Potential of Exosomes as Multifunctional Nanocarriers for Targeted Drug Delivery.

Exosomes are small vesicles that form when multivesicular bodies fuse with the plasma membrane and are released into body fluids. They play a vital role in facilitating communication between cells by transferring different biomolecules, including DNA, RNA, proteins, and lipids, over both short and long distances. They also function as vital mediators in both states of health and disease, exerting an impact on several physiological processes. Exosomes have been modified to overcome the limitations of natural exosomes to enhance their potential as carriers for drug delivery systems, and these modifications aim to improve the drug delivery efficiency, enhance tissue and organ targeting, and prolong the circulating half-life of exosomes. This review discussed recent advancements in exosome nanotechnology, as well as the progression and use of exosomes for drug delivery. The potential commercialisation and challenges associated with the use of exosome-based drug delivery systems were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.

Ultrasound-Assisted Preparation of Hyaluronic Acid-Based Nanocapsules with an Oil Core.

Liquid-core nanocapsules (NCs) coated with amphiphilic hyaluronic acid (AmHA) have been proposed for the preparation of drug and food formulations. Herein, we focused on the use of ultrasound techniques to (i) optimize the polysaccharide chain length with respect to the properties of NCs stabilized with AmHAs and (ii) form oil-core nanocapsules with a coating composed of AmHAs. The results indicate that sonication is a convenient and effective method that allows for a controlled reduction in HA molecular weight. The initial (H-HA) and degraded (L-HA) polysaccharides were then reacted with dodecylamine to obtain hydrophobic HA derivatives (HA-C12s). Then, NCs were prepared based on HA-C12s using ultrasound-assisted emulsification of glyceryl triacetate oil. The nanocapsules coated with L-HA-C12 showed greater stability compared to the longer-chain polysaccharide. Molecular dynamics (MD) simulations revealed that HA-C12 readily adsorbs at the water-oil interphase, adopting a more compact conformation compared to that in the aqueous phase. The dodecyl groups are immersed in the oil droplet, while the main polysaccharide chain remaining in the aqueous phase forms hydrogen bonds or water bridges with the polar part of the triglycerides, thus increasing the stability of the NC. Our research underscores the usefulness of ultrasound technology in preparing suitable formulations of bioactive substances.

Unleashing the power of silk-based proteins as biomaterials for cutting-edge drug delivery: a comprehensive review.

Silk proteins, viz., sericin, fibroin and their modified forms etc., have been thoroughly researched as natural biopolymers for the development of varied nanomaterials exhibiting diverse biomedical applications. The silk proteins are extracted from the cocoons by degumming and treatment with soaps, followed by dissolution and dialysis against water. These proteins exhibit distinct mechanical and physicochemical characteristics including biocompatibility, controlled biodegradability, self-assembling traits, chemical modifiability, and adaptability, thus making it an ideal drug delivery vehicle. In this regard, silk protein-derived drug delivery systems have been reported as efficient carrier to encapsulate and stabilize the wide variety of pharmacological molecules, enzymes, proteins, vaccines, and even DNA, allowing them to remain active for a longer period of time. Further, different delivery carriers researched employing these proteins for multitude of applications include hydrogels, sponges, fibres, scaffolds and particulate delivery systems. Additionally, the chemical modification of silk proteins has further opened avenues for development of other modified silk proteins with improved physicochemical traits and hence exhibiting enormous potential in development of varied bioenhanced carrier systems. The current article thus provides the holistic information of characteristics, types of silk protein-based delivery carriers, and their fabrication techniques, while emphasizing the applications of different silk proteins in biomedicine and drug delivery.

Overcoming resistance: Chitosan-modified liposomes as targeted drug carriers in the fight against multidrug resistant bacteria-a review.

Antimicrobial resistance (AMR) poses a significant global health threat, rendering standard antibiotics ineffective against multi-drug resistant bacteria. To tackle this urgent issue, innovative approaches are essential. Liposomes, small spherical vesicles made of a phospholipid bilayer, present a promising solution. These vesicles can encapsulate various medicines and are both biocompatible and biodegradable. Their ability to be modified for targeted tissue or cell uptake makes them an ideal drug delivery system. By delivering antibiotics directly to infection sites, liposomes minimize side effects and reduce the development of resistance. However, challenges such as poor stability and rapid drug leakage limit their biological application. Chitosan, a biocompatible polymer, enhances liposome interaction with specific tissues or cells, enabling selective drug release at infection sites. Incorporating chitosan into liposome formulations alters and diversifies their surface characteristics through electrostatic interactions, resulting in improved stability and pH-sensitive drug release. These interactions are crucial for enhancing drug retention and targeted delivery, especially in varying pH environments like tumor sites or infection areas, thereby improving therapeutic outcomes and reducing systemic side effects. This review discusses recent advancements, challenges, and the need for further research to optimize liposome formulations and enhance targeted drug delivery for effective AMR treatment. Chitosan-modified liposomes offer a promising strategy to overcome AMR and improve antimicrobial therapies.

In vivo Fate of Targeted Drug Delivery Carriers.

This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.

Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a "car" or under an "umbrella") plays an essential role in the drug's therapeutic effect. This paper aims to highlight the importance of the carrier's role, which is vital for developing new drugs and advancing basic research.

Residue-Free Orally Administered Drug Carrier Based on a Porous Aromatic Framework for Efficient Multisite Treatment.

Nowadays, oral medications are the primary method of treating disease due to their convenience, low cost, and safety, without the need for complex medical procedures. To maximize treatment effectiveness, almost all oral medications utilize drug carriers, such as capsules, liposomes, and sugar coatings. However, these carriers rely on dissolution or fragmentation to achieve drug release, which leads to drugs and carriers coabsorption in the body, causing unnecessary adverse drug reactions, such as nausea, vomiting, abdominal pain, and even death caused by allergy. Therefore, the ideal oral drug carrier should avoid degradation and absorption and be totally excreted after drug release at the desired location. Herein, a gastrointestinally stable oral drug carrier based on porous aromatic framework-1 (PAF-1) is constructed, and it is modified with famotidine (a well-known gastric drug) and mesalazine (a well-known ulcerative colitis drug) to verify the excellent potential of PAF-1. The results demonstrate that PAF-1 can accurately release famotidine in stomach, mesalazine in the intestine, and finally be completely excreted from the body without any residue after 12 h. The use of PAF materials for the construction of oral drug carriers with no residue in the gastrointestinal tract provides a new approach for efficient disease treatment.

Combined Theoretical and Experimental Investigations: Design, Synthesis, Characterization, and In Vitro Cytotoxic Activity Assessment of a Complex of a Novel Ureacellobiose Drug Carrier with the Anticancer Drug Carmustine.

Drug delivery systems (DDSs) are used to transport drugs which are characterized by some pharmaceutical problems to the specific target site, enhancing therapeutic efficacy and reducing off-target accumulation in the body. In this work, one of the recently synthesized molecules, 1,10-N,N'-bis-(ß-ᴅ-ureidocellobiosyl)-4,7,13,16-tetraoxa-1,10-diazacyclooctadecane (TN), was tested as a potential drug carrier towards the anticancer drug carmustine. For this purpose, different techniques were used, from synthesis and calculations to cytotoxicity assessment. Our results showed that TN is characterized by a very compact geometry, which significantly impacts its complexation properties. Although it forms a very stable complex with carmustine, it adopts a non-inclusion geometry, as verified by both experimental and theoretical NMR analyses. The cytotoxicity study performed for all analyzed molecules (TN; carmustine; TN:carmustine complex) towards normal and cancer (breast and colon) cells revealed that TN is not toxic and that the formation of complexes with carmustine reduces the toxicity of carmustine to normal cells.

Engineering of Erythrocytes as Drug Carriers for Therapeutic Applications.

Erythrocytes, also known as red blood cells (RBCs), have garnered considerable attention as potential carriers for drug delivery, owing to their inherent properties such as biocompatibility, biodegradability, and prolonged circulation half-life. This paper presents a comprehensive overview of the role of erythrocytes in drug delivery, elucidating recent advancements in delivering a diverse array of therapeutic agents, including small molecules, nucleic acids, antibodies, protein enzymes, and nanoparticles. Two primary strategies for encapsulating drugs within erythrocytes are systematically discussed: internal loading and surface loading. Each strategy offers distinct advantages in terms of drug stability and release kinetics. Notably, the utilization of erythrocyte membrane camouflaged nanocarriers holds promise for enhancing the biocompatibility of conventional nanoparticles and facilitating targeted drug delivery. Furthermore, the broad spectrum of biomedical applications of erythrocyte-based drug delivery systems are examined, ranging from cancer treatment to diabetes management, thrombosis prevention, and immunotherapy. This review provides a comprehensive evaluation of current technologies in erythrocyte-loaded drug delivery, highlighting the strengths, weaknesses, and future directions for advancing therapeutic interventions in various disease contexts.

Anodic Production and Characterization of Biomimetic Oxide Layers on Grade 4 Titanium for Medical Applications.

Biomaterials are the basis for the development of medicine because they allow safe contact with a living organism. The aim of this work was to produce innovative oxide layers with a microporous structure on the surface of commercially pure titanium Grade 4 (CpTi G4) and to characterize their properties as drug carriers. The anodization of the CpTi G4 subjected to mechanical grinding and electrochemical polishing was carried out in a solution of 1M ethylene glycol with the addition of 40 g of ammonium fluoride at a voltage of 20 V for 2, 18, 24, and 48 h at room temperature. It was found that the longer the anodization time, the greater the number of pores formed on the CpTi G4 surface as revealed using the FE-SEM method, and the greater the surface roughness determined in profilometric tests. As the anodizing time increases, the amount of the drug in the form of gentamicin sulfate incorporated into the resulting pores decreases. The most favorable drug release kinetics profile determined via UV-VIS absorption spectroscopy was found for the CpTi G4 anodized for 2 h.

Recent Progress in Polyion Complex Nanoparticles with Enhanced Stability for Drug Delivery.

Polyion complex (PIC) nanoparticles, including PIC micelles and PICsomes, are typically composed of poly(ethylene glycol) block copolymers coupled with oppositely charged polyelectrolytes or therapeutic agents via electrostatic interaction. Due to a simple and rapid preparation process with high drug-loading efficiency, PIC nanoparticles are beneficial to maintaining the chemical integrity and high biological activity of the loaded drugs. However, the stability of PIC nanoparticles can be disrupted in high-ionic-strength solutions because electrostatic interaction is the DRIVING force; these disruptions can thus impair drug delivery. Herein, we summarize the advances in the use of PIC nanoparticles for delivery of charged drugs, focusing on the different chemical and physical strategies employed to enhance their stability, including enhancing the charge density, crosslinking, increasing hydrophobic interactions, forming hydrogen bonds, and the development of PIC-based gels. In particular, we describe the use of PIC nanoparticles to load peptide antibiotics targeting antibiotic-resistant and biofilm-related diseases and the use of nanoparticles that load chemotherapeutics and gaseous donors for cancer treatment. Furthermore, the application of PIC nanoparticles as magnetic resonance imaging contrast agents is summarized for the first time. Therefore, this review is of great significance for advances in the use of polymeric nanoparticles for functional drug delivery.

A double-edged sword: The complex interplay between engineered nanoparticles and platelets.

Nanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes. In recent years, various studies have helped resolve the physicochemical parameters that influence platelet-NP interactions, and either emphasize nanoparticles' therapeutic role such as to augment hemostasis or to inhibit thrombus formation, or conversely map their potential undesired side effects upon injection. In the present review, we discuss some of the main effects of several key NP types including polymeric, ceramic, silica, dendrimers and metallic NPs on platelets, with a focus on the physicochemical parameters that can dictate these effects and modulate the therapeutic potential of the NP. Despite the scientific and clinical significance of understanding Platelet-NP interactions, there is a significant knowledge gap in the field and a critical need for further investigation. Moreover, improved guidelines and research methodologies need to be developed and implemented. Our outlook includes the use of biomimetic in vitro models to investigate these complex interactions under both healthy physiological and disease conditions.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

Efficacy of hydroxyapatite and fibrin sealant as carriers for bone morphogenetic protein-2 in maxillary sinus floor augmentation: a retrospective study.

The aim of this retrospective study was to assess the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapatite (HA) granules and fibrin sealant (FS) in maxillary sinus floor augmentation (MSFA), with a focus on the volume change. Fifty-two of 137 patients who underwent MSFA with rhBMP-2/HA grafting between June 2016 and December 2022 met the study inclusion criteria; 25 had received rhBMP-2/HA without FS and 27 had received rhBMP-2/HA with FS. Computed tomography (CT) images were obtained preoperatively, immediately following the operation, and at 6 months postoperative. These images were three-dimensionally reconstructed to measure the volumetric and height changes following MSFA. The mean ± standard deviation percentage of volumetric change at 6 months was 48.75 ± 37.44% in the group with FS and 29.77 ± 13.42% in the group without FS (P = 0.019). The vertical height measured at a specific site of the grafted area showed a mean percentage change at 6 months of 4.05 ± 12.08% in the group with FS and 6.07 ± 10.15% in the group without FS (P = 0.518). The additional use of FS as a carrier for rhBMP-2/HA in MSFA was found to improve surgical convenience and bone regeneration ability.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy.

High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.

Multifactorial drug carrier system bringing both chemical and physical therapeutics to the treatment of tumor heterogeneity.

Tumor heterogeneity and drug resistance have been invincible features of cancer for its complete cure. Despite the advent of immunotherapy, the expansion and diversification of cancer cells evolved even in the absence or presence of drug treatment discourage additional therapeutic interventions. For the eradication of cancer cells, therefore, an 'all-at-once' strategy is required, which exploits both target-selective chemotherapy and non-selective physicotherapy. Multifactorial microcapsules comprising gold nanoparticles (AuNPs) and a self-assembly protein of α-synuclein (αS) were fabricated, in which hydrophobic and hydrophilic drugs could be separately encapsulated by employing lipid-based inverted micelles (IMs). Their combined physico-chemical therapeutic effects were examined since they also contained both membrane-disrupting IMs and heat-generating AuNPs upon irradiation as physicotherapeutic agents. For the optimal enclosure of IMs containing hydrophilic drugs, a porous inner skeleton made of poly(lactic-co-glycolic acid) was introduced, which would play the roles of not only compartmentalizing the internal space but also enhancing proteolytic disintegration of the microcapsules to discharge and stabilize IMs to the outside. In fact, hydrophobic paclitaxel and hydrophilic doxorubicin showed markedly enhanced drug efficacy when delivered in the IM-containing microcapsules exhibiting the 'quantal' release of both drugs into the cells whose integrity could be also affected by the IMs. In addition, the remnants of αS-AuNP microcapsules produced via proteolysis also caused cell death through photothermal effect. The multifactorial microcapsules are therefore considered as a promising anti-cancer drug carrier capable of performing combinatorial selective and non-selective chemical and physical therapies to overcome tumor heterogeneity and drug resistance.

Poly(Propylene Carbonate)-Based Biodegradable and Environment-Friendly Materials for Biomedical Applications.

Poly(propylene carbonate) (PPC) is an emerging "carbon fixation" polymer that holds the potential to become a "biomaterial of choice" in healthcare owing to its good biocompatibility, tunable biodegradability and safe degradation products. However, the commercialization and wide application of PPC as a biomedical material are still hindered by its narrow processing temperature range, poor mechanical properties and hydrophobic nature. Over recent decades, several physical, chemical and biological modifications of PPC have been achieved by introducing biocompatible polymers, inorganic ions or small molecules, which can endow PPC with better cytocompatibility and desirable biodegradability, and thus enable various applications. Indeed, a variety of PPC-based degradable materials have been used in medical applications including medical masks, surgical gowns, drug carriers, wound dressings, implants and scaffolds. In this review, the molecular structure, catalysts for synthesis, properties and modifications of PPC are discussed. Recent biomedical applications of PPC-based biomaterials are highlighted and summarized.

Review of recent preclinical and clinical research on ligand-targeted liposomes as delivery systems in triple negative breast cancer therapy.

Triple-negative breast Cancer (TNBC) is one of the deadliest types, making up about 20% of all breast cancers. Chemotherapy is the traditional manner of progressed TNBC treatment; however, it has a short-term result with a high reversibility pace. The lack of targeted treatment limited and person-dependent treatment options for those suffering from TNBC cautions to be the worst type of cancer among breast cancer patients. Consequently, appropriate treatment for this disease is considered a major clinical challenge. Therefore, various treatment methods have been developed to treat TNBC, among which chemotherapy is the most common and well-known approach recently studied. Although effective methods are chemotherapies, they are often accompanied by critical limitations, especially the lack of specific functionality. These methods lead to systematic toxicity and, ultimately, the expansion of multidrug-resistant (MDR) cancer cells. Therefore, finding novel and efficient techniques to enhance the targeting of TNBC treatment is an essential requirement. Liposomes have demonstrated that they are an effective method for drug delivery; however, among a large number of liposome-based drug delivery systems annually developed, a small number have just received authorization for clinical application. The new approaches to using liposomes target their structure with various ligands to increase therapeutic efficiency and diminish undesired side effects on various body tissues. The current study describes the most recent strategies and research associated with functionalizing the liposomes' structure with different ligands as targeted drug carriers in treating TNBCs in preclinical and clinical stages.

Biomaterials in Drug Delivery: Advancements in Cancer and Diverse Therapies-Review.

Nano-sized biomaterials are innovative drug carriers with nanometric dimensions. Designed with biocompatibility in mind, they enable precise drug delivery while minimizing side effects. Controlled release of therapeutic substances enhances efficacy, opening new possibilities for treating neurological and oncological diseases. Integrated diagnostic-therapeutic nanosystems allow real-time monitoring of treatment effectiveness, which is crucial for therapy personalization. Utilizing biomaterials as nano-sized carriers in conjunction with drugs represents a promising direction that could revolutionize the field of pharmaceutical therapy. Such carriers represent groundbreaking drug delivery systems on a nanometric scale, designed with biocompatibility in mind, enabling precise drug delivery while minimizing side effects. Using biomaterials in synergy with drugs demonstrates significant potential for a revolutionary impact on pharmaceutical therapy. Conclusions drawn from the review indicate that nano-sized biomaterials constitute an innovative tool that can significantly improve therapy effectiveness and safety, especially in treating neurological and oncological diseases. These findings should guide researchers towards further studies to refine nano-sized biomaterials, assess their effectiveness under various pathological conditions, and explore diagnostic-therapeutic applications. Ultimately, these results underscore the promising nature of nano-sized biomaterials as advanced drug carriers, ushering in a new era in nanomedical therapy.

Sustainable Silk-Based Particulate Systems for the Controlled Release of Pharmaceuticals and Bioactive Agents in Wound Healing and Skin Regeneration.

The increasing demand for innovative approaches in wound healing and skin regeneration has prompted extensive research into advanced biomaterials. This review focuses on showcasing the unique properties of sustainable silk-based particulate systems in promoting the controlled release of pharmaceuticals and bioactive agents in the context of wound healing and skin regeneration. Silk fibroin and sericin are derived from well-established silkworm production and constitute a unique biocompatible and biodegradable protein platform for the development of drug delivery systems. The controlled release of therapeutic compounds from silk-based particulate systems not only ensures optimal bioavailability but also addresses the challenges associated with conventional delivery methods. The multifaceted benefits of silk proteins, including their inherent biocompatibility, versatility, and sustainability, are explored in this review. Furthermore, the intricate mechanisms by which controlled drug release takes place from silk-based carriers are discussed.

Xanthohumol-A Miracle Molecule with Biological Activities: A Review of Biodegradable Polymeric Carriers and Naturally Derived Compounds for Its Delivery.

Xanthohumol (Xn), a prenylated chalcone found in Hop (Humulus lupulus L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life. To address these drawbacks, researchers have made numerous attempts to improve its absorption, solubility, and bioavailability. Polymeric drug delivery systems (PDDSs) have experienced significant development over the last two decades. Polymeric drug delivery is defined as a formulation or device that allows the introduction of a therapeutic substance into the body. Biodegradable and bioreducible polymers are the ideal choice for a variety of new DDSs. Xn formulations based on biodegradable polymers and naturally derived compounds could solve some of the major drawbacks of Xn-based drug delivery. In this regard, the primary concern of this study is on presenting innovative formulations for Xn delivery, such as nanoparticles (NPs), nanomicelles, nanoliposomes, solid lipid nanoparticles (SLNs), and others, as well as the received in vitro and in vivo data. Furthermore, this work describes the chemistry and broad biological activity of Xn, which is particularly useful in modern drug technology as well as the cosmetics industry. It is also important to point out that the safety of using Xn, and its biotransformation, pharmacokinetics, and clinical applications, have been thoroughly explained in this review.