Magnetic properties of polyvinyl alcohol and doxorubicine loaded iron oxide nanoparticles for anticancer drug delivery applications

The current study emphasizes the synthesis of iron oxide nanoparticles (IONPs) and impact of hydrophilic polymer polyvinyl alcohol (PVA) coating concentration as well as anticancer drug doxorubicin (DOX) loading on saturation magnetization for target drug delivery applications. Iron oxide nanoparticles particles were synthesized by a reformed version of the co-precipitation method. The coating of polyvinyl alcohol along with doxorubicin loading was carried out by the physical immobilization method. X-ray diffraction confirmed the magnetite (Fe3O4) structure of particles that remained unchanged before and after polyvinyl alcohol coating and drug loading. Microstructure and morphological analysis was carried out by transmission electron microscopy revealing the formation of nanoparticles with an average size of 10 nm with slight variation after coating and drug loading. Transmission electron microscopy, energy dispersive, and Fourier transform infrared spectra further confirmed the conjugation of polymer and doxorubicin with iron oxide nanoparticles. The room temperature superparamagnetic behavior of polymer-coated and drug-loaded magnetite nanoparticles were studied by vibrating sample magnetometer. The variation in saturation magnetization after coating evaluated that a sufficient amount of polyvinyl alcohol would be 3 wt. % regarding the externally controlled movement of IONPs in blood under the influence of applied magnetic field for in-vivo target drug delivery

Discovery of novel isonipecotic acid-based heteroaryl amino acid derivatives as potential anticonvulsant agents: Design, synthesis, in-silico ADME study, and molecular docking studies

Background: Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsions, and odd behavior. Several substituted-(naphthalen-2-yl)-3-(1H-indol-3-yl) allyl)-1,4-dihydropyridine-4-carboxylic acid derivatives (5a-j) were intended to be produced in the current research effort to reduce convulsions and seizures. Materials and Methods: The newly developed compounds were produced by the prescribed process. Numerous methods (infrared spectroscopy (IR), nuclear magnetic resonance (NMR), mass, elemental analysis, etc.) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed absorption, distribution, metabolism, and excretion (ADME) predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the gamma amino butyric acid (GABA)-A target protein. Results: Anticonvulsant screening results identified compounds 5f, 5h, 5d, and 5b as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with LEU B: 99, TYR A: 62, Ala A: 174, and THR B: 202, and the outcomes were good and in agreement with in vivo findings. Conclusions: The study's findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogs may therefore represent a possible lead, and additional studies may result in a potential new drug candidate

SPIONs Conjugate Supported Anticancer Drug Doxorubicin’s Delivery: Current Status, Challenges, and Prospects

Considerable efforts have been directed towards development of nano-structured carriers to overcome the limitations of anticancer drug, doxorubicin’s, delivery to various cancer sites. The drug’s severe toxicity to cardio and hepatic systems, low therapeutic outcomes, inappropriate dose–demands, metastatic and general resistance, together with non-selectivity of the drug have led to the development of superparamagnetic iron oxide nanoparticles (SPIONs)-based drug delivery modules. Nano-scale polymeric co-encapsulation of the drug, doxorubicin, with SPIONs, the SPIONs surface end-groups’ cappings with small molecular entities, as well as structural modifications of the SPIONs’ surface-located functional end-groups, to attach the doxorubicin, have been achieved through chemical bonding by conjugation and cross-linking of natural and synthetic polymers, attachments of SPIONs made directly to the non-polymeric entities, and attachments made through mediation of molecular-spacer as well as non-spacer mediated attachments of several types of chemical entities, together with the physico-chemical bondings of the moieties, e.g., peptides, proteins, antibodies, antigens, aptamers, glycoproteins, and enzymes, etc. to the SPIONs which are capable of targeting multiple kinds of cancerous sites, have provided stable and functional SPIONs–based nano-carriers suitable for the systemic, and in vitro deliveries, together with being suitable for other biomedical/biotechnical applications. Together with the SPIONs inherent properties, and ability to respond to magnetic resonance, fluorescence-directed, dual-module, and molecular-level tumor imaging; as well as multi-modular cancer cell targeting; magnetic-field-inducible drug-elution capacity, and the SPIONs’ magnetometry-led feasibility to reach cancer action sites have made sensing, imaging, and drug and other payloads deliveries to cancerous sites for cancer treatment a viable option. Innovations in the preparation of SPIONs-based delivery modules, as biocompatible carriers; development of delivery route modalities; approaches to enhancing their drug delivery-cum-bioavailability have explicitly established the SPIONs’ versatility for oncological theranostics and imaging. The current review outlines the development of various SPIONs-based nano-carriers for targeted doxorubicin delivery to different cancer sites through multiple methods, modalities, and materials, wherein high-potential nano-structured platforms have been conceptualized, developed, and tested for, both, in vivo and in vitro conditions. The current state of the knowledge in this arena have provided definite dose-control, site-specificity, stability, transport feasibility, and effective onsite drug de-loading, however, with certain limitations, and these shortcomings have opened the field for further advancements by identifying the bottlenecks, suggestive and plausible remediation, as well as more clear directions for future development

