Zingiber officinale Roscoe Essential Oils-Loaded Chitosan Nanoparticles with Enhanced Bactericidal Efficacy against Burkholderia glumae in Rice.

Ginger essential oils (GEO) shows exceptional antimicrobial properties against plant pathogens. Due to its high volatility and low stability, it requires encapsulation to retain its effective properties. The GEO-Chitosan (GEO-CS) nanobactericide was developed using the ionic gelation method. The nanobactericides show particle diameters of 465, 28, 35, 48 and 500 nm when sodium tripolyphosphate (TPP) concentrations used in the preparation were 0.0, 0.5, 1.0, 2.0 and 4.0 %, respectively. The X-ray diffraction and the UV-vis studies revealed that the GEO was encapsulated into the chitosan nanoparticles with an encapsulation efficiency of around 46 % and a loading capacity of 27-34 %. The antibacterial activity of GEO-chitosan nanobactericide against Burkholderia glumae (Bg) was found to be 7.5-11.8 mm, with minimum inhibitory concentration and minimum bactericidal concentration values of 15.6 µl/mL and 31.25 µl/mL, respectively. Hence, these findings indicate that the prepared GEO-CS nanobactericides were found to be effective against Bg. This preliminary study is toward the development of new agronanobactericides using a natural product to control Bg.

Preparation, characterization, in vitro drug release and anti-inflammatory of thymoquinone-loaded chitosan nanocomposite.

In this study, we formulated Thymoquinone-loaded nanocomposites (TQ-NCs) using high-pressure homogenizer without sodium tripolyphosphate. The TQ-NCs were characterized and their anti-inflammatory determined by the response of the LPS-stimulated macrophage RAW 264.7 cells in the production of nitric oxide, prostaglandin E2, tumor necrosis factor-α, interleukin-6, and interleukin-1ß. The physicochemical properties of TQ-NC were determined using different machines. TQ was fully incorporated in the highly thermal stable nanoparticles. The nanoparticles showed rapid release of TQ in the acidic medium of the gastric juice. In medium of pH 6.8, TQ-NC exhibited sustained release of TQ over a period of 100 h. The results suggest that TQ-NC nanoparticles have potential application as parenterally administered therapeutic compound. TQ-NC effectively reduce production of inflammatory cytokines by the LPS-stimulated RAW 264.7 cells, indicating that they have anti-inflammatory properties. In conclusion, TQ-NC nanoparticles have the characteristics of efficient carrier for TQ and an effective anti-inflammatory therapeutic compound.

Graphene Oxide Loaded with Protocatechuic Acid and Chlorogenic Acid Dual Drug Nanodelivery System for Human Hepatocellular Carcinoma Therapeutic Application.

Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that responsible for 75-90% of all liver cancer in humans. Nanotechnology introduced the dual drug nanodelivery method as one of the initiatives in nanomedicine for cancer therapy. Graphene oxide (GO) loaded with protocatechuic acid (PCA) and chlorogenic acid (CA) have shown some anticancer activities in both passive and active targeting. The physicochemical characterizations for nanocomposites were conducted. Cell cytotoxicity assay and lactate dehydrogenase were conducted to estimate cell cytotoxicity and the severity of cell damage. Next, nanocomposite intracellular drug uptake was analyzed using a transmission electron microscope. The accumulation and localization of fluorescent-labelled nanocomposite in the human hepatocellular carcinoma (HepG2) cells were analyzed using a fluorescent microscope. Subsequently, Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Cell cycle arrest was ascertained at the G2/M phase. There was the depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. In conclusion, HepG2 cells treated with a graphene oxide-polyethylene glycol (GOP)-PCA/CA-FA dual drug nanocomposite exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid, chlorogenic acid and GOP-PCA/CA nanocomposite, may be due to the utilization of a folic acid-targeting nanodrug delivery system.

Hexaconazole-Micelle Nanodelivery System Prepared Using Different Surfactants for Ganoderma Antifungal Application.

