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Nanoparticle-based drug delivery systems hold great promise for improving the effectiveness of anti-tumor therapies. However, their clinical translation remains hindered by several significant challenges, including intricate preparation processes, limited drug loading capacity, and concerns regarding potential toxicity. In this context, pure drug-assembled nanosystems (PDANSs) have emerged as a promising alternative, attracting extensive research interest due to their simple preparation methods, high drug loading efficiency, and suitability for large-scale industrial production. This innovative approach presents new opportunities to enhance both the safety and therapeutic efficacy of cancer treatments. This review comprehensively explores recent progress in the application of PDANSs for cancer therapy. It begins by detailing the self-assembly mechanisms and fundamental principles underlying PDANS formation. The discussion then advances to strategies for assembling single pure drug nanoparticles, as well as the co-assembly of multiple drugs. Subsequently, the review addresses the therapeutic potential of PDANSs in combination treatment modalities, encompassing diagnostic and therapeutic applications. These include combinations of chemotherapeutic agents, phototherapeutic approaches, the integration of chemotherapy with phototherapy, and the synergistic use of immunotherapy with other treatment methods. Finally, the review highlights the potential of PDANSs in advancing tumor therapy and their prospects for clinical application, providing key insights for future research aimed at optimizing this technology and broadening its utility in cancer treatment. [ABSTRACT FROM AUTHOR]

Active components of natural products, which include paclitaxel, curcumin, gambogic acid, resveratrol, triptolide and celastrol, have promising anti-inflammatory, antitumor, anti-oxidant, and other pharmacological activities. However, their clinical application is limited due to low solubility, instability, low bioavailability, rapid metabolism, short half-life, and strong off-target toxicity. To overcome these drawbacks, cell membrane-based biomimetic nanosystems have emerged that avoid clearance by the immune system, enhance targeting, and prolong drug circulation, while also improving drug solubility and bioavailability, enhancing drug efficacy, and reducing side effects. This review summarizes recent advances in the preparation and coating of cell membrane-coated biomimetic nanosystems and in their applications to disease for targeted natural products delivery. Current challenges, limitations, and prospects in this field are also discussed, providing a research basis for the development of multifunctional biomimetic nanosystems for natural products. [ABSTRACT FROM AUTHOR]

In this work, the peculiarities of self-organization of patterned micro- and nanosystems under near-equilibrium condensation conditions were consistently considered. The criteria for stationarity of near-equilibrium condensation were introduced, and interrelations between the condensate local growth kinetics and the corresponding local technological parameters were described. Dissipative self-organization of small supersaturations in physically and chemically active medium-condensate systems were compared. The effectiveness of the unification of dissipative self-organization of small supersaturations and conservative self-organization of patterned micro- and nanosystems formation was shown, which forms the basis of a new concept of complete self-organized systems. [ABSTRACT FROM AUTHOR]

The design, synthesis and characterization of a novel nucleoamino acid derivative based on an l-tryptophanamide functionalised with a thymine nucleobase (named TrpT) is here described. The novel construct's tendency to self-assemble into supramolecular networks in aqueous solution was demonstrated by dynamic light scattering (DLS), circular dichroism (CD), fluorescence and UV spectroscopic measurements. TrpT nanoaggregates showed good stability (up to 5 h) at 140 µM and proved to comprise species of mean hydrodynamic diameter 330 nm and a homogeneous size distribution; scanning electron microscopy (SEM) analysis further revealed these to be spherical-shaped assemblies. The ability of TrpT nanoaggregates to bind curcumin, selected as a model anticancer drug, was also evaluated and its release was monitored over time by confocal microscopy. Molecular docking studies were performed on both TrpT self-assembly and curcumin-loaded nanoaggregates suggesting that the phytomolecule can be accommodated in the interior of the supramolecular network via hydrophobic (π−π and π-alkyl) interactions; the formation of TrpT-curcumin adducts may improve the polarity of the highly-hydrophobic curcumin with a resulting logP closer to the optimal values expected for a good drug bioavailability, as estimated by the ADMETlab software. Finally, the high stability of TrpT nanoassembly in human serum, and the absence of significant toxic effects on human model cells in a cell viability assay, were also demonstrated. Despite its thymine-based scaffold, TrpT was shown not to bind adenine-bearing nucleic acids, suggesting that this interaction is hindered by its intrinsic propensity to self-assemble in preference to forming A-T base pairings. Instead, TrpT was able to interact with a serum protein such as bovine serum albumin (BSA), known to improve the bloodstream transportation and bioavailability of its cargo. Collectively, our findings support the potential use of TrpT for the development of new drug delivery systems. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs), including leishmaniasis, trypanosomiasis, and schistosomiasis, impose a significant public health burden, especially in developing countries. Despite control efforts, treatment remains challenging due to drug resistance and lack of effective therapies. Objective: This study aimed to synthesize the current research on the combination therapy and phytochemical-loaded nanosystems, which have emerged as promising strategies to enhance treatment efficacy and safety. Methods/Results: In the present review, we conducted a systematic search of the literature and identified several phytochemicals that have been employed in this way, with the notable efficacy of reducing the parasite load in the liver and spleen in cases of visceral leishmaniasis, as well as lesion size in cutaneous leishmaniasis. Furthermore, they have a synergistic effect against Trypanosoma brucei rhodesiense rhodesain; reduce inflammation, parasitic load in the myocardium, cardiac hypertrophy, and IL-15 production in Chagas disease; and affect both mature and immature stages of Schistosoma mansoni, resulting in improved outcomes compared to the administration of phytochemicals alone or with conventional drugs. Moreover, the majority of the combinations studied demonstrated enhanced solubility, efficacy, and selectivity, as well as increased immune response and reduced cytotoxicity. Conclusions: These formulations appear to offer significant therapeutic benefits, although further research is required to validate their clinical efficacy in humans and their potential to improve treatment outcomes in affected populations. [ABSTRACT FROM AUTHOR]

