Thermodynamics , Water/chemistry
20.
Colloids Surf B Biointerfaces ; 130: 229-36, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-25937384

ABSTRACT

Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer.


Subject(s)
Acrylic Resins/chemistry , Adhesives/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Cell Adhesion , Cell Line, Tumor , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Delivery Systems , Endocytosis , Humans , Lactic Acid/pharmacology , Magnetic Resonance Spectroscopy , Microscopy, Confocal , Microscopy, Electron, Transmission , Mucins/chemistry , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Particle Size , Polyglycolic Acid/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer , Polyvinyl Alcohol/chemistry , Spectroscopy, Fourier Transform Infrared , Surface Properties
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