Reports on fungicide-based agronanochemicals in combating disastrous basal stem rot disease in the oil palm industry are scant. Herein, we describe the potential of fungicide nanodelivery agents based on hexaconazole-micelle systems produced using three different surfactants; sodium dodecylbenze sulfonate (SDBS), sodium dodecyl sulfate (SDS) and Tween 80 (T80). The resulting nanodelivery systems were characterized and the results supported the encapsulation of the fungicide into the micelles of the surfactants. We have investigated in detail the size-dependent effects of the as-synthesized micelles towards the inhibition growth of Ganoderma Boninense fungi. All the nanodelivery systems indicate that their size decreased as the surfactant concentration was increased, and it directly affects the fungal inhibition. It was also found that Tween 80, a non-ionic surfactant gave the lowest effective concentration, the EC50 value of 2, on the pathogenic fungus Ganoderma boninense compared to the other anionic surfactants; SDBS and SDS. This study opens up a new generation of agronanofungicide of better efficacy for Ganoderma disease treatment.

Morphological Changes and Cellular Uptake of Functionalized Graphene Oxide Loaded with Protocatechuic Acid and Folic Acid in Hepatocellular Carcinoma Cancer Cell.

The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to ensure successful utilisation of the nanocomposites. Studies have suggested that the nanocomposites' ability to permeate into biological cells is attributable to their well-defined physicochemical properties with nanoscale size, which is relevant to the nanoscale components of biology and cellular organelles. The functionalized graphene oxide coated with polyethylene glycol, loaded with protocatechuic acid and folic acid (GOP-PCA-FA) nanocomposite intracellular uptake was analysed using transmission electron microscope. The accumulation of fluorescent-labelled nanocomposites in the HepG2 cell was also analysed using a fluorescent microscope. In vitro cellular uptake showed that there was uptake of the drug from 24 h into the cells and the release study using fluorescently tagged nanocomposite demonstrated that release and accumulation were observed at 24 h and 48 h. Moreover, the migration ability of tumor cells is a key step in tumor progression which was observed 48 h after treatment. The GOP serves as a potential nanocarrier system which is capable of improving the therapeutic efficacy of drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated drugs. Nonetheless, it is essential to analyse the translocation of our newly developed GOP-PCA-FA, and its efficiency for drug delivery, effective cellular uptake, and abundant intracellular accumulation would be compromised by possible untoward side effects.

Chitosan-Based Agronanochemicals as a Sustainable Alternative in Crop Protection.

The rise in the World's food demand in line with the increase of the global population has resulted in calls for more research on the production of sustainable food and sustainable agriculture. A natural biopolymer, chitosan, coupled with nanotechnology could offer a sustainable alternative to the use of conventional agrochemicals towards a safer agriculture industry. Here, we review the potential of chitosan-based agronanochemicals as a sustainable alternative in crop protection against pests, diseases as well as plant growth promoters. Such effort offers better alternatives: (1) the existing agricultural active ingredients can be encapsulated into chitosan nanocarriers for the formation of potent biocides against plant pathogens and pests; (2) the controlled release properties and high bioavailability of the nanoformulations help in minimizing the wastage and leaching of the agrochemicals' active ingredients; (3) the small size, in the nanometer regime, enhances the penetration on the plant cell wall and cuticle, which in turn increases the argochemical uptake; (4) the encapsulation of agrochemicals in chitosan nanocarriers shields the toxic effect of the free agrochemicals on the plant, cells and DNA, thus, minimizing the negative impacts of agrochemical active ingredients on human health and environmental wellness. In addition, this article also briefly reviews the mechanism of action of chitosan against pathogens and the elicitations of plant immunity and defense response activities of chitosan-treated plants.

Dual Drugs Anticancer Nanoformulation using Graphene Oxide-PEG as Nanocarrier for Protocatechuic Acid and Chlorogenic Acid.

BACKGROUND: The chemotherapy of cancer has been complicated by poor bioavailability, adverse side effects, high dose requirement, drug resistance and low therapeutic indices. Cancer cells have different ways to inhibit the chemotherapeutic drugs, use of dual/multiple anticancer agents may be achieve better therapeutic effects in particular for drug resistant tumors. Designing a biocompatible delivery system, dual or multiple drugs could addressing these chemotherapy drawbacks and it is the focus of many current biomedical research. METHODS: In the present study, graphene oxide-polyethylene glycol (GOPEG) nanocarrier is designed and loaded with two anticancer drugs; Protocatechuic acid (PCA) and Chlorogenic acid (CA). The designed anticancer nanocomposite was further coated with folic acid to target the cancer cells, as their surface membranes are overexpressed with folate receptors. RESULTS: The particle size distribution of the designed nanocomposite was found to be narrow, 9-40 nm. The release profiles of the loaded drugs; PCA and CA was conducted in human body simulated PBS solutions of pH 7.4 (blood pH) and pH 4.8 (intracellular lysosomal pH). Anticancer properties were evaluated against cancerous cells i.e. liver cancer, HEPG2 and human colon cancer, HT-29 cells. The cytocompatbility was assessed on normal 3T3 fibroblasts cells. CONCLUSION: The size of the final designed anticancer nanocomposite formulation, GOPEG-PCACA-FA was found to be distributed at 9-40 nm with a median of 8 nm. The in vitro release of the drugs PCA and CA was found to be of sustained manner which took more than 100 h for the release. Furthermore, the designed formulation was biocompatible with normal 3T3 cells and showed strong anticancer activity against liver and colon cancer cells.

