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

Kura AU, Hussein-Al-Ali SH, Hussein MZ, Fakurazi S

ScientificWorldJournal, 2014;2014:104246.
PMID: 24782658 DOI: 10.1155/2014/104246

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).
Fulltext Controlled-release approaches towards the chemotherapy of tuberculosis

Saifullah B, Hussein MZ, Hussein Al Ali SH

Int J Nanomedicine, 2012;7:5451-63.
PMID: 23091386 DOI: 10.2147/IJN.S34996

Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization's 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18-24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs) seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages.
Fulltext Chlorambucil-Iron Oxide Nanoparticles as a Drug Delivery System for Leukemia Cancer Cells

Hussein-Al-Ali SH, Hussein MZ, Bullo S, Arulselvan P

Int J Nanomedicine, 2021;16:6205-6216.
PMID: 34526768 DOI: 10.2147/IJN.S312752

Introduction: Traditional cancer therapies may have incomplete eradication of cancer or destroy the normal cells. Nanotechnology solves the demerit by a guide in surgical resection of tumors, targeted chemotherapies, selective to cancerous cells, etc. This new technology can reduce the risk to the patient and automatically increased the probability of survival. Toward this goal, novel iron oxide nanoparticles (IONPs) coupled with leukemia anti-cancer drug were prepared and assessed.
Methods: The IONPs were prepared by the co-precipitation method using Fe+3/Fe+2ratio of 2:1. These IONPs were used as a carrier for chlorambucil (Chloramb), where the IONPs serve as the cores and chitosan (CS) as a polymeric shell to form Chloramb-CS-IONPs. The products were characterized using transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) analysis, Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM) analyses, and thermal gravimetric analysis (TGA).
Results: The as-prepared IONPs were found to be magnetite (Fe3O4) and were coated by the CS polymer/Chloramb drug for the formation of the Chloramb-CS-IONPs. The average size for CS-IONPs and Chloramb-CS-IONPs nanocomposite was found to be 15 nm, with a drug loading of 19% for the letter. The release of the drug from the nanocomposite was found to be of a controlled-release manner with around 89.9% of the drug was released within about 5000 min and governed by the pseudo-second order. The in vitro cytotoxicity studies of CS-IONPs and Chloramb-CS-IONPs nanocomposite were tested on the normal fibroblast cell lines (3T3) and leukemia cancer cell lines (WEHI). Chloramb in Chloramb-CS-IONPs nanocomposite was found to be more efficient compared to its free form.
Conclusion: This work shows that Chloramb-CS-IONPs nanocomposite is a promising candidate for magnetically targeted drug delivery for leukemia anti-cancer agents.
Fulltext Synthesis, characterization, and antimicrobial activity of an ampicillin-conjugated magnetic nanoantibiotic for medical applications

Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Geilich BM, Webster TJ

Int J Nanomedicine, 2014;9:3801-14.
PMID: 25143729 DOI: 10.2147/IJN.S61143

Because of their magnetic properties, magnetic nanoparticles (MNPs) have numerous diverse biomedical applications. In addition, because of their ability to penetrate bacteria and biofilms, nanoantimicrobial agents have become increasingly popular for the control of infectious diseases. Here, MNPs were prepared through an iron salt coprecipitation method in an alkaline medium, followed by a chitosan coating step (CS-coated MNPs); finally, the MNPs were loaded with ampicillin (amp) to form an amp-CS-MNP nanocomposite. Both the MNPs and amp-CS-MNPs were subsequently characterized and evaluated for their antibacterial activity. X-ray diffraction results showed that the MNPs and nanocomposites were composed of pure magnetite. Fourier transform infrared spectra and thermogravimetric data for the MNPs, CS-coated MNPs, and amp-CS-MNP nanocomposite were compared, which confirmed the CS coating on the MNPs and the amp-loaded nanocomposite. Magnetization curves showed that both the MNPs and the amp-CS-MNP nanocomposites were superparamagnetic, with saturation magnetizations at 80.1 and 26.6 emu g(-1), respectively. Amp was loaded at 8.3%. Drug release was also studied, and the total release equilibrium for amp from the amp-CS-MNPs was 100% over 400 minutes. In addition, the antimicrobial activity of the amp-CS-MNP nanocomposite was determined using agar diffusion and growth inhibition assays against Gram-positive bacteria and Gram-negative bacteria, as well as Candida albicans. The minimum inhibitory concentration of the amp-CS-MNP nanocomposite was determined against bacteria including Mycobacterium tuberculosis. The synthesized nanocomposites exhibited antibacterial and antifungal properties, as well as antimycobacterial effects. Thus, this study introduces a novel β-lactam antibacterial-based nanocomposite that can decrease fungus activity on demand for numerous medical applications.
Fulltext Toxicity and metabolism of layered double hydroxide intercalated with levodopa in a Parkinson's disease model