Background/Objectives: Retinopathy of prematurity (ROP) is a severe condition primarily affecting premature infants with a gestational age (GA) of 30 weeks or less and a birth weight (BW) of 1500 g or less. The objective of this review is to examine the risk factors, pathogenesis, and current treatments for ROP, such as cryotherapy, laser photocoagulation, and anti-VEGF therapy, while exploring the limitations of these approaches. Additionally, this review evaluates emerging nanotherapeutic strategies to address these challenges, aiming to improve ROP management. Methods: A comprehensive literature review was conducted to gather data on the pathogenesis, traditional treatment methods, and novel nanotherapeutic approaches for ROP. This included assessing the efficacy and safety profiles of cryotherapy, laser treatment, anti-VEGF therapy, and nanotherapies currently under investigation. Results: Traditional treatments, while effective in reducing disease progression, exhibit limitations, including long-term complications, tissue damage, and systemic side effects. Nanotherapeutic approaches, on the other hand, have shown potential in offering targeted drug delivery with reduced systemic toxicity, improved ocular drug penetration, and sustained release, which could decrease the frequency of treatments and enhance therapeutic outcomes. Conclusions: Nanotherapies represent a promising advancement in ROP treatment, offering safer and more effective management strategies. These innovations could address the limitations of traditional therapies, reducing complications and improving outcomes for premature infants affected by ROP. Further research is needed to confirm their efficacy and safety in clinical practice. [ABSTRACT FROM AUTHOR]

Copyright of Advances in Biochemistry / Postepy Biochemii is the property of Polish Biochemical Society / Acta Biochimica Polonica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition. [ABSTRACT FROM AUTHOR]

Skin cancer is a high-incidence complex disease, representing a significant challenge to public health, with conventional treatments often having limited efficacy and severe side effects. Nanocarrier-based systems provide a controlled, targeted, and efficacious methodology for the delivery of therapeutic molecules, leading to enhanced therapeutic efficacy, the protection of active molecules from degradation, and reduced adverse effects. These features are even more relevant in dual-loaded nanosystems, with the encapsulated drug molecules leading to synergistic antitumor effects. This review examines the potential of improving the treatment of skin cancer through dual-loaded liposomal systems. The performed analysis focused on the characterization of the developed liposomal formulations' particle size, polydispersity index, zeta potential, encapsulation efficiency, drug release, and in vitro and/or in vivo therapeutic efficacy and safety. The combination of therapeutic agents such as doxorubicin, 5-fluorouracil, paclitaxel, cetuximab, celecoxib, curcumin, resveratrol, quercetin, bufalin, hispolon, ceramide, DNA, STAT3 siRNA, Bcl-xl siRNA, Aurora-A inhibitor XY-4, 1-Methyl-tryptophan, and cytosine–phosphate–guanosine anionic peptide led to increased and targeted anticancer effects, having relevant complementary effects as well, including antioxidant, anti-inflammatory, and immunomodulatory activities, all relevant in skin cancer pathophysiology. The substantial potential of co-loaded liposomal systems as highly promising for advancing skin cancer treatment is demonstrated. [ABSTRACT FROM AUTHOR]

Bone metastasis, a prevalent occurrence in primary malignant tumors, is often associated with a grim prognosis. The bone microenvironment comprises various coexisting cell types, working together in a coordinated manner. This dynamic microenvironment plays a pivotal role in the initiation and progression of bone metastases. While cancer therapies have made advancements, the available options for addressing bone metastases remain insufficient. The advent of nanotechnology has ushered in a new era for managing and preventing bone metastases because of the physicochemical and adaptable advantages of nanoplatforms. In this review, we make an introduction of the underlying mechanisms and the current clinical therapies of bone metastases, highlighting the advances of intelligent nanosystems that can stimulate vascular regeneration, promote bone regeneration, eliminate tumor cells, minimize bone damage, and expedite bone healing. The innovation surrounding bone-targeting nanoplatforms presents a fresh approach to the theranostics of bone metastases. Illustration of therapies for bone metastases [Display omitted] • The metastatic cascade and the vicious cycle of bone metastases are introduced. • The two-sided role of the bone microenvironment in bone metastases are discussed. • Emerging nanotherapeutics against bone metastases are summarized. • Challenges in using current nanotechnology to manage bone metastases are concluded. • Future frontiers in nanotherapy for bone metastases treatment are highlighted. [ABSTRACT FROM AUTHOR]

Periodontitis is one of the most common oral diseases. It is generally treated by non-surgical and/or surgical therapy with adjunctive approaches for prevention and control. The current understanding of the pathogenesis of periodontitis has unraveled the importance of the inflammatory and immune reactions to combat periodontitis whose etiology is an overlap of microbial, genetic, and environmental factors in a susceptible host. Based on this premise, many therapeutic modalities have been investigated or attempted to resolve this inflammatory disease. Amongst these, nanomedicine has been shown to have therapeutic applications in periodontitis, especially focused on immunomodulation because periodontitis is characterized by over-reactive immune response. This mini-review explores the potential of nanosystems in treating periodontitis by providing an overview of the research efforts in this field of therapeutics. The unique physicochemical and targeting properties of nanosystems seem to be potentially effective platforms for treating periodontitis.

There has been a growing curiosity and enthusiasm surrounding recent advancements in nanotechnology, electromagnetism, and optics. This interdisciplinary collaboration encompasses fields such as nanomaterials, nanoelectronics, and nanobiotechnology, which often overlap in their applications. One area that has attracted significant attention is the use of metal nanoparticles (MNPs), which has resulted in notable advancements in medicine. MNPs hold the promise of significantly boosting drug delivery efficacy, reducing unwanted side effects, and enhancing delivery precision. They also have applications in diagnostics, the development of biocompatible materials, and the exploration of nutraceuticals. Using metal nanoparticles in drug delivery provides benefits such as increased stability, prolonged circulation time, enhanced distribution, and precise targeting. The field of nanobiotechnnolgy has facilitated the creation of eco-friendly approaches, referred to as green synthesis, for the production of MNPs. MNPs offer improved stability and targeted release in drug delivery, while also providing a more sustainable alternative to chemical synthesis. This review aims to address the challenges and prospects of utilizing MNPs in drug delivery, with a specific focus on sustainable approaches for fabricating and modifying metal nanocarriers. It also explores the application of various MNPs in drug delivery systems (DDSs).

Jianlan Peng,1 Shiying Li,2 Huihui Ti1,3 1School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Guangdong Province Precise Medicine and Big Data Engineering Technology Research Center for Traditional Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Huihui Ti; Shiying Li, Email tihuihui@126.com; lisy-sci@gzhmu.edu.cnAbstract: Low immunogenicity of tumors poses a challenge in the development of effective tumor immunotherapy. However, emerging evidence suggests that certain therapeutic approaches, such as chemotherapy, radiotherapy, and phototherapy, can induce varying degrees of immunogenic cell death (ICD). This ICD phenomenon leads to the release of tumor antigens and the maturation of dendritic cells (DCs), thereby enhancing tumor immunogenicity and promoting immune responses. However, the use of a single conventional ICD inducer often fails to achieve in situ tumor ablation and establish long-term anti-tumor immune responses. Furthermore, the induction of ICD induction varies among different approaches, and the distribution of the therapeutic agent within the body influences the level of ICD and the occurrence of toxic side effects. To address these challenges and further boost tumor immunity, researchers have explored nanosystems as inducers of ICD in combination with tumor immunotherapy. This review examines the mechanisms of ICD and different induction methods, with a specific focus on the relationship between ICD and tumor immunity. The aim is to explore the research advancements utilizing various nanomaterials to enhance the body’s anti-tumor effects by inducing ICD. This paper aims to contribute to the development and clinical application of nanomaterial-based ICD inducers in the field of cancer immunotherapy by providing important theoretical guidance and practical references.Keywords: tumor immunotherapy, immunogenicity, ICD, DAMPs, nanosystems

The synergistic effect of antineoplastic drug co-encapsulation systems has made them highly regarded due to their improved pharmacological efficacy. Biopolymer-coated liposomes were evaluated for paclitaxel and doxorubicin co-encapsulation in MCF-7 and MDA-MB-231 breast cancer cell lines. These nanosystems are characterized by dynamic light scattering, transmission electron microscopy, and UV–VIS spectroscopy. The conventional and hybrid liposomal systems presented sizes of 150 to 230 nm and %EE greater than 80% for the encapsulated active ingredients. These drug-laden liposomal systems significantly decreased cell viability in both breast cancer cell lines compared with liposome-free drugs. The delivery of antineoplastic drugs in breast cancer therapy could potentially benefit from new hybrids for drug co-encapsulation. [ABSTRACT FROM AUTHOR]

There has been a growing curiosity and enthusiasm surrounding recent advancements in nanotechnology, electromagnetism, and optics. This interdisciplinary collaboration encompasses fields such as nanomaterials, nanoelectronics, and nanobiotechnology, which often overlap in their applications. One area that has attracted significant attention is the use of metal nanoparticles (MNPs), which has resulted in notable advancements in medicine. MNPs hold the promise of significantly boosting drug delivery efficacy, reducing unwanted side effects, and enhancing delivery precision. They also have applications in diagnostics, the development of biocompatible materials, and the exploration of nutraceuticals. Using metal nanoparticles in drug delivery provides benefits such as increased stability, prolonged circulation time, enhanced distribution, and precise targeting. The field of nanobiotechnnolgy has facilitated the creation of eco-friendly approaches, referred to as green synthesis, for the production of MNPs. MNPs offer improved stability and targeted release in drug delivery, while also providing a more sustainable alternative to chemical synthesis. This review aims to address the challenges and prospects of utilizing MNPs in drug delivery, with a specific focus on sustainable approaches for fabricating and modifying metal nanocarriers. It also explores the application of various MNPs in drug delivery systems (DDSs). [ABSTRACT FROM AUTHOR]

Copyright of Acta Materiae Compositae Sinica is the property of Acta Materiea Compositae Sinica Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms—including but not limited to liposomes, dendrimers, and micelles—have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology. [ABSTRACT FROM AUTHOR]

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments lacking efficiency and leading to severe side effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150 nm) and homogeneous (polydispersity index of 0.162) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models (inhibitory concentrations between 12.37 ng/mL and 14.72 ng/mL). Additionally, they also revealed substantial anti-inflammatory activity (inhibitory concentration of 28.98 ng/mL), effects complementary to direct antitumor activity. Niosome safety was also assessed, both in vitro (skin, liver, and kidney cells) and ex vivo (hen's egg chorioallantoic membrane), and results showed that compound encapsulation increased its safety. Hence, small, and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies. Future research should focus on evaluating the potential of the developed platform in in vivo models. [ABSTRACT FROM AUTHOR]

The co-delivery of paclitaxel (PTX) and curcumin (Cur) has proven to be an effective method for breast cancer treatment. However, the poor solubility of both PTX and Cur limits their bioavailability, resulting in insufficient anticancer effects. Herein, we developed a novel nanogel based on fucoidan to facilitate the co-encapsulation of PTX and Cur and improve their therapeutic effectiveness. The thermosensitive copolymer, fucoidan-pluronic F127 (Fud-F127), was synthesized and characterized by various techniques, including proton nuclear magnetic resonance (1H-NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), and critical micelle concentration (CMC). Cur and PTX were easily loaded into the Fud-F127 nanogel (Fud-F127@Cur@PTX), with high drug loading capacity of 84.4% for Cur and 86.83% for PTX. The PTX and Cur were sustainedly released followed a Fickian diffusion mechanism and triggered at acidic pH 5.5. In vitro assessments demonstrated that Fud-F127@Cur@PTX exhibited lower cytotoxicity towards breast cancer cells (MCF-7) than Fud-F127@PTX and free PTX at the same dose, highlighting the potential of Cur in mitigating the acute toxicity of PTX. These results suggest the potential of Fud-F127 as an effective nanocarrier for the co-delivery of PTX and Cur, which aims to minimize the adverse effects associated with breast cancer treatment. Fud-F127 nanogel system encapsulating Cur and PTX for enhanced delivery [ABSTRACT FROM AUTHOR]

Copyright of Buletinul AGIR is the property of Asociatia Generala a Inginerilor din Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To control hypertension, long-term continuous antihypertensive therapeutics are required and five classes of antihypertensive drugs are frequently involved, including diuretics, β-blockers, calcium channel blockers, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors. Although with demonstrated clinical utility, there is still room for the improvement of many antihypertensive drugs in oral tablet or capsule dosage form, in terms of reducing systemic side effects and first-pass hepatic drug uptake. Meanwhile, nanocarrier-mediated transdermal drug delivery systems have emerged as a powerful tool for various disease treatments. With benefits such as promoting patient compliance for long-time administration, enhancing skin permeability, and reducing systemic side effects, these systems are reasonably investigated and developed for the transdermal delivery of multiple antihypertensive drugs. This review aims to summarize the literature relating to nanosystem-based transdermal antihypertensive drug delivery and update recent advances in this field, as well as briefly discuss the challenges and prospects of engineering transdermal delivery nanosystems for hypertension treatment. [ABSTRACT FROM AUTHOR]

In this work, the peculiarities of self-organization of patterned micro- and nanosystems under near-equilibrium condensation conditions were consistently considered. The criteria for stationarity of near-equilibrium condensation were introduced, and interrelations between the condensate local growth kinetics and the corresponding local technological parameters were described. Dissipative self-organization of small supersaturations in physically and chemically active medium-condensate systems were compared. The effectiveness of the unification of dissipative self-organization of small supersaturations and conservative self-organization of patterned micro- and nanosystems formation was shown, which forms the basis of a new concept of complete self-organized systems.

Abstract The main objective of this study was to optimize the fermentation process using Serratia sp. BR13816, a bacterial isolate from Amazonian soil, and to evaluate the formation of nanoemulsions. Submerged fermentation was carried out with different carbon and nitrogen sources. Based on the emulsification index and surface tension results, we selected a hydrophobic (corn oil) and a hydrophilic (glycerol) carbon source, and a nitrogen one (urea). For fermentation using corn oil/urea greater emulsification indexes and lower surface tensions were verified at pH 8, 25 °C, and 48 h, whereas for glycerol/urea-supplemented medium the best conditions were attained at pH 7, 30 °C, and 96 h. These pre-selected factors (pH, temperature, and time) were used in a central composite rotatable design (CCRD) for an additional fermentation optimization of the two carbon/nitrogen mediums, corn oil/urea and glycerol/urea. The two best nutritional systems based on corn oil/urea and glycerol/urea were selected using a central composite rotatable design (CCRD). The mathematical models using the response surface methodology showed adequate adjustment. The best run of the experimental design for corn oil/urea (6.00% /0.60%) and glycerol/urea (3.00% /1.40%) systems presented surface tension values of 35.70 mN/m and 37.10 mN/m, respectively. The nanoemulsions produced by a low-energy method presented average sizes by dynamic light scattering varying from 453.1 nm to 667.3 nm when 0.1% of the oil was employed. Therefore, Serratia sp. BR13816 showed promising biosurfactant-producing potential for future industrial applications.

Sulfur dioxide (SO 2), long considered to be a harmful atmospheric pollutant, has recently been posited as the fourth gasotransmitter, as it is produced endogenously in mammals and has important pathophysiological effects. The field of tumor therapy has witnessed a paradigm shift with the emergence of SO 2 -based gas therapy. This has been possible because SO 2 is a potent glutathione consumer that can promote the production of reactive oxygen species, eventually leading to oxidative-stress-induced cancer cell death. Nevertheless, this therapeutic gas cannot be directly administrated in gaseous form. Thus, various nano formulations incorporating SO 2 donors or prodrugs capable of storing and releasing SO 2 have been developed in an attempt to achieve active/passive intratumoral accumulation and SO 2 release in the tumor microenvironment. In this review article, the advances over the past decade in nanoplatforms incorporating sulfur SO 2 prodrugs to provide controlled release of SO 2 for cancer therapy are summarized. We first describe the synthesis of polypeptide SO 2 prodrugs to overcome multiple drug resistance that was pioneered by our group, followed by other macromolecular SO 2 prodrug structures that self-assemble into nanoparticles for tumor therapy. Second, we describe nanoplatforms composed of various small-molecule SO 2 donors with endogenous or exogenous stimuli responsiveness, including thiol activated, acid-sensitive, and ultraviolet or near-infrared light-responsive SO 2 donors, which have been used for tumor inhibition. Combinations of SO 2 gas therapy with photodynamic therapy, chemotherapy, photothermal therapy, sonodynamic therapy, and nanocatalytic tumor therapy are also presented. Finally, we discuss the current limitations and challenges and the future outlook for SO 2 -based gas therapy. Gas therapy is attracting increasing attention in the scientific community because it is a highly promising strategy against cancer owing to its inherent biosafety and avoidance of drug resistance. Sulfur dioxide (SO 2) is recently found to be produced endogenously in mammals with important pathophysiological effects. This review summarizes recent advances in SO 2 releasing nanosystems for cancer therapy, including polymeric prodrugs, endogenous or exogenous stimulus-activated SO 2 donors delivered by nanoplatform and combination therapy strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Polysaccharide-based nanosystem is an umbrella term for many areas within research and technology dealing with polysaccharides that have at least one of their dimensions in the realm of a few hundreds of nanometers. Nanoparticles, nanocrystals, nanofibers, nanofilms, and nanonetworks can be fabricated from many different polysaccharide resources. Abundance in nature, cellulose, starch, chitosan, and pectin of different molecular structures are widely used to fabricate nanosystems for versatile industrial applications. This review presents the dissolution and modification of polysaccharides, which are influenced by their different molecular structures and applications. The dissolution ways include conventional organic solvents, ionic liquids, inorganic strong alkali and acids, enzymes, and hydrothermal treatment. Rheological properties of polysaccharide-based nano slurries are tailored for the purpose functions of the final products, e.g., imparting electrostatic functions of nanofibers to reduce viscosity by using lithium chloride and octenyl succinic acid to increase the hydrophobicity. Nowadays, synergistic effects of polysaccharide blends are increasingly highlighted. In particular, the reinforcing effect of nanoparticles, nanocrystals, nanowhiskers, and nanofibers to hydrogels, aerogels, and scaffolds, and the double network hydrogels of a rigid skeleton and a ductile substance have been developed for many emerging issues. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR's biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice. [ABSTRACT FROM AUTHOR]

The existence of the blood-brain barrier (BBB) restricts the entry of drugs from the circulation into the central nervous system (CNS), which severely affects the treatment of neurological diseases, including glioblastoma, Parkinson's disease (PD), and Alzheimer's disease (AD). With the advantage of bypassing the BBB and avoiding systemic distribution, intranasal administration has emerged as an alternative method of delivering drugs to the brain. Drug delivery directly to the brain using intranasal nanosystems represents a new paradigm for neurological disease treatment because of its advantages in improving drug solubility and stability in vivo, enabling targeted drug delivery and controlled release, and reducing non-specific toxicity. And it has shown efficacy in animal models and clinical applications. Herein, this review describes the mechanisms of intranasal delivery of brain-targeted drugs, the properties of nanosystems for intranasal administration (e.g., liposomes, nanoemulsions, and micelles), and strategies for intranasal drug delivery to enhance brain-targeted drug delivery. Recent applications of nanosystems in intranasal drug delivery and disease treatment have been comprehensively reviewed. Although encouraging results have been reported, significant challenges still need to be overcome to translate these nanosystems into clinics. Therefore, the future prospects of intranasal drug delivery nanosystems are discussed in depth, expecting to provide useful insights and guidance for effective neurological disease treatment. [ABSTRACT FROM AUTHOR]

Cancer continues to pose a significant global health obstacle, requiring the development of novel approaches in medicine administration to address its intricate nature. The Tumor Micro-Environment (TME) poses a substantial barrier to the successful delivery of drugs, often impeding drug diffusion and restricting therapeutic efficacy. Developing sizetunable drug delivery nanosystems has emerged as a viable approach, potentially boosting drug delivery efficiency. This study article explores the advancement of Smart Size-Tunable Drug Delivery Nanosystems (S2TD2-NS) and the manipulation of the tumor microenvironment to enhance drug penetration at greater depths. The drug delivery platform S2TD2-NS utilizes the distinctive characteristics of (R)-(+)-α-Lipoic Acid to enhance drug encapsulation, resulting in a highly effective drug delivery system. The study's findings demonstrate a mean encapsulation effectiveness of 89.33%, a fluorescence intensity ratio 1.33, a decrease in tumor volume to 722.88 mm³, and a minimal heat production at 37.6°C. The S2TD2-NS technology provides a promising way to mitigate existing constraints in drug delivery, hence opening new opportunities for developing enhanced cancer therapy techniques [ABSTRACT FROM AUTHOR]

Solid-lipid nanoparticles (SLNs) are an innovative group of nanosystems used to deliver medicine to their respective targets with better efficiency and bioavailability in contrast to classical formulations. SLNs are less noxious, have fewer adverse effects, have more biocompatibility, and have easy biodegradability. Lipophilic, hydrophilic and hydrophobic drugs can be loaded into SLNs, to enhance their physical and chemical stability in critical environments. Certain antifungal agents used in different treatments are poorly soluble medications, biologicals, proteins etc. incorporated in SLNs to enhance their therapeutic outcome, increase their bioavailability and target specificity. SLNs-based antifungal agents are currently helpful against vicious drug-resistant fungal infections. This review covers the importance of SLNs in drug delivery of classical antifungal drugs, historical background, preparation, physicochemical characteristic, structure and sizes of SLNs, composition, drug entrapment efficacy, clinical evaluations and uses, challenges, antifungal drug resistance, strategies to overcome limitations, novel antifungal agents currently in clinical trials with special emphasis on fungal infections.

The synergistic effect of antineoplastic drug co-encapsulation systems has made them highly regarded due to their improved pharmacological efficacy. Biopolymer-coated liposomes were evaluated for paclitaxel and doxorubicin co-encapsulation in MCF-7 and MDA-MB-231 breast cancer cell lines. These nanosystems are characterized by dynamic light scattering, transmission electron microscopy, and UV–VIS spectroscopy. The conventional and hybrid liposomal systems presented sizes of 150 to 230 nm and %EE greater than 80% for the encapsulated active ingredients. These drug-laden liposomal systems significantly decreased cell viability in both breast cancer cell lines compared with liposome-free drugs. The delivery of antineoplastic drugs in breast cancer therapy could potentially benefit from new hybrids for drug co-encapsulation.

Spinal cord injury (SCI) is a debilitating condition with limited treatment options, necessitating the exploration of innovative regenerative approaches. Nanosystems have emerged as promising tools for neural tissue engineering and drug delivery in SCI. This review provides a concise overview of the current progress and future directions in nanosystems-enabled regenerative therapies for SCI. It highlights the underlying mechanisms of SCI, including pathophysiology, inflammatory response, and axonal degeneration. Various nanosystems, such as nanoparticles and nano-scaffolds, are discussed for their potential in promoting neural tissue regeneration, neuroprotection, and controlled drug delivery. Additionally, the challenges of clinical translation, safety considerations, and regulatory aspects are addressed, along with the assessment of biocompatibility and adverse effects. This review highlights the immense potential of nanosystems in SCI treatment and emphasizes the need for further research to overcome remaining hurdles and facilitate their clinical implementation.

The growing number of infections caused by multidrug-resistant bacterial strains, limited treatment options, multi-species infections, high toxicity of the antibiotics used, and an increase in treatment costs are major challenges for modern medicine. To remedy this, scientists are looking for new antibiotics and treatment methods that will effectively eradicate bacteria while continually developing different resistance mechanisms. Ceragenins are a new group of antimicrobial agents synthesized based on molecular patterns that define the mechanism of antibacterial action of natural antibacterial peptides and steroid-polyamine conjugates such as squalamine. Since ceragenins have a broad spectrum of antimicrobial activity, with little recorded ability of bacteria to develop a resistance mechanism that can bridge their mechanism of action, there are high hopes that this group of molecules can give rise to a new family of drugs effective against bacteria resistant to currently used antibiotics. Experimental data suggests that core-shell nanosystems, in which ceragenins are presented to bacterial cells on metallic nanoparticles, may increase their antimicrobial potential and reduce their toxicity. However, studies should be conducted, among others, to assess potential long-term cytotoxicity and in vivo studies to confirm their activity and stability in animal models. Here, we summarized the current knowledge on ceragenins and ceragenin-containing nanoantibiotics as potential new tools against emerging Gram-negative rods associated with nosocomial infections. [ABSTRACT FROM AUTHOR]

The high water and nutritional contents of meat and fish products make them susceptible to spoilage. Thus, one of the most important challenges faced by the meat industry is extending the shelf life of meat and fish products. In recent years, increasing concerns associated with synthetic compounds on health have limited their application in food formulations. Thus, there is a great need for natural bioactive compounds. Direct use of these compounds in the food industry has faced different obstacles due to their hydrophobic nature, high volatility, and sensitivity to processing and environmental conditions. Nanotechnology is a promising method for overcoming these challenges. Thus, this article aims to review the recent knowledge about the effect of biopolymer-based edible films or coatings on the shelf life of meat and fish products. This study begins by discussing the effect of biopolymer (pectin, alginate, and chitosan) based edible films or coatings on the oxidation stability and microbial growth of meat products. This is followed by an overview of the nano-encapsulation systems (nano-emulsions and nanoliposomes) and the effect of edible films or coatings incorporated with nanosystems on the shelf life of meat and fish products. [ABSTRACT FROM AUTHOR]

Microbial biofilm formation on implantable devices causes chronic infections that cannot be treated with existing antimicrobials. Quorum sensing inhibitors (QSIs) have recently emerged as novel antimicrobials for the prevention of biofilm formation. But blocking QS alone is insufficient to inhibit biofilm‐associated chronic infections. Herein, chitosan hollow nanospheres are capped by bacteria‐responsive β‐casein to form a synergistic antifouling nanosystem consisting of a QSI and bactericide. β‐casein is degraded by protease in a bacteria‐colonized microenvironment in situ thus, QSI and bactericide are released sequentially. The release of QSI sensitises bacteria effectively through reduction of surface hydrophobicity, eDNA content, and lipopolysaccharide production in biofilms, amplifying the chemotherapeutic action of the bactericide. Compared to the uncoated surface, the coated surface inhibits biofilm formation and removes preformed biofilms of Pseudomonas aeruginosa PAO1 and methicillin‐resistant Staphylococcus aureus by 1.8 logs and 1.9 logs of biomass inhibition, respectively. The coated catheters are found to stay clean for 30 days under artificial urine flow, while the uncoated catheters are clogged by bacterial biofilms within 5 days. Finally, the long term antifouling activity in vivo is confirmed. Overall, the nanosystem is devoted to making urinary catheters resistant to bacterial biofilm formation for the long term. [ABSTRACT FROM AUTHOR]

Solid-lipid nanoparticles (SLNs) are an innovative group of nanosystems used to deliver medicine to their respective targets with better efficiency and bioavailability in contrast to classical formulations. SLNs are less noxious, have fewer adverse effects, have more biocompatibility, and have easy biodegradability. Lipophilic, hydrophilic and hydrophobic drugs can be loaded into SLNs, to enhance their physical and chemical stability in critical environments. Certain antifungal agents used in different treatments are poorly soluble medications, biologicals, proteins etc. incorporated in SLNs to enhance their therapeutic outcome, increase their bioavailability and target specificity. SLNs-based antifungal agents are currently helpful against vicious drug-resistant fungal infections. This review covers the importance of SLNs in drug delivery of classical antifungal drugs, historical background, preparation, physicochemical characteristic, structure and sizes of SLNs, composition, drug entrapment efficacy, clinical evaluations and uses, challenges, antifungal drug resistance, strategies to overcome limitations, novel antifungal agents currently in clinical trials with special emphasis on fungal infections. [ABSTRACT FROM AUTHOR]

The usage of nanotechnology in the fight against parasitic diseases is in the early stages of development, but it brings hopes that this new field will provide a solution to target the early stages of parasitosis, compensate for the lack of vaccines for most parasitic diseases, and also provide new treatment options for diseases in which parasites show increased resistance to current drugs. The huge physicochemical diversity of nanomaterials developed so far, mainly for antibacterial and anti-cancer therapies, requires additional studies to determine their antiparasitic potential. When designing metallic nanoparticles (MeNPs) and specific nanosystems, such as complexes of MeNPs, with the shell of attached drugs, several physicochemical properties need to be considered. The most important are: size, shape, surface charge, type of surfactants that control their dispersion, and shell molecules that should assure specific molecular interaction with targeted molecules of parasites' cells. Therefore, it can be expected that the development of antiparasitic drugs using strategies provided by nanotechnology and the use of nanomaterials for diagnostic purposes will soon provide new and effective methods of antiparasitic therapy and effective diagnostic tools that will improve the prevention and reduce the morbidity and mortality caused by these diseases. [ABSTRACT FROM AUTHOR]

AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences that can adopt a G-quadruplex (G4) structure and target nucleolin (NCL), a protein that acts as a co-receptor for several growth factors. Hence, this study aimed to characterize the AT11-L0 G4 structure and its interaction with several ligands for NCL targeting and to evaluate their capacity to inhibit angiogenesis using an in vitro model. The AT11-L0 aptamer was then used to functionalize drug-associated liposomes to increase the bioavailability of the aptamer-based drug in the formulation. Biophysical studies, such as nuclear magnetic resonance, circular dichroism, and fluorescence titrations, were performed to characterize the liposomes functionalized with the AT11-L0 aptamer. Finally, these liposome formulations with the encapsulated drugs were tested on the human umbilical vein endothelial cell (HUVEC) model to assess their antiangiogenic capacity. The results showed that the AT11-L0 aptamer–ligand complexes are highly stable, presenting melting temperatures from 45 °C to 60 °C, allowing for efficient targeting of NCL with a KD in the order of nM. The aptamer-functionalized liposomes loaded with ligands C8 and dexamethasone did not show cytotoxic effects in HUVEC cells compared with the free ligands and AT11-L0, as assessed by cell viability assays. AT11-L0 aptamer-functionalized liposomes encapsulating C8 and dexamethasone did not present a significant reduction in the angiogenic process when compared with the free ligands. In addition, AT11-L0 did not show anti-angiogenic effects at the concentrations tested. However, C8 shows potential as an angiogenesis inhibitor, which should be further developed and optimized in future experiments. [ABSTRACT FROM AUTHOR]

The nervous and immune systems go hand in hand in causing inflammation and pain. However, the two are not mutually exclusive. While some diseases cause inflammation, others are caused by it. Macrophages play an important role in modulating inflammation to trigger neuropathic pain. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has a well-known ability to bind with the cluster of differentiation 44 (CD44) receptor on classically activated M1 macrophages. Resolving inflammation by varying the molecular weight of HA is a debated concept. HA-based drug delivery nanosystems such as nanohydrogels and nanoemulsions, targeting macrophages can be used to relieve pain and inflammation by loading antinociceptive drugs and enhancing the effect of anti-inflammatory drugs. This review will discuss the ongoing research on HA-based drug delivery nanosystems regarding their antinociceptive and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Globally, Cancer therapy is still a major issue. With the latest developments in nanotechnology, layered double hydroxide (LDH)-based nanosystems are receiving special attention due to their pH dependent biodegradability, superior biocompatibility, easy surface modification, anion exchange capacity and high chemical stability, giving rise to great potential for cancer therapy. By intercalating inorganic, organic, or bio molecules into their lamellar lattice, new hybrid materials with dual or multi-functional features, including anticancer capabilities, can be developed from layered double hydroxide (LDH). Despite the fact that outstanding research has been published, few review papers address these essential and promising discoveries to stimulate the ongoing development of LDH-based nanosystems in the field of cancer therapy. This paper therefore study focuses on the most recent advancements in LDH-based chemotherapeutic nanosystems for cancer treatment. The information utilized in this review was gathered from studies that have previously been published and were retrieved from several Journal outlets. These reports dealt with the usage of layered doubled hydroxide-based chemotherapeutic nanosystems for the treatment of cancer. The research demonstrates that layered double hydroxides may be utilized to develop single or composite nanosystems that distribute therapeutic components precisely without causing cumulative damage for the field of nanomedicine. [ABSTRACT FROM AUTHOR]

Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration, respectively. Nevertheless, treatment is usually given through the oral route, but the low permeability of the blood–brain barrier reduces the amount of drug that will be able to reach it, thus consequently reducing the therapeutic efficacy. Which is why it is imperative to find new solutions to make these treatments more effective, safer, and faster. To overcome this obstacle, three main strategies have been used to improve brain drug targeting: the intranasal route of administration, which allows the drug to be directly transported to the brain by neuronal pathways, bypassing the blood–brain barrier and avoiding the hepatic and gastrointestinal metabolism; the use of nanosystems for drug encapsulation, including polymeric and lipidic nanoparticles, nanometric emulsions, and nanogels; and drug molecule functionalization by ligand attachment, such as peptides and polymers. Pharmacokinetic and pharmacodynamic in vivo studies' results have shown that intranasal administration can be more efficient in brain targeting than other administration routes, and that the use of nanoformulations and drug functionalization can be quite advantageous in increasing brain–drug bioavailability. These strategies could be the key to future improved therapies for depressive and anxiety disorders. [ABSTRACT FROM AUTHOR]

Nanotechnology-based strategies have played a pivotal role in innovative products in different technological fields, including medicine, agriculture, and engineering. The redesign of the nanometric scale has improved drug targeting and delivery, diagnosis, water treatment, and analytical methods. Although efficiency brings benefits, toxicity in organisms and the environment is a concern, particularly in light of global climate change and plastic disposal in the environment. Therefore, to measure such effects, alternative models enable the assessment of impacts on both functional properties and toxicity. Caenorhabditis elegans is a nematode model that poses valuable advantages such as transparency, sensibility in responding to exogenous compounds, fast response to perturbations besides the possibility to replicate human disease through transgenics. Herein, we discuss the applications of C. elegans to nanomaterial safety and efficacy evaluations from one health perspective. We also highlight the directions for developing appropriate techniques to safely adopt magnetic and organic nanoparticles, and carbon nanosystems. A description was given of the specifics of targeting and treatment, especially for health purposes. Finally, we discuss C. elegans potential for studying the impacts caused by nanopesticides and nanoplastics as emerging contaminants, pointing out gaps in environmental studies related to toxicity, analytical methods, and future directions. [ABSTRACT FROM AUTHOR]

[Display omitted] The evolution of sophisticated nanosystems has revolutionized biomedicine, notably in treating neurodegenerative diseases and cancer. These systems show potential in delivering medication precisely to affected tissues, improving treatment effectiveness while minimizing side effects. Nevertheless, a major hurdle in targeted drug delivery is breaching the blood–brain barrier (BBB), a selective shield separating the bloodstream from the brain and spinal cord. The tight junctions between endothelial cells in brain capillaries create a formidable physical barrier, alongside efflux transporters that expel harmful molecules. This presents a notable challenge for brain drug delivery. Nanosystems present distinct advantages in overcoming BBB challenges, offering enhanced drug efficacy, reduced side effects, improved stability, and controlled release. Despite their promise, challenges persist, such as the BBB's regional variability hindering uniform drug distribution. Efflux transporters can also limit therapeutic agent efficacy, while nanosystem toxicity necessitates rigorous safety evaluations. Understanding the long-term impact of nanomaterials on the brain remains crucial. Additionally, addressing nanosystem scalability, cost-effectiveness, and safety profiles is vital for widespread clinical implementation. This review delves into the advancements and obstacles of advanced nanosystems in targeted drug delivery for neurodegenerative diseases and cancer therapy, with a focus on overcoming the BBB. [ABSTRACT FROM AUTHOR]

Drug delivery nanosystems (DDnS) is widely developed recently. Gelatin is a high-potential biomaterial originated from natural resources for anticancer DDnS, which can effectively improve the utilization of anticancer drugs and reduce side effects. The hydrophilic, amphoteric behavior and sol-gel transition of gelatin can be used to fulfill various requirements of anticancer DDnS. Additionally, the high number of multifunctional groups on the surface of gelatin provides the possibility of crosslinking and further modifications. In this review, we focus on the properties of gelatin and briefly elaborate the correlation between the properties and anticancer DDnS. Furthermore, we discuss the applications of gelatin-based DDnS in various cancer treatments. Overall, we have summarized the excellent properties of gelatin and correlated with DDnS to provide a manual for the design of gelatin-based materials for DDnS.

Orally administered antipsychotic drugs are the first-line treatment for psychotic disorders, such as schizophrenia and bipolar disorder. Nevertheless, adverse drug reactions jeopardize clinical outcomes, resulting in patient non-compliance. The design formulation strategies for enhancing brain drug delivery has been a major challenge, mainly due to the restrictive properties of the blood–brain barrier. However, recent pharmacokinetic and pharmacodynamic in vivo assays confirmed the advantage of the intranasal route when compared to oral and intravenous administration, as it allows direct nose-to-brain drug transport via neuronal pathways, reducing systemic side effects and maximizing therapeutic outcomes. In addition, the incorporation of antipsychotic drugs into nanosystems such as polymeric nanoparticles, polymeric mixed micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanoemulgels, nanosuspensions, niosomes and spanlastics, has proven to be quite promising. The developed nanosystems, having a small and homogeneous particle size (ideal for nose-to-brain delivery), high encapsulation efficiency and good stability, resulted in improved brain bioavailability and therapeutic-like effects in animal models. Hence, although it is essential to continue research in this field, the intranasal delivery of nanosystems for the treatment of schizophrenia, bipolar disorder and other related disorders has proven to be quite promising, opening a path for future therapies with higher efficacy. [ABSTRACT FROM AUTHOR]