The Impact of Magnesium-Aluminum-Layered Double Hydroxide-Based Polyvinyl Alcohol Coated on Magnetite on the Preparation of Core-Shell Nanoparticles as a Drug Delivery Agent.

One of the current developments in drug research is the controlled release formulation of drugs, which can be released in a controlled manner at a specific target in the body. Due to the diverse physical and chemical properties of various drugs, a smart drug delivery system is highly sought after. The present study aimed to develop a novel drug delivery system using magnetite nanoparticles as the core and coated with polyvinyl alcohol (PVA), a drug 5-fluorouracil (5FU) and Mg-Al-layered double hydroxide (MLDH) for the formation of FPVA-FU-MLDH nanoparticles. The existence of the coated nanoparticles was supported by various physico-chemical analyses. In addition, the drug content, kinetics, and mechanism of drug release also were studied. 5-fluorouracil (5FU) was found to be released in a controlled manner from the nanoparticles at pH = 4.8 (representing the cancerous cellular environment) and pH = 7.4 (representing the blood environment), governed by pseudo-second-order kinetics. The cytotoxicity study revealed that the anticancer delivery system of FPVA-FU-MLDH nanoparticles showed much better anticancer activity than the free drug, 5FU, against liver cancer and HepG2 cells, and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells.

Increased ROS Scavenging and Antioxidant Efficiency of Chlorogenic Acid Compound Delivered via a Chitosan Nanoparticulate System for Efficient In Vitro Visualization and Accumulation in Human Renal Adenocarcinoma Cells.

Naturally existing Chlorogenic acid (CGA) is an antioxidant-rich compound reported to act a chemopreventive agent by scavenging free radicals and suppressing cancer-causing mechanisms. Conversely, the compound's poor thermal and pH (neutral and basic) stability, poor solubility, and low cellular permeability have been a huge hindrance for it to exhibit its efficacy as a nutraceutical compound. Supposedly, encapsulation of CGA in chitosan nanoparticles (CNP), nano-sized colloidal delivery vector, could possibly assist in enhancing its antioxidant properties, in vitro cellular accumulation, and increase chemopreventive efficacy at a lower concentration. Hence, in this study, a stable, monodispersed, non-toxic CNP synthesized via ionic gelation method at an optimum parameter (600 µL of 0.5 mg/mL of chitosan and 200 µL of 0.7 mg/mL of tripolyphosphate), denoted as CNP°, was used to encapsulate CGA. Sequence of physicochemical analyses and morphological studies were performed to discern the successful formation of the CNP°-CGA hybrid. Antioxidant property (studied via DPPH (1,1-diphenyl-2-picrylhydrazyl) assay), in vitro antiproliferative activity of CNP°-CGA, and in vitro accumulation of fluorescently labeled (FITC) CNP°-CGA in cancer cells were evaluated. Findings revealed that successful formation of CNP°-CGA hybrid was reveled through an increase in particle size 134.44 ± 18.29 nm (polydispersity index (PDI) 0.29 ± 0.03) as compared to empty CNP°, 80.89 ± 5.16 nm (PDI 0.26 ± 0.01) with a maximal of 12.04 µM CGA loaded per unit weight of CNP° using 20 µM of CGA. This result correlated with Fourier-Transform Infrared (FTIR) spectroscopic analysis, transmission Electron Microscopy (TEM) and field emission scanning (FESEM) electron microscopy, and ImageJ evaluation. The scavenging activity of CNP°-CGA (IC50 5.2 ± 0.10 µM) were conserved and slightly higher than CNP° (IC50 6.4±0.78 µM). An enhanced cellular accumulation of fluorescently labeled CNP°-CGA in the human renal cancer cells (786-O) as early as 30 min and increased time-dependently were observed through fluorescent microscopic visualization and flow cytometric assessment. A significant concentration-dependent antiproliferation activity of encapsulated CGA was achieved at IC50 of 16.20 µM as compared to CGA itself (unable to determine from the cell proliferative assay), implying that the competent delivery vector, chitosan nanoparticle, is able to enhance the intracellular accumulation, antiproliferative activity, and antioxidant properties of CGA at lower concentration as compared to CGA alone.