Kura AU, Ain NM, Hussein MZ, Fakurazi S, Hussein-Al-Ali SH

Int J Mol Sci, 2014;15(4):5916-27.
PMID: 24722565 DOI: 10.3390/ijms15045916

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.
Fulltext Antituberculosis nanodelivery system with controlled-release properties based on para-amino salicylate-zinc aluminum-layered double-hydroxide nanocomposites

Saifullah B, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S

Drug Des Devel Ther, 2013;7:1365-75.
PMID: 24255593 DOI: 10.2147/DDDT.S50665

We report the intercalation and characterization of para-amino salicylic acid (PASA) into zinc/aluminum-layered double hydroxides (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). Powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis revealed that the PASA drugs were accommodated within the ZLDH interlayers. The anions of the drug were accommodated as an alternate monolayer (along the long-axis orientation) between ZLDH interlayers. Drug loading was estimated to be 22.8% and 16.6% for PASA-D and PASA-I, respectively. The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH 7.4 and 4.8. The release followed the pseudo-second-order model for both nanocomposites. Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assays) was assessed against normal human lung fibroblast MRC-5 and 3T3 mouse fibroblast cells at 24, 48, and 72 hours. The results showed that the nanocomposite formulations did not possess any cytotoxicity, at least up to 72 hours.
Fulltext Novel kojic acid-polymer-based magnetic nanocomposites for medical applications

Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Ismail M, Dorniani D, Webster TJ

Int J Nanomedicine, 2014;9:351-62.
PMID: 24453486 DOI: 10.2147/IJN.S53847

Iron oxide magnetic nanoparticles (MNPs) were synthesized by the coprecipitation of iron salts in sodium hydroxide followed by coating separately with chitosan (CS) and polyethylene glycol (PEG) to form CS-MNPs and PEG-MNPs nanoparticles, respectively. They were then loaded with kojic acid (KA), a pharmacologically bioactive natural compound, to form KA-CS-MNPs and KA-PEG-MNPs nanocomposites, respectively. The MNPs and their nanocomposites were characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, vibrating sample magnetometry, and scanning electron microscopy. The powder X-ray diffraction data suggest that all formulations consisted of highly crystalline, pure magnetite Fe3O4. The Fourier transform infrared spectroscopy and thermogravimetric analysis confirmed the presence of both polymers and KA in the nanocomposites. Magnetization curves showed that both nanocomposites (KA-CS-MNPs and KA-PEG-MNPs) were superparamagnetic with saturation magnetizations of 8.1 emu/g and 26.4 emu/g, respectively. The KA drug loading was estimated using ultraviolet-visible spectroscopy, which gave a loading of 12.2% and 8.3% for the KA-CS-MNPs and KA-PEG-MNPs nanocomposites, respectively. The release profile of the KA from the nanocomposites followed a pseudo second-order kinetic model. The agar diffusion test was performed to evaluate the antimicrobial activity for both KA-CS-MNPs and KA-PEG-MNPs nanocomposites against a number of microorganisms using two Gram-positive (methicillin-resistant Staphylococcus aureus and Bacillus subtilis) and one Gram-negative (Salmonella enterica) species, and showed some antibacterial activity, which could be enhanced in future studies by optimizing drug loading. This study provided evidence for the promise for the further investigation of the possible beneficial biological activities of KA and both KA-CS-MNPs and KA-PEG-MNPs nanocomposites in nanopharmaceutical applications.
Arginine-chitosan- and arginine-polyethylene glycol-conjugated superparamagnetic nanoparticles: Preparation, cytotoxicity and controlled-release

