Nanoscience and nanotechnology are the most important research areas in modern science and allow researchers to produce important advances in healthcare science. Nanoscale drug delivery platforms have gained importance over the past few decades, which have shown promising clinical results in treating varieties of cancer and inflammatory disorders. This selective administration enhances therapeutic drug efficacy at targeted sites while minimizing the adverse side effects. The use of nanomaterials as carriers for drugs or other bioactive therapeutic agents has been widely investigated, with the focus to improve therapeutic effect, on-site release, and lowering of side effects of the administered drugs. Among magnetic materials, Fe3O4 nanoparticles (NPs) are extensively studied and are considered as promising drug carriers in nanomedicine, owing to their various advantages such as their unique size, excellent biocompatibility, strong affinity, extremely low toxicity, biodegradability, surface reactivity, superparamagnetic nature and other properties making them preferable from traditionally used materials [1,2,3,4,5]. Many regular treatment therapies have limitations in efficacy, which has led to the necessity of nanomedical innovations. A balanced perception of the relationship between inorganic nanomaterials and the biological system has led to the emergence of better solutions for individualized therapy regimes. The composite inorganic–organic NPs have significantly enhanced the identification, quantification of specific disease biomarkers, improving the clinical translation and utility of nanomaterials in the field of medicine [6, 7]. Several metals and metal oxide NPs have been investigated for biomedical use. ZnO NPs synthesized through eco-friendly and natural sources has shown promising results as antibacterial, antibiofilm and other biomedical applications [8].
Antimicrobial approach based on magnetic nanoparticles (MNPs)
Microbial infections are listed among the major health concerns, occurring globally, where in the recent past a variety of fungi, yeasts, and several other pathogenic microorganisms, are responsible for developing a drug resistance thereby enhancing frequency and occurrence of infections. Antimicrobial resistance (AMR) has led to high rates of mortality, economic losses, worsening of health care, increased diagnosis and treatment losses, thus giving rise to a need to develop new antibacterial agents and strategies against drug-resistant super-bugs [9]. One of the most enticing antimicrobial strategies is based on the use of MNPs to transport and control the release of active drugs at the diseased site. Due to the development of AMR to synthetic drugs, a strategy to use plant compounds having antimicrobial properties is being harnessed. MNPs being permeable to tissues and cells can be magnetically targeted to reach specific sites inside the body. This way the bioactive drugs can be delivered at the diseased site which conventional drugs may not reach by themselves. Additionally, this could also minimize undesirable side effects [10]. Due to targeted action, the toxic effects of drugs on healthy tissues can be avoided.
Fe3O4 conjugates as promising nanosystems
MNPs are attractive materials to develop novel routes for Targeted Drug Delivery (TDD) because of their well-developed surface chemistry, significant surface/area ratio, and superparamagnetism. Moreover, applications in biosystems require MNPs to be stable in water at pH 7 and in the physiological environment [10]. Fe3O4 NPs are preferred as it contains Fe+2 ions that have the potential to act as an electron donor. Though, they are magnetic materials, their residual magnetization is zero, a property observed to be beneficial to avoid coagulation which further lowers the in vivo agglomeration. Additionally, their high surface activity is vulnerable to oxidation in the air, affecting their magnetic and dispersibility property. Therefore, the functionalization of Fe3O4 NPs with hydrophilic and biocompatible polymers coating, prevents oxidation and provides colloidal stability, enhanced dispersibility, and ensures chemical binding/conjugation sites for drug molecules and other therapeutic agents to the superparamagnetic Fe3O4, thereby optimizing the biomedical utility for TDD [11,12,13,14].
The drug can be thus targeted to the desired site using an external magnetic field, avoiding delivery to healthy tissues. Fe3O4 NPs have been used with various synthetic and natural drugs to inhibit microbes that could cause serious infectious diseases. As they occur naturally in the human heart, spleen, and liver; they have been approved for clinical use by Food and Drug Administration (FDA) [3, 10]. Being nanosized, smaller concentrations of drug can be adsorbed on the particles and thus reducing the side effects and the exposure of the drug concentration at the infection site. The release of the drug can be controlled with respect to time of release and dosage [10, 15]. Bifunctional Fe3O4@Ag NPs prepared by reducing Ag ions on the surface of Fe3O4 NPs show both superparamagnetic and antibacterial properties [16]. Fatty acids assisted biologically synthesized superparamagnetic γ- Fe2O3 NPs ensure the stability to the NPs. They were investigated for antimicrobial, antibiofilm, and anti-cancer biomedical applications. Magnetic property was an advantage to boost the biological activity of γ- Fe2O3 NPs by the application of external magnetic field or in blend with other therapeutic drugs [17].
Simarouba glauca commonly known as Laxmitaru (Lax) plant was used as herbal medicine against dysentery. The crude bark and leaf water extracts contains active phytochemicals having several pharmacological properties such as antipyretic, hemostatic, anticancerous, antiparasitic, and anthelmintic besides antidysenteric properties [18]. Quassinoids are the major group of phytochemicals present and to date approximately 200 of them are isolated and structures elucidated [19]. In the present study, the concentrated water extract of Lax was explored as the natural biocompatible organic coating on Fe3O4 NPs to stabilize the molecule. Thus making it immune friendly, being non-toxic with known medicinal benefits. Quassinoids present in the plant extract have antimalarial and cytotoxicity effects against several human cancer cell lines [18].
Eugenol (Eug) is an allyl chain-substituted guaiacol, i.e., 2-methoxy-4-(2-propenyl) phenol. It is a member of the allylbenzene class, colorless to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, and bay leaf. It is slightly soluble in water and soluble in organic solvents. Eug is used in perfumeries, flavorings, and in medicine as a local analgesic (topical), antiseptic, antifungal, and an anesthetic. Eug possesses significant antioxidant, anti-inflammatory, and cardiovascular properties [20].
Ylang-Ylang (Yla) is an essential oil from Cananga Odorata, a perfumed tree (medicinal) bearing yellow flowers. Extensively used by perfume, food industry, and aromatherapy for its powerful floral fragrance and flavor. It is water-insoluble and contains sesquiterpenes, monoterpenes, phenols, methyl benzoate, benzyl acetate, geranyl acetate, linalool, geraniol which contribute to its medicinal property. It has a vast spectrum of pharmacological activities such as antioxidant, antibiofilm, antimicrobial, antifungal, antiinflammatory, insect repellent, antidiabetic, antimalarial, antiseptic, additionally it has curative properties for internal infections of the colon, etc.[21].
The objectives of this investigation were to synthesize Lax-coated Fe3O4 phytochemical nanoparticles, load them with plant-derived bioactive drugs Eug and Yla, to characterize and confirm their structural morphology, the percentage of drug loading, evaluate antimicrobial and antioxidant activity. These characteristics contribute to the description as promising molecules in the development of a new strategy of drug delivery.