The Acute Effects of Oral Administration of Phytic Acid-Chitosan-Magnetic Iron Oxide Nanoparticles in Mice.

A nanocomposite, phytic acid-chitosan-magnetic iron oxide nanoparticles (IP6-CS-MNPs) has been used to treat colon cancer in vitro, previously. However, its potential toxicity in vivo has yet to be elucidated. Hence, the present study aimed to evaluate the acute effects of oral administration of IP6-CS-MNPs in mice. In this study, 1000 and 2000 mg/kg body weight (b.w) of IP6-CS-MNPs were orally administered to two different groups of BALB/c mice, once. Additionally, the mice in the control group were given only deionized water. After 14 days of post-IP6-CS-MNPs administration, in a similar way to the untreated mice, the treated mice showed no sign of mortality and abnormalities. However, the serum urea level of mice receiving 2000 mg/kg b.w of IP6-CS-MNPs was significantly higher than the control group (p < 0.05). The mice that received 1000 mg/kg IP6-CS-MNPs showed a significantly higher level of serum alkaline phosphatase (ALP) compared to the control group. However, there were no significant histopathological changes seen in the liver and kidneys of treated mice compared to the untreated group.

A Potent Antifungal Agent for Basal Stem Rot Disease Treatment in Oil Palms Based on Chitosan-Dazomet Nanoparticles.

The use of nanotechnology could play a significant role in the agriculture sector, especially in the preparation of new-generation agronanochemicals. Currently, the economically important plant of Malaysia, the oil palm, faces the threat of a devastating disease which is particularly caused by a pathogenic fungus, Ganoderma boninense. For the development of an effective antifungal agent, a series of chitosan nanoparticles loaded with a fumigant, dazomet, were prepared using various concentrations of sodium tripolyphosphate (TPP)-2.5, 5, 10, and 20 mg/mL, abbreviated as CDEN2.5, CDEN5, CDEN10, and CDEN20, respectively. The effect of TPP as a crosslinking agent on the resulting particle size of the synthesized nanoparticles was investigated using a particle size analyzer and high-resolution transmission electron microscopy (HRTEM). Both methods confirmed that increasing the TPP concentration resulted in smaller particles. In addition, in vitro fumigant release at pH 5.5 showed that the release of the fumigant from the nanoparticles was of a sustained manner, with a prolonged release time up to 24 h. Furthermore, the relationship between the chitosan-dazomet nanoparticles and the in vitro antifungal activity against G. boninense was also explored, where the nanoparticles of the smallest size, CDEN20, gave the highest antifungal efficacy with the lowest half maximum effective concentration (EC50) value of 13.7 ± 1.76 ppb. This indicates that the smaller-sized agronanoparticles were more effective as an antifungal agent. The size can be altered, which plays a crucial role in combatting the Ganoderma disease. The agronanoparticles have controlled release properties and high antifungal efficacy on G. boninense, thus making them a promising candidate to be applied in the field for Ganoderma treatment.

Preparation of Chitosan-Hexaconazole Nanoparticles as Fungicide Nanodelivery System for Combating Ganoderma Disease in Oil Palm.