Hussein-Al-Ali SH, Arulselvan P, Fakurazi S, Hussein MZ, Dorniani D

J Biomater Appl, 2014 Jan 19;29(2):186-198.
PMID: 24445774

Iron oxide magnetic nanoparticles (MNPs) can be used in targeted drug delivery systems for localized cancer treatment. MNPs coated with biocompatible polymers are useful for delivering anticancer drugs. Iron oxide MNPs were synthesized via co-precipitation method then coated with either chitosan (CS) or polyethylene glycol (PEG) to form CS-MNPs and PEG-MNPs, respectively. Arginine (Arg) was loaded onto both coated nanoparticles to form Arg-CS-MNP and Arg-PEG-MNP nanocomposites. The X-ray diffraction results for the MNPs and the Arg-CS-MNP and Arg-PEG-MNPs nanocomposites indicated that the iron oxide contained pure magnetite. The amount of CS and PEG bound to the MNPs were estimated via thermogravimetric analysis and confirmed via Fourier transform infrared spectroscopy analysis. Arg loading was estimated using UV-vis measurements, which yielded values of 5.5% and 11% for the Arg-CS-MNP and Arg-PEG-MNP nanocomposites, respectively. The release profile of Arg from the nanocomposites followed a pseudo-second-order kinetic model. The cytotoxic effects of the MNPs, Arg-CS-MNPs, and Arg-PEG-MNPs were evaluated in human cervical carcinoma cells (HeLa), mouse embryonic fibroblast cells (3T3) and breast adenocarcinoma cells (MCF-7). The results indicate that the MNPs, Arg-CS-MNPs, and Arg-PEG-MNPs do not exhibit cytotoxicity toward 3T3 and HeLa cells. However, treatment of the MCF-7 cells with the Arg-CS-MNP and Arg-PEG-MNP nanocomposites reduced the cancer cell viability with IC50 values of 48.6 and 42.6 µg/mL, respectively, whereas the MNPs and free Arg did not affect the viability of the MCF-7 cells.
Fulltext Development of a controlled-release anti-parkinsonian nanodelivery system using levodopa as the active agent

Kura AU, Hussein Al Ali SH, Hussein MZ, Fakurazi S, Arulselvan P

Int J Nanomedicine, 2013;8:1103-10.
PMID: 23524513 DOI: 10.2147/IJN.S39740

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.
Fulltext Preparation and controlled-release studies of a protocatechuic acid-magnesium/aluminum-layered double hydroxide nanocomposite

Barahuie F, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S, Zainal Z

Int J Nanomedicine, 2013;8:1975-87.
PMID: 23737666 DOI: 10.2147/IJN.S42718

In the study reported here, magnesium/aluminum (Mg/Al)-layered double hydroxide (LDH) was intercalated with an anticancer drug, protocatechuic acid, using ion-exchange and direct coprecipitation methods, with the resultant products labeled according to the method used to produce them: "PANE" (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the ion-exchange method) and "PAND" (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the direct method), respectively. Powder X-ray diffraction and Fourier transform infrared spectroscopy confirmed the intercalation of protocatechuic acid into the inter-galleries of Mg/Al-LDH. The protocatechuic acid between the interlayers of PANE and PAND was found to be a monolayer, with an angle from the z-axis of 8° for PANE and 15° for PAND. Thermogravimetric and differential thermogravimetric analysis results revealed that the thermal stability of protocatechuic acid was markedly enhanced upon intercalation. The loading of protocatechuic acid in PANE and PAND was estimated to be about 24.5% and 27.5% (w/w), respectively. The in vitro release study of protocatechuic acid from PANE and PAND in phosphate-buffered saline at pH 7.4, 5.3, and 4.8 revealed that the nanocomposites had a sustained release property. After 72 hours incubation of PANE and PAND with MCF-7 human breast cancer and HeLa human cervical cancer cell lines, it was found that the nanocomposites had suppressed the growth of these cancer cells, with a half maximal inhibitory concentration of 35.6 μg/mL for PANE and 36.0 μg/mL for PAND for MCF-7 cells, and 19.8 μg/mL for PANE and 30.3 μg/mL for PAND for HeLa cells. No half maximal inhibitory concentration for either nanocomposite was found for 3T3 cells.
Fulltext Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

Saifullah B, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S

Chem Cent J, 2013;7(1):72.
PMID: 23601852 DOI: 10.1186/1752-153X-7-72

Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB.
Fulltext Controlled release and angiotensin-converting enzyme inhibition properties of an antihypertensive drug based on a perindopril erbumine-layered double hydroxide nanocomposite

Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN

Int J Nanomedicine, 2012;7:2129-41.
PMID: 22619549 DOI: 10.2147/IJN.S30461

The intercalation of perindopril erbumine into Zn/Al-NO(3)-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.
Fulltext In vitro inhibition of histamine release behavior of cetirizine intercalated into Zn/Al- and Mg/Al-layered double hydroxides

Hussein-Al-Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN

Int J Mol Sci, 2012;13(5):5899-916.
PMID: 22754339 DOI: 10.3390/ijms13055899

The intercalation of cetirizine into two types of layered double hydroxides, Zn/Al and Mg/Al, has been investigated by the ion exchange method to form CTZAN and CTMAN nanocomposites, respectively. The basal spacing of the nanocomposites were expanded to 31.9 Å for CTZAN and 31.2 Å for CTMAN, suggesting that cetirizine anion was intercalated into Layered double hydroxides (LDHs) and arranged in a tilted bilayer fashion. A Fourier transform infrared spectroscopy (FTIR) study supported the formation of both the nanocomposites, and the intercalated cetirizine is thermally more stable than its counterpart in free state. The loading of cetirizine in the nanocomposite was estimated to be about 57.2% for CTZAN and 60.7% CTMAN. The cetirizine release from the nanocomposites show sustained release manner and the release rate of cetirizine from CTZAN and CTMAN nanocomposites at pH 7.4 is remarkably lower than that at pH 4.8, presumably due to the different release mechanism. The inhibition of histamine release from RBL2H3 cells by the free cetirizine is higher than the intercalated cetirizine both in CTZAN and CTMAN nanocomposites. The viability in human Chang liver cells at 1000 μg/mL for CTZAN and CTMAN nanocomposites are 74.5 and 91.9%, respectively.
Fulltext Comparative study of Mg/Al- and Zn/Al-layered double hydroxide-perindopril erbumine nanocomposites for inhibition of angiotensin-converting enzyme

Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN

Int J Nanomedicine, 2012;7:4251-62.
PMID: 22904631 DOI: 10.2147/IJN.S32267

The intercalation of a drug active, perindopril, into Mg/Al-layered double hydroxide for the formation of a new nanocomposite, PMAE, was accomplished using a simple ion exchange technique. A relatively high loading percentage of perindopril of about 36.5% (w/w) indicates that intercalation of the active took place in the Mg/Al inorganic interlayer. Intercalation was further supported by Fourier transform infrared spectroscopy, and thermal analysis shows markedly enhanced thermal stability of the active. The release of perindopril from the nanocomposite occurred in a controlled manner governed by pseudo-second order kinetics. MTT assay showed no cytotoxicity effects from either Mg/Al-layered double hydroxide or its nanocomposite, PMAE. Mg/Al-layered double hydroxide showed angiotensin-converting enzyme inhibitory activity, with 5.6% inhibition after 90 minutes of incubation. On incubation of angiotensin-converting enzyme with 0.5 μg/mL of the PMAE nanocomposite, inhibition of the enzyme increased from 56.6% to 70.6% at 30 and 90 minutes, respectively. These results are comparable with data reported in the literature for Zn/Al-perindopril.
Fulltext Preparation of hippurate-zinc layered hydroxide nanohybrid and its synergistic effect with tamoxifen on HepG2 cell lines

Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Zainal Z, Hakim MN

Int J Nanomedicine, 2011;6:3099-111.
PMID: 22163163 DOI: 10.2147/IJN.S24510

A new simple preparation method for a hippurate-intercalated zinc-layered hydroxide (ZLH) nanohybrid has been established, which does not need an anion-exchange procedure to intercalate the hippurate anion into ZLH interlayers.
Fulltext Hippuric acid nanocomposite enhances doxorubicin and oxaliplatin-induced cytotoxicity in MDA-MB231, MCF-7 and Caco2 cell lines

Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Bullo S

Drug Des Devel Ther, 2013;7:25-31.
PMID: 23345969 DOI: 10.2147/DDDT.S37070

The aim of the current study is to design a new nanocomposite for inducing cytotoxicity of doxorubicin and oxaliplatin toward MDA-MB231, MCF-7, and Caco2 cell lines. A hippuric acid (HA) zinc layered hydroxide (ZLH) nanocomposite was synthesized under an aqueous environment using HA and zinc oxide (ZnO) as the precursors.
Fulltext The ability of streptomycin-loaded chitosan-coated magnetic nanocomposites to possess antimicrobial and antituberculosis activities