Combined Anti-Bacterial Actions of Lincomycin and Freshly Prepared Silver Nanoparticles: Overcoming the Resistance to Antibiotics and Enhancement of the Bioactivity

Bacterial drug resistance to antibiotics is growing globally at unprecedented levels, and strategies to overcome treatment deficiencies are continuously developing. In our approach, we utilized metal nanoparticles, silver nanoparticles (AgNPs), known for their wide spread and significant anti-bacterial actions, and the high-dose regimen of lincosamide antibiotic, lincomycin, to demonstrate the efficacy of the combined delivery concept in combating the bacterial resistance. The anti-bacterial actions of the AgNPs and the lincomycin as single entities and as part of the combined mixture of the AgNPs–lincomycin showed improved anti-bacterial biological activity in the Bacillus cereus and Proteus mirabilis microorganisms in comparison to the AgNPs and lincomycin alone. The comparison of the anti-biofilm formation tendency, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) suggested additive effects of the AgNPs and lincomycin combination co-delivery. The AgNPs’ MIC at 100 μg/mL and MBC at 100 μg/mL for both Bacillus cereus and Proteus mirabilis, respectively, together with the AgNPs–lincomycin mixture MIC at 100 + 12.5 μg/mL for Bacillus cereus and 50 + 12.5 μg/mL for Proteus mirabilis, confirmed the efficacy of the mixture. The growth curve test showed that the AgNPs required 90 min to kill both bacterial isolates. The freshly prepared and well-characterized AgNPs, important for the antioxidant activity levels of the AgNPs material, showed radical scavenging potential that increased with the increasing concentrations. The DPPH’s best activity concentration, 100 μg/mL, which is also the best concentration exhibiting the highest anti-bacterial zone inhibition, was chosen for evaluating the combined effects of the antibiotic, lincomycin, and the AgNPs. Plausible genotoxic effects and the roles of AgNPs were observed through decreased Bla gene expressions in the Bacillus cereus and BlaCTX-M-15 gene expressions in the Proteus mirabilis

Optimal system, invariant solutions and dynamics of the solitons for the Wazwaz Benjamin Bona Mahony equation

In this article, the nonlinear (3+1) dimensional Wazwaz Benjamin Bona Mahony (WBBM) equation is considered for analysis which is related to some specific undular bore evolution through a long wave in shallow water. One-dimensional optimal system of Lie infinitesimal generators, associated vector field, commutation relations, and adjoint representation for the WBBM equation are illustrated. Moreover, the symmetry reductions are made, and closed-form solutions of the WBBM equation are obtained based on the optimal system. In addition, we make use of the transnational symmetries to reduce the governing equation to a nonlinear ordinary differential equation which is solved using the new extended direct algebraic method (NEDAM) to obtain the traveling wave profile of the WBBM equation

Functional Analysis of CaIPT1, a Sphingolipid Biosynthetic Gene Involved in Multidrug Resistance and Morphogenesis of Candida albicans

In the present study we describe the isolation and functional analysis of a sphingolipid biosynthetic gene, IPT1, of Candida albicans. The functional consequence of the disruption of both alleles of IPT1 was confirmed by mass analysis of its sphingolipid composition. The disruption of both alleles or a single allele of IPT1 did not lead to any change in growth phenotype or total sphingolipid, ergosterol, or phospholipid content of the mutant cells. The loss of mannosyl diinositol diphosphoceramide [M(IP)(2)C] in the ipt1 disruptant, however, resulted in increased sensitivity to drugs like 4-nitroquinoline oxide, terbinafine, o-phenanthroline, fluconazole, itraconazole, and ketoconazole. The increase in drug susceptibilities of ipt1 cells was linked to an altered sphingolipid composition, which appeared to be due to the impaired functionality of Cdr1p, a major drug efflux pump of C. albicans that belongs to the ATP binding cassette superfamily. Our confocal and Western blotting results demonstrated that surface localization of green fluorescent protein-tagged Cdr1p was affected in ipt1 disruptant cells. Poor surface localization of Cdr1p resulted in an impaired ability to efflux fluconazole and rhodamine 6G. The effect of mannosyl inositol phosphoceramide accumulation in the ipt1 mutant and the absence of M(IP)(2)C from the ipt1 mutant on the efflux of drug substrates was very selective. The efflux of methotrexate, a specific substrate of CaMdr1p, another major efflux pump of major facilitator superfamily, remained unaffected in ipt1 mutant cells. Interestingly, changes in sphingolipid composition affected the ability of mutant cells to form proper hyphae in various media. Taken together, our results demonstrate that an altered composition of sphingolipid, which is among the major constituents of membrane rafts, affects the drug susceptibilities and morphogenesis of C. albicans

Silicalite‑1 As Efficient Catalyst for Production of Propene from 1‑Butene

Reaction of 1-butene was studied over silicalite-1 and H-ZSM-5 zeolites with different Al contents (SiO₂/Al₂O₃ molar ratio (Si/Al₂) = 23, 80, and 280) to explore an efficient catalyst for the formation of propene as well as to elucidate the reaction scheme and the relevant acid sites involved in the reaction. The formation of alkenes, including propene, increased and those of alkanes and aromatics decreased with decreasing Al content. The percentage of alkenes other than <i>n</i>-butene isomers was 60 C-wt % over silicalite-1 at 550 °C with 34.1 C-wt % propene. Over H-ZSM-5 with Si/Al₂ = 23, the formation of alkenes was negligible, and the main products were alkanes and aromatics, the sum of alkanes and aromatics being 65.4 C-wt % at 550 °C. These product distributions are consistently interpreted by the successive reactions of oligomerization, cracking, and hydrogen transfer. For oligomerization and cracking, in addition to strong acid sites on H-ZSM-5 zeolites, weak acid sites present on silicalite-1 act as active sites. For the hydrogen transfer reaction of alkenes to form alkanes and aromatics, strong acid sites are required. The scheme can also be applicable to the reactions of 1-pentene and 1-hexene. The weak acid sites on silicalite-1 are assumed to be the silanol groups that act as Brønsted acid above 300 °C. The presence of strong acid sites on H-ZSM-5 catalysts, which are the OH groups bridging to Si and Al, results in the consumption of alkenes by hydrogen transfer. Removal of a part of Al contained in silicalite-1 as an impurity and enrichment of surface silanol groups on silicalite-1 resulted in the improvement of the propene yield. It is concluded that silicalite-1 is an efficient catalyst for the formation of propene by the reactions of light alkenes because of the absence of strong acid sites and the presence of weak acid sites