Fungicide is used to control fungal disease by destroying and inhibiting the fungus or fungal spores that cause the disease. However, failure to deliver fungicide to the disease region leads to ineffectiveness in the disease control. Hence, in the present study, nanotechnology has enabled the fungicide active agents (hexaconazole) to be encapsulated into chitosan nanoparticles with the aim of developing a fungicide nanodelivery system that can transport them more effectively to the target cells (Ganoderma fungus). A pathogenic fungus, Ganoderma boninense (G. boninense), is destructive to oil palm whereby it can cause significant loss to oil palm plantations located in the Southeast Asian countries, especially Malaysia and Indonesia. In regard to this matter, a series of chitosan nanoparticles loaded with the fungicide, hexaconazole, was prepared using various concentrations of crosslinking agent sodium tripolyphosphate (TPP). The resulting particle size revealed that the increase of the TPP concentration produced smaller particles. In addition, the in vitro fungicide released at pH 5.5 demonstrated that the fungicide from the nanoparticles was released in a sustainable manner with a prolonged release time up to 86 h. On another note, the in vitro antifungal studies established that smaller particle size leads to lower half maximum effective concentration (EC50) value, which indicates higher antifungal activity against G. boninense.

Graphene Oxide as a Nanocarrier for a Theranostics Delivery System of Protocatechuic Acid and Gadolinium/Gold Nanoparticles.

We have synthesized a graphene oxide (GO)-based theranostic nanodelivery system (GOTS) for magnetic resonance imaging (MRI) using naturally occurring protocatechuic acid (PA) as an anticancer agent and gadolinium (III) nitrate hexahydrate (Gd) as the starting material for a contrast agent,. Gold nanoparticles (AuNPs) were subsequently used as second diagnostic agent. The GO nanosheets were first prepared from graphite via the improved Hummer's protocol. The conjugation of the GO and the PA was done via hydrogen bonding and π-π stacking interactions, followed by surface adsorption of the AuNPs through electrostatic interactions. GAGPA is the name given to the nanocomposite obtained from Gd and PA conjugation. However, after coating with AuNPs, the name was modified to GAGPAu. The physicochemical properties of the GAGPA and GAGPAu nanohybrids were studied using various characterization techniques. The results from the analyses confirmed the formation of the GOTS. The powder X-ray diffraction (PXRD) results showed the diffractive patterns for pure GO nanolayers, which changed after subsequent conjugation of the Gd and PA. The AuNPs patterns were also recorded after surface adsorption. Cytotoxicity and magnetic resonance imaging (MRI) contrast tests were also carried out on the developed GOTS. The GAGPAu was significantly cytotoxic to the human liver hepatocellular carcinoma cell line (HepG2) but nontoxic to the standard fibroblast cell line (3T3). The GAGPAu also appeared to possess higher T1 contrast compared to the pure Gd and water reference. The GOTS has good prospects of serving as future theranostic platform for cancer chemotherapy and diagnosis.

Facile aerobic construction of iron based ferromagnetic nanostructures by a novel microbial nanofactory isolated from tropical freshwater wetlands.

BACKGROUND: Iron based ferromagnetic nanoparticles (IONP) have found a wide range of application in microelectronics, chemotherapeutic cell targeting, and as contrast enhancers in MRI. As such, the design of well-defined monodisperse IONPs is crucial to ensure effectiveness in these applications. Although these nanostructures are currently manufactured using chemical and physical processes, these methods are not environmentally conducive and weigh heavily on energy and outlays. Certain microorganisms have the innate ability to reduce metallic ions in aqueous solution and generate nano-sized IONP's with narrow size distribution. Harnessing this potential is a way forward in constructing microbial nanofactories, capable of churning out high yields of well-defined IONP's with physico-chemical characteristics on par with the synthetically produced ones. RESULTS: In this work, we report the molecular characterization of an actinomycetes, isolated from tropical freshwater wetlands sediments, that demonstrated rapid aerobic extracellular reduction of ferric ions to generate iron based nanoparticles. Characterization of these nanoparticles was carried out using Field Emission Scanning Electron Microscope with energy dispersive X-ray spectroscopy (FESEM-EDX), Field Emission Transmission Electron Microscope (FETEM), Ultraviolet-Visible (UV-Vis) Spectrophotometer, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). This process was carried out at room temperature and humidity and under aerobic conditions and could be developed as an environmental friendly, cost effective bioprocess for the production of IONP's. CONCLUSION: While it is undeniable that iron reducing microorganisms confer a largely untapped resource as potent nanofactories, these bioprocesses are largely anaerobic and hampered by the low reaction rates, highly stringent microbial cultural conditions and polydispersed nanostructures. In this work, the novel isolate demonstrated rapid, aerobic reduction of ferric ions in its extracellular matrix, resulting in IONPs of relatively narrow size distribution which are easily extracted and purified without the need for convoluted procedures. It is therefore hoped that this isolate could be potentially developed as an effective nanofactory in the future.

