**1. Introduction**

Nanoparticles have gained considerable attention among researchers as a potential drug delivery system due to their unique properties, such as their high surface-to-volume ratio and surface charge-dependent behavior, compared to their bulk counterparts [1–3]. The properties of nanoparticles depend on their size and shape, which can be tailored by selecting an appropriate synthesis approach [4]. Dendrimers, micelles, liposomes, and biopolymers are the most commonly used drug-delivery nanoparticles [5]. Micelles are colloidal suspensions formed by the dispersion of amphiphilic lipid molecules in a liquid and have a hydrophilic head and a hydrophobic tail [6]. Micelles as a drug delivery system have advantages such as improved solubility of highly lipophilic drugs, controlled drug release, the ability to adjust their physiochemical properties, and protection of the drug from environmental factors. However, they have limitations such as low drug-loading capacity, high dependence on critical micelle concentration, and limited applicability to only

**Citation:** Jeevanandam, J.; Tan, K.X.; Rodrigues, J.; Danquah, M.K. Target-Specific Delivery and Bioavailability of Pharmaceuticals via Janus and Dendrimer Particles. *Pharmaceutics* **2023**, *15*, 1614. https://doi.org/10.3390/ pharmaceutics15061614

Academic Editor: Barbara Stella

Received: 9 May 2023 Revised: 25 May 2023 Accepted: 26 May 2023 Published: 29 May 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

lipophilic drugs [7]. Liposomes are small artificial spherical vesicles formed using natural, nontoxic phospholipids and cholesterol and have benefits such as biocompatibility and hydrophilic/hydrophobic characteristics [8]. However, liposomes as a drug delivery system face limitations such as high production cost, limited shelf life, vulnerability to oxidation and hydrolysis of phospholipids in certain conditions, instability, fusion, and potential release of encapsulated drugs [9]. Biopolymers (polymers synthesized or extracted from biological source) have also been used for drug formulation, but they often lack solubility or have pH-dependent solubility, which limits their use [10,11].

Dendrimers are synthetic, tree-like hyperbranched polymers with a high number of functional groups and an open molecular structure. They are designed as artificial macromolecules with void spaces for drug storage and targeted release [12–14]. However, dendrimers have limitations such as high non-specific toxicity, drawbacks during scale-up experiments, and low hydro-solubility [15]. Despite these limitations, they have potential as nanoparticles for drug delivery. Janus nanoparticles are a recent addition to the range of nanoparticles, featuring the integration of two or more chemically distinct components into a single structure. They possess unique properties based on their synthesis approaches and the materials infused into the Janus structure [16–19]. However, the complex synthesis process and toxicity due to chemicals involved in the synthesis approach are limitations of Janus nanoparticles [17,20]. The incorporation of Janus and dendrimer into a composite material has been proposed to enhance drug delivery ability and reduce limitations [21,22]. This article discusses various nanosized Janus and dendrimer particles for target-specific delivery and bioavailability of pharmaceuticals. Additionally, the emergence of Janusdendrimer nanoparticles to overcome the limitations of standalone nanosized Janus and dendrimer particles is discussed.

### **2. Overview of Nanosized Janus and Dendrimer Particles**

### *2.1. Janus Nanoparticles*

Janus nanoparticles were first discovered by Pierre-Gilles de Gennes, the Nobel Laureate who pioneered fabricating microparticles 'Janus grains' with an apolar and polar side [23]. The word 'Janus' comes from the two-faced Roman God of gates, which defines Janus nanoparticles as anisotropic particles that possess two different compartments with varying functionalities, material compositions, morphology, size, shape, and biochemical properties. Janus nanoparticles are originally from polymeride but can be subcategorized as organic/polymeric, inorganic, or hybrid of organic and inorganic Janus particles [24–27]. In addition to the typical spherical shape, Janus nanoparticles can be fabricated into different conformations, which include rod [28], dumbbell [29], platelet [30], and snowman [31,32].

Due to their asymmetric faces, Janus nanoparticles can improve the stability of different phases [33]. This has then broadened their biomedical and clinical applications from emulsion stabilizer, bio-sensing, bio-catalysis, molecular imaging, and diagnostic tools to pharmaceutical targeted drug delivery systems [34], offering significant benefits over the conventional mono-functional particles. This is highly ascribed to the tunable properties of Janus nanoparticles whereby their different surfaces or compartments can be modified with individual functionality. This includes hybrid particles with one amphiphilic surface and another stimuli-responsive surface [19]; Janus nanoparticles made of organic and inorganic compartments [35]; or biocompatible particles [36] for targeted medical treatments.

This enables Janus nanoparticles to be utilized as delivery carriers to carry different drug molecules with the combination of various functionalities. Otherwise, as a delivery system, one hemisphere can load medical drug molecules while another side acts as a targeting element with high specificity toward targeted cells. Janus nanoparticles have practical medical and environmental applications, such as detecting water contaminants and environmental pollutants and serving as superior candidates for cancer theranostics due to their high loading capacity and tunable properties. Janus nanoparticles made of silver/chitosan have also been reported to exhibit high antimicrobial effects against bacteria such as *Escherichia coli*, *Salmonella choleraesuis*, *Bacillus subtilis*, *Staphylococcus aureus*, indicating their

potential applications in food sector [37]. Interestingly, there are Janus nanoparticles used to detect DNA and metals for monitoring applications. A streptavidin-modified retroreflective Janus particle can selectively sense the presence of mercury ions with up to 0.027 nM detection limit [38] whilst a hybrid of gold-silver nanorod and polyaniline has also been developed as a Janus nanoparticle, serving as a surface-enhanced Raman scattering sensor for the detection of mercury [39]. In addition, gold-silver Janus nanoparticles have been exploited as aptasensor to detect toxins such as Ochratoxin A quantitatively, which can be widely used in real systems, including red wine monitoring [40]. The above examples highlight the vast potential of Janus nanoparticles for a broad range of applications, offering numerous benefits to various industries.
