The State of the Art of Natural Polymer Functionalized Fe3O4 Magnetic Nanoparticle Composites for Drug Delivery Applications: A Review

Abstract

Natural polymers have received a great deal of interest for their potential use in the encapsulation and transportation of pharmaceuticals and other bioactive compounds for disease treatment. In this perspective, the drug delivery systems (DDS) constructed by representative natural polymers from animals (gelatin and hyaluronic acid), plants (pectin and starch), and microbes (Xanthan gum and Dextran) are provided. In order to enhance the efficiency of polymers in DDS by delivering the medicine to the right location, reducing the medication's adverse effects on neighboring organs or tissues, and controlling the medication's release to stop the cycle of over- and under-dosing, the incorporation of Fe₃O₄ magnetic nanoparticles with the polymers has engaged the most consideration due to their rare characteristics, such as easy separation, superparamagnetism, and high surface area. This review is designed to report the recent progress of natural polymeric Fe₃O₄ magnetic nanoparticles in drug delivery applications, based on different polymers' origins.

Keywords: animal; composites; drug delivery; magnetic nanoparticles; microbe; natural polymer; plant.

Figure 1

A brief history of the development of natural polymer applications in drug delivery systems. 5-FU: 5-fluorouracil; DTT: dithiothreitol; FDA: food drug administration; NIR: near infrared radiation; NPs: nanoparticles.

Figure 2

General mechanism of delivering drugs to the targeted cell by natural polymer.

Figure 3

Schematic representation of the amphiphilic gelatin nanocarrier loaded with quercetin preparation and the mechanism of drug release. Keloid scarring can be treated by the transdermal delivery of drug combinations (Qu and gallic acids) via actions of gelatin-based MN composite heterogeneously. Adapted from Chen et al. [22].

Figure 4

Illustrative synthesis of multi-responsive HA-derived hydrogel diselenide bonds cleavage mechanism under different triggers and the actions of drug release. Adapted from Jo et al. [38]. DTT: 1,4-dithiothreitol; NIR: Near-infrared.

Figure 5

Synthesis structure of INS/DFAN dual-crosslinked. Adapted from Zhang et al. [39].

Figure 6

Graphic representation of the LDH(Mg–Al) production, co-drug payload, LDH(Mg-Al)@DOX,5-Fu coating with CMS, and the suggested method for the drug molecule releases from CMS@LDH(Mg–Al)@DOX,5-Fu microspheres. Adapted from Ranjbar et al. [44].

Figure 7

Summary of applications of xanthan gum (XG) in oral and transdermal drug delivery systems (DDS). Oral DDSs can be achieved by incorporating XG-based hydrogel particles loaded with repaglinide to treat type 2 diabetes and XG-based mouth-dissolving films (MDFs) loaded with glibenclamide to treat type 2 diabetes or amlodipine to treat hypertension. Transdermal DDSs can be achieved by incorporating XG-based gel with hesperidin-loaded gold nanoparticles to treat P. vulgaris infection.

Figure 8

Multi-responsive dextran-based drug delivery vehicle to deliver doxorubicin (DOX) drug for cancer treatments. DOX is loaded into dextran-based micelles that are responsive to internal stimuli (i.e., changes in the pH tumor environment). DOX also can be loaded into a dextran-based nanodroplet that is responsive to external stimuli such as ultrasound. This multi-responsive DDS allows drugs to be delivered in a more targeted manner such as in tumor cells. The micelles and nanodroplets enter the tumor environment through leaky vasculature. DOX will only be released into the tumor cells upon response to pH changes or ultrasound stimuli.

Figure 9

Schematic of an EMF-influenced magnetic drug delivery system. Adapted from Park et al. [71].

Figure 10

Proposed mechanism interaction between Fe₃O₄, gelatin, and loaded drug. Adapted from Sirivat et al. [91].

Figure 11

A proposed creation of HA-MSNs for targeted cancer treatment in vivo and pH-responsive drug release following specific binding with cancer cells. Adapted from Fang et al. [95].

Figure 12

Illustration of (A) 5-fluorouracil-loaded pectin-coated Fe₃O₄ MNPs; (B) porous poly(butylene succinate co adipate). Adapted from Viratchaiboott et al. [96].

Figure 13

Albumin release from a hydrogel without and with an applied magnetic field: a proposed mechanism. Adapted from Guilherme et al. [97].

Figure 14

Mechanism of actions of oral drug and transdermal drug delivery by Fe₃O₄ MNPs. Oral drug delivery: Oral route administration is achieved by ingesting an oral tablet containing a drug loaded in the natural polymer coated with Fe₃O₄ MNPs. Stable Fe₃O₄ MNPs only produce a slow drug release in the stomach but high drug release in the targeted site such as in the colorectal region upon exposure to an external magnetic field (EMF). Transdermal drug delivery: a transdermal patch with the drug loaded in natural polymers coated with Fe₃O₄ MNPs is placed on the skin, and an EMF is applied to trigger drug release from the Fe₃O₄ MNPs directly into the bloodstream.