Nano-Formulation of Ethambutol with Multifunctional Graphene Oxide and Magnetic Nanoparticles Retains Its Anti-Tubercular Activity with Prospects of Improving Chemotherapeutic Efficacy.

Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization's recommended frontline chemotherapy against TB. However, the lengthy treatment regimens consisting of a cocktail of antibiotics affect patient compliance. There is an urgent need to improve the current therapy so as to reduce treatment duration and dosing frequency. In this study, we have designed a novel anti-TB multifunctional formulation by fabricating graphene oxide with iron oxide magnetite nanoparticles serving as a nano-carrier on to which ethambutol was successfully loaded. The designed nanoformulation was characterised using various analytical techniques. The release of ethambutol from anti-TB multifunctional nanoparticles formulation was found to be sustained over a significantly longer period of time in phosphate buffer saline solution at two physiological pH (7.4 and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular activity while remaining non-toxic to the eukaryotic cells tested. The results of this in vitro evaluation of the newly designed nano-formulation endorse its further development in vivo.

Novel Anti-Tuberculosis Nanodelivery Formulation of Ethambutol with Graphene Oxide.

Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients' noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB.

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

PURPOSE: In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. METHODS: First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. RESULTS: TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (P<0.05). CONCLUSIONS: The findings of this study suggest that TAT-conjugated PAMAM dendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Biocompatible polymers coated on carboxylated nanotubes functionalized with betulinic acid for effective drug delivery.

Chemically functionalized carbon nanotubes are highly suitable and promising materials for potential biomedical applications like drug delivery due to their distinct physico-chemical characteristics and unique architecture. However, they are often associated with problems like insoluble in physiological environment and cytotoxicity issue due to impurities and catalyst residues contained in the nanotubes. On the other hand, surface coating agents play an essential role in preventing the nanoparticles from excessive agglomeration as well as providing good water dispersibility by replacing the hydrophobic surfaces of nanoparticles with hydrophilic moieties. Therefore, we have prepared four types of biopolymer-coated single walled carbon nanotubes systems functionalized with anticancer drug, betulinic acid in the presence of Tween 20, Tween 80, polyethylene glycol and chitosan as a comparative study. The Fourier transform infrared spectroscopy studies confirm the bonding of the coating molecules with the SWBA and these results were further supported by Raman spectroscopy. All chemically coated samples were found to release the drug in a slow, sustained and prolonged fashion compared to the uncoated ones, with the best fit to pseudo-second order kinetic model. The cytotoxic effects of the synthesized samples were evaluated in mouse embryonic fibroblast cells (3T3) at 24, 48 and 72 h. The in vitro results reveal that the cytotoxicity of the samples were dependent upon the drug release profiles as well as the chemical components of the surface coating agents. In general, the initial burst, drug release pattern and cytotoxicity could be well-controlled by carefully selecting the desired materials to suit different therapeutic applications.

Preparation of Tween 80-Zn/Al-levodopa-layered double hydroxides nanocomposite for drug delivery system.

We incorporated anti-Parkinsonian drug, levodopa (dopa), in Zn/Al-LDH by coprecipitation method to form dopa-LDH nanocomposite. Further coating of Tween-80 on the external surfaces of dopa-LDH nanocomposite was achieved through the oxygen of C=O group of Tween-80 with the layer of dopa-LDH nanocomposite. The final product is called Tween-dopa-LDH nanocomposite. The X-ray diffraction indicates that the Tween-dopa-LDH nanocomposite was formed by aggregation structure. From the TGA data, the Tween-80 loading on the surface of LDH and dopa-LDH was 8.6 and 7.4%, respectively. The effect of coating process on the dopa release from Tween-dopa-LDH nanocomposite was also studied. The release from Tween-dopa-LDH nanocomposite shows slower release compared to the release of the drug from dopa-LDH nanocomposite as done previously in our study, presumably due to the retarding shielding effect. The cell viability study using PC12 showed improved viability with Tween-80 coating on dopa-LDH nanocomposite as studied by mitochondrial dehydrogenase activity (MTT assay).

Development of a highly biocompatible antituberculosis nanodelivery formulation based on para-aminosalicylic acid-zinc layered hydroxide nanocomposites.

Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 µg/mL compared to the free drug PAS with a MIC of 5.0 µg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies.