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.

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).

In vitro sustained release study of gallic acid coated with magnetite-PEG and magnetite-PVA for drug delivery system.

The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.

Release behavior and toxicity profiles towards leukemia (WEHI-3B) cell lines of 6-mercaptopurine-PEG-coated magnetite nanoparticles delivery system.

The coating of an active drug, 6-mercaptopurine, into the iron oxide nanoparticles-polyethylene glycol (FNPs-PEG) in order to form a new nanocomposite, FPEGMP-2, was accomplished using coprecipitation technique. The resulting nanosized with a narrow size distribution magnetic polymeric particles show the superparamagnetic properties with 38.6 emu/g saturation magnetization at room temperature. Fourier transform infrared spectroscopy and the thermal analysis study supported the formation of the nanocomposite and the enhancement of thermal stability in the resulting nanocomposite comparing with its counterpart in free state. The loading of 6-mercaptopurine (MP) in the FPEGMP-2 nanocomposite was estimated to be about 5.6% and the kinetic experimental data properly correlated with the pseudo-second order model. Also, the release of MP from the FPEGMP-2 nanocomposite shows the sustained release manner which is remarkably lower in phosphate buffered solution at pH 7.4 than pH 4.8, due to different release mechanism. The maximum percentage release of MP from the nanocomposite reached about 60% and 97% within about 92 and 74 hours when exposed to pH 7.4 and 4.8, respectively.

Toxicity and metabolism of layered double hydroxide intercalated with levodopa in a Parkinson's disease model.

Layered hydroxide nanoparticles are generally biocompatible, and less toxic than most inorganic nanoparticles, making them an acceptable alternative drug delivery system. Due to growing concern over animal welfare and the expense of in vivo experiments both the public and the government are interested to find alternatives to animal testing. The toxicity potential of zinc aluminum layered hydroxide (ZAL) nanocomposite containing anti-Parkinsonian agent may be determined using a PC 12 cell model. ZAL nanocomposite demonstrated a decreased cytotoxic effect when compared to levodopa on PC12 cells with more than 80% cell viability at 100 µg/mL compared to less than 20% cell viability in a direct levodopa exposure. Neither levodopa-loaded nanocomposite nor the un-intercalated nanocomposite disturbed the cytoskeletal structure of the neurogenic cells at their IC50 concentration. Levodopa metabolite (HVA) released from the nanocomposite demonstrated the slow sustained and controlled release character of layered hydroxide nanoparticles unlike the burst uptake and release system shown with pure levodopa treatment.

Sustained release of prindopril erbumine from its chitosan-coated magnetic nanoparticles for biomedical applications.

The preparation of magnetic nanoparticles coated with chitosan-prindopril erbumine was accomplished and confirmed by X-ray diffraction, TEM, magnetic measurements, thermal analysis and infrared spectroscopic studies. X-ray diffraction and TEM results demonstrated that the magnetic nanoparticles were pure iron oxide phase, having a spherical shape with a mean diameter of 6 nm, compared to 15 nm after coating with chitosan-prindopril erbumine (FCPE). Fourier transform infrared spectroscopy study shows that the coating of iron oxide nanoparticles takes place due to the presence of some bands that were emerging after the coating process, which belong to the prindopril erbumine (PE). The thermal stability of the PE in an FCPE nanocomposite was remarkably enhanced. The release study showed that around 89% of PE could be released within about 93 hours by a phosphate buffer solution at pH 7.4, which was found to be of sustained manner governed by first order kinetic. Compared to the control (untreated), cell viability study in 3T3 cells at 72 h post exposure to both the nanoparticles and the pure drug was found to be sustained above 80% using different doses.

Effect of protocatechuic acid-layered double hydroxide nanoparticles on diethylnitrosamine/phenobarbital-induced hepatocellular carcinoma in mice.

Researchers investigating cancer chemotherapy and management continue to search for agents that selectively kill malignant cells and leave healthy neighboring cells intact. Natural products provide relevant resources for anti-cancer drug discovery. However, the physicochemical properties of these compounds limit their efficient uptake and bioavailability. We introduced a nanocarrier system, namely, zinc-aluminum-layered double hydroxide (ZnAl-LDH) intercalated with protocatechuic acid. In this study, the efficacy and toxicity of protocatechuic acid intercalated in zinc aluminum-layered double hydroxide nanoparticles (PCA-ZnAl) against diethylnitrosamine/phenobarbital (DEN/PB)-induced hepatocellular carcinoma (HCC) in BALB/c mice was evaluated. HCC in male mice was induced by a single-dose intraperitoneal administration of DEN and was promoted by the introduction of PB via drinking water for 12 weeks. HCC induction was confirmed after the DEN/PB introduction period by measurement of the elevated level of serum α-feto protein (AFP). The results showed that the level of α-fetoprotein was significantly reduced in PCA-ZnAl (350±43.90 ng/mL), doxorubicin (DOX) (290±20.52 ng/mL) and ZnAl-LDH (390±19.65 ng/mL) treated animals compared to HCC mice treated with normal saline (580.4± 52.04 ng/mL). Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were significantly increased, whereas the level of lipid peroxidation was significantly decreased in HCC mice treated with DOX, PCA-ZnAl and ZnAl-LDH compared with those in HCC mice treated with saline. Restoration of hepatocyte morphology was observed following treatment that was comparable to that in the normal control group. Deterioration of hepatic cells and a significant increase of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were observed in the cancer-induced untreated group compared with that in the groups treated with nanoparticles. The histopathological features of the liver obtained from PCA-ZnAl-treated mice showed a uniform size with a similar distribution of the nuclear-cytoplasmic ratio and nucleus centrally located in the cytoplasm, similar to the normal liver cells. The results underscored the potential of PCA-ZnAl for the treatment of hepatocellular carcinoma.

Incorporation of Levodopa into Biopolymer Coatings Based on Carboxylated Carbon Nanotubes for pH-Dependent Sustained Release Drug Delivery.

Four drug delivery systems were formulated by non-covalent functionalization of carboxylated single walled carbon nanotubes using biocompatible polymers as coating agent (i.e., Tween 20, Tween 80, chitosan or polyethylene glycol) for the delivery of levodopa, a drug used in Parkinson's disease. The chemical interaction between the coating agent and carbon nanotubes-levodopa conjugate was confirmed by Fourier transform infrared (FTIR) and Raman studies. The drug release profiles were revealed to be dependent upon the type of applied coating material and this could be further adjusted to a desired rate to meet different biomedical conditions. In vitro drug release experiments measured using UV-Vis spectrometry demonstrated that the coated conjugates yielded a more prolonged and sustained release pattern compared to the uncoated conjugate. Cytotoxicity of the formulated conjugates was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using normal mouse embryonic fibroblast 3T3 cell line. Compared to the non-coated conjugate, the MTT data indicated that the coating procedure improved the biocompatibility of all systems by 34⁻41% when the concentration used exceeded 100 µg/mL. In conclusion, the comprehensive results of this study suggest that carbon nanotubes-based drug carrier coated with a suitable biomaterial may possibly be a potential nanoparticle system that could facilitate drug delivery to the brain with tunable physicochemical properties.

Evaluation of in vitro efficacy of docetaxel-loaded calcium carbonate aragonite nanoparticles (DTX-CaCO3NP) on 4T1 mouse breast cancer cell line.

Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5 µg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p < 0.05) number of apoptotic cells in both free DTX and DTX-CaCO3NP groups. Cell cycle analysis showed cycle arrest at subG0 and G2/M phases in both treatment groups. SEM showed presence of cellular blebbing, while TEM showed nuclear fragmentation, apoptosis, and vacuolation in the treatment groups. Scratch assay showed lower (p < 0.05) closure in both free DTX and DTX-CaCO3NP groups. The results from this study showed that DTX-CaCO3NP has similar anticancer effects on 4T1 cells as free DTX, and since it has a slow release rate, it is a more preferred substitute for free DTX.

The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model.

N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO) is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p) and after an hour, these groups were administered with saline (10 mL/kg), silymarin-positive control (100 mg/kg of bw, i.p), MO leaf extract (100 mg/kg of bw, i.p), and MO leaf extract (200 mg/kg bw, i.p) respectively. Group 1 was administered saline (10 mL/kg) during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) and decreased anti-inflammatory (IL-10) cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract treatment. Therefore, MO leaf extract has demonstrated some therapeutic effectiveness against APAP-induced nephrotoxicity through enhancement of the endogenous antioxidant system and a modulatory effect on specific inflammatory cytokines in kidney tissues.

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique.

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis - bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA-phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of -39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.

Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis.

A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs) with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs) were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4) with the highest drug-loading efficiency (54.05%) was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from -19.4±3.3 to -21.2±5.7 mV after vancomycin loading. VANP displayed 120 hours (5 days) release profile of vancomycin that exhibited high antibacterial effect against methicillin-resistant Staphylococcus aureus ATCC 29213. The cell proliferation assay showed 80% cell viability of human fetal osteoblast cell line 1.19 treated with the highest concentration of VANP (250 µg/mL), indicating good biocompatibility of VANP. In summary, VANP is a potential formulation for the development of an LADS against osteomyelitis with optimal antibacterial efficacy, good bone resorbability, and biocompatibility.

Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite.

Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

Nanotechnology in drug delivery: the need for more cell culture based studies in screening.

Advances in biomedical science are leading to upsurge synthesis of nanodelivery systems for drug delivery. The systems were characterized by controlled, targeted and sustained drug delivery ability. Humans are the target of these systems, hence, animals whose systems resembles humans were used to predict outcome. Thus, increasing costs in money and time, plus ethical concerns over animal usage. However, with consideration and planning in experimental conditions, in vitro pharmacological studies of the nanodelivery can mimic the in vivo system. This can function as a simple method to investigate the effect of such materials without endangering animals especially at screening phase.

Layered double hydroxide nanocomposite for drug delivery systems; bio-distribution, toxicity and drug activity enhancement.

The production of layered double hydroxide(LDH) nanocomposite as an alternative drug delivery system against various ailments is on the increase. Their toxicity potential is usually dose and time dependent with particle sizes, shapes and surface charge playing some role both in the in vitro and in vivo studies. The reticular endothelial system of especially the liver and spleen were shown to sequestrate most of these nanocomposite, especially those with sizes greater than 50 nm. The intracellular drug delivery by these particles is mainly via endocytotic pathways aided by the surface charges in most cases. However, structural modification of these nanocomposite via coating using different types of material may lower the toxicity where present. More importantly, the coating may serve as targeting ligand hence, directing drug distribution and leading to proper drug delivery to specific area of need; it equally decreases the unwanted nanocomposite accumulation in especially the liver and spleen. These nanocomposite have the advantage of wider bio-distribution irrespective of route of administration, excellent targeted delivery potential with ease of synthetic modification including coating.

Antimicrobial and controlled release studies of a novel nystatin conjugated iron oxide nanocomposite.

Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. In the present study, we prepared a nystatin nanocomposite (Nyst-CS-MNP) by loading nystatin (Nyst) on chitosan (CS) coated magnetic nanoparticles (MNPs). The magnetic nanocomposites were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), vibrating sample magnetometer (VSM), and scanning electron microscopy (SEM). The XRD results showed that the MNPs and nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9% loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS-MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated using an agar diffusion method and showed enhanced antifungal activity against Candida albicans. In this manner, this study introduces a novel nanocomposite that can decrease fungus activity on-demand for numerous medical applications.

Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study.

Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

Development of a controlled-release anti-parkinsonian nanodelivery system using levodopa as the active agent.

A new layered organic-inorganic nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl) alanine (levodopa), intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH) was synthesized using a direct coprecipitation method. The resulting nanocomposite was composed of the organic moiety, levodopa, sandwiched between Zn/Al-LDH inorganic interlayers. The basal spacing of the resulting nano-composite was 10.9 Å. The estimated loading of levodopa in the nanocomposite was approximately 16% (w/w). A Fourier transform infrared study showed that the absorption bands of the nanocomposite were characteristic of both levodopa and Zn/Al-LDH, which further confirmed intercalation, and that the intercalated organic moiety in the nanocomposite was more thermally stable than free levodopa. The resulting nanocomposite showed sustained-release properties, so can be used in a controlled-release formulation. Cytotoxicity analysis using an MTT assay also showed increased cell viability of 3T3 cells exposed to the newly synthesized nanocomposite compared with those exposed to pure levodopa after 72 hours of exposure.

Preparation and characterization of 6-mercaptopurine-coated magnetite nanoparticles as a drug delivery system.

BACKGROUND: Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. METHODS AND RESULTS: We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe3O4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe3O4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe3O4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate "burst release" and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. CONCLUSION: Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue.

Preparation of Fe3O4 magnetic nanoparticles coated with gallic acid for drug delivery.

BACKGROUND AND METHODS: Magnetic iron oxide nanoparticles were prepared using a sonochemical method under atmospheric conditions at a Fe²âº to Fe³âº molar ratio of 1:2. The iron oxide nanoparticles were subsequently coated with chitosan and gallic acid to produce a core-shell structure. RESULTS: X-ray diffraction demonstrated that the magnetic nanoparticles were pure Fe3O4 with a cubic inverse spinel structure. Transmission electron microscopy showed that the Fe3O4 nanoparticles were of spherical shape with a mean diameter of 11 nm, compared with 13 nm for the iron oxide-chitosan-gallic acid (FCG) nanocarriers. CONCLUSION: The magnetic nanocarrier enhanced the thermal stability of the drug, gallic acid. Release of the active drug from the FCG nanocarrier was found to occur in a controlled manner. The gallic acid and FCG nanoparticles were not toxic in a normal human fibroblast (3T3) line, and anticancer activity was higher in HT29 than MCF7 cell lines.