El Zowalaty ME, Hussein Al Ali SH, Husseiny MI, Geilich BM, Webster TJ, Hussein MZ

Int J Nanomedicine, 2015;10:3269-74.
PMID: 25995633 DOI: 10.2147/IJN.S74469

Magnetic nanoparticles (MNPs) were synthesized by the coprecipitation of Fe(2+) and Fe(3+) iron salts in alkali media. MNPs were coated by chitosan (CS) to produce CS-MNPs. Streptomycin (Strep) was loaded onto the surface of CS-MNPs to form a Strep-CS-MNP nanocomposite. MNPs, CS-MNPs, and the nanocomposites were subsequently characterized using X-ray diffraction and were evaluated for their antibacterial activity. The antimicrobial activity of the as-synthesized nanoparticles was evaluated using different Gram-positive and Gram-negative bacteria, as well as Mycobacterium tuberculosis. For the first time, it was found that the nanoparticles showed antimicrobial activities against the tested microorganisms (albeit with a more pronounced effect against Gram-negative than Gram-positive bacteria), and thus, should be further studied as a novel nano-antibiotic for numerous antimicrobial and antituberculosis applications. Moreover, since these nanoparticle bacteria fighters are magnetic, one can easily envision magnetic field direction of these nanoparticles to fight unwanted microorganism presence on demand. Due to the ability of magnetic nanoparticles to increase the sensitivity of imaging modalities (such as magnetic resonance imaging), these novel nanoparticles can also be used to diagnose the presence of such microorganisms. In summary, although requiring further investigation, this study introduces for the first time a new type of magnetic nanoparticle with microorganism theranostic properties as a potential tool to both diagnose and treat diverse microbial and tuberculosis infections.
Fulltext A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design

Sabbagh HAK, Hussein-Al-Ali SH, Hussein MZ, Abudayeh Z, Ayoub R, Abudoleh SM

Polymers (Basel), 2020 Apr 01;12(4).
PMID: 32244671 DOI: 10.3390/polym12040772

The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl2 concentrations, whereas zeta potential depends only on the Alg and CaCl2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (-9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm-1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model (R2 between 0.956-0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.
Fulltext In vitro delivery and controlled release of Doxorubicin for targeting osteosarcoma bone cancer

Kamba SA, Ismail M, Hussein-Al-Ali SH, Ibrahim TA, Zakaria ZA

Molecules, 2013 Aug 30;18(9):10580-98.
PMID: 23999729 DOI: 10.3390/molecules180910580

Drug delivery systems are designed to achieve drug therapeutic index and enhance the efficacy of controlled drug release targeting with specificity and selectivity by successful delivery of therapeutic agents at the desired sites without affecting the non-diseased neighbouring cells or tissues. In this research, we developed and demonstrated a bio-based calcium carbonate nanocrystals carrier that can be loaded with anticancer drug and selectively deliver it to cancer cells with high specificity by achieving the effective osteosarcoma cancer cell death without inducing specific toxicity. The results showed pH sensitivity of the controlled release characteristics of the drug at normal physiological pH 7.4 with approximately 80% released within 1,200 min but when exposed pH 4.8 the corresponding 80% was released in 50 min. This study showed that the DOX-loaded CaCO₃ nanocrystals have promising applications in delivery of anticancer drugs.
Fulltext Synthesis, characterization, controlled release, and antibacterial studies of a novel streptomycin chitosan magnetic nanoantibiotic

Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Ismail M, Webster TJ

Int J Nanomedicine, 2014;9:549-57.
PMID: 24549109 DOI: 10.2147/IJN.S53079

This study describes the preparation, characterization, and controlled release of a streptomycin-chitosan-magnetic nanoparticle-based antibiotic in an effort to improve the treatment of bacterial infections. Specifically, chitosan-magnetic nanoparticles were synthesized by an incorporation method and were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and vibrating sample magnetometry. Streptomycin was incorporated into the nanoparticles to form a streptomycin-coated chitosan-magnetic nanoparticle (Strep-CS-MNP) nanocomposite. The release profiles showed an initially fast release, which became slower as time progressed. The percentage of drug released after 350 minutes was around 100%, and the best fit mathematical model for drug release was the pseudo-second order model. The Strep-CS-MNP nanocomposite showed enhanced antibacterial activity against methicillin-resistant Staphylococcus aureus. This study forms a significant basis for further investigation of the Strep-CS-MNP nanocomposite in the treatment of various bacterial infections.

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