# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
### Assumptions of Targeted Drug Delivery Systems  
Drug delivery systems (DDSs) refer to technological platforms that prepare and retain drug molecules in appropriate formats for administration [19; 20]. Regardless of the route of administration of the active substance (oral, parenteral, ocular, nasal, or rectal/vaginal), it is successively absorbed, distributed, metabolized, and finally excreted. The absorption to the bloodstream occurs by active or passive transport. The desired course of drug release over time should guarantee a constant drug dose over time (zero-order kinetics model), an initially high dose to reach a constant level (first-order kinetics), or a slow drug release over a long period (sustained release). First-generation DDSs are traditional forms of drug administration (capsules, tablets, creams, syrups, etc.) with several limitations, including poor absorption and bioavailability, high metabolism, and repeated dosing. Therefore, research has been conducted on controlled DDSs, which allow for the released drug to be maintained at a constant level and, consequently, obtain a therapeutic effect over a long time [21]. Another generation of drug delivery systems is more sophisticated as it is responsible for drug delivery to specific tissues/organs. Thus, targeted DDSs reduce the active substance's dose and reduce side effects on nearby tissues/organs. Targeted drug delivery is accomplished through passive and active targeting. In passive targeting, the transmission into the targeted receptor occurs due to a change in a specific property of the system (pH, temperature, size). On the other hand, active targeting involves modifying the drug carrier with a unit (e.g., antibody, aptamer, peptide) with affinity only for targeted cells. Finally, the most sophisticated DDSs include nanorobots, gene delivery systems, or long-term systems (delivery up to 1 year) [22]. Different mechanisms can be used to control the drug release process. Traditional DDSs are mostly dissolution- or diffusion-controlled systems. Controlled DDSs can be categorized as diffusion, osmosis, and swelling control. Additionally, DDSs constructed of biodegradable polymers demonstrate chemically controlled release due to their degradation in biological processes. However, a crucial element of developing controlled and targeted DDSs was the use of systems sensitive to a specific stimulus--stimuli-responsive DDSs. Such DDSs can be categorized into two primary groups, depending on the type of stimuli--physical or chemical. More advanced DDSs have units sensitive to several stimuli, allowing for better control of a single active agent's (or several active agents') release at the desired target locations. Physical stimuli-responsive DDSs include systems sensitive to temperature, light, magnetic field, or ultrasound wave. Temperature is the most often applied physical stimulus. Thermo-responsive DDSs contain polymers that behave differently depending on the lower critical solution temperature. The drug loading process occurs below this temperature for soluble and hydrated polymers, while drug release occurs above this temperature due to the polymers' dehydration. On the other hand, stimulation by light requires incorporation into DDSs' photosensitive unit, while magnetic-responsive DDSs contain magnetic nanoparticles (including magnetite NPs) sensitive to an external magnetic field. In turn, ultrasound waves penetrate the tissues deep, and the release process from such DDSs occurs through mechanical effects (via acoustic cavitation) and thermal effects (via acoustic radiation). The most common chemical stimuli are pH-responsive DDSs. Depending on the desired area of drug release, the carriers contain units (polymers) sensitive to acidic (poly-bases) or basic (polyacids) pH. In turn, redox-responsive DDSs are decomposed in the desired environment due to the redox reaction.