Uncovering proteome variations and concomitant quality changes of differently drying-treated rape (Brassica napus) bee pollen by label-free quantitative proteomics.

High moisture content of fresh bee pollen makes it difficult to preserve and thus makes drying a necessary process during the bee pollen production. Drying treatment will affect its quality and the effects of sun drying, hot-air drying and freeze drying on the proteome of rape (Brassica napus) bee pollen have been evaluated using label-free quantitative proteomics by liquid chromatography-tandem mass spectrometer (LC-MS/MS). A total of 8377 proteins are identified, among which the most abundant differential proteins were found in freeze drying-treated samples. Also freeze-drying treatment maximizes the content of antioxidant, antibacterial and anemic bioactive pollen protein. Besides, rape bee pollen is found to adjust its metabolism to protect itself during the drying process. These results can be favorable to evaluate the effects of drying treatment on the nutrition and function of processed rape bee pollen and insight into how rape bee pollen proteins respond to dehydration.

Water-ultrastable perovskite CsPbBr3 nanocrystals tailored by surface-confined strategy for amaranth sensing in food samples.

A vital challenge is to develop water-stable perovskite nanocrystals owing to the easy attack of its surface vacancy defects by water-molecule. Here, a facile surface-passivated strategy to dramatically improve the chem-stability and luminescent efficiency (LE) of the CsPbBr3 nanocrystals (CPB) is proposed, where sodium dodecyl sulfate (SDS) encapsulate on CPB, generating confined environment (named SDS@CPB). The flexible long carbon-chain of SDS can confine the movement of CPB to form an externally hydrophobic closed-shell and internally structural rigidity through the hydrophobic association between surface hydrophobic groups, improving the LE and maintaining long-term composition of CPB. While the sulfate group in SDS can reduce the surface-defects exposure of CPB through the coordination with Pb2+, inhibiting the invasion of water-molecule. Importantly, an SDS@CPB-based sensor was fabricated to detect amaranth in food samples with a lower detection limit (5.43 nM), which opens a new avenue for food sensing based on high-efficiency perovskite nanocrystals.

A new approach to detecting sugar syrup addition to honey: Stable isotope analysis of hexamethylenetetramine synthesised from honey monosaccharides (fructose and glucose).

One of the most common types of adulteration of honey involves the addition of invert sugar syrups. A new method was developed to measure the stable isotope ratios of carbon and carbon-bound non-exchangeable (CBNE) hydrogen from specific molecular positions in fructose and glucose in honey. This was achieved through periodate oxidation of the sugars to produce formaldehyde, followed by reaction with ammonia to form hexamethylenetetramine (HMT). The preparation was simplified, optimized, and validated by isotopic analysis of replicate syntheses of HMT from fructose, glucose, sugar syrup and a representative authentic honey sample. The optimized method had a repeatability standard deviation from 1.5‰ to 3.0‰ and from 0.1‰ to 0.4‰ for δ2H and δ13C, respectively. This methodology has advantages over alternative isotopic methods, for measuring CBNE hydrogen isotope ratios in sugars, in terms of time, sensitivity and operability and offers a complementary method to differentiate authentic honey from invert sugar syrups.

Whey protein isolate-resveratrol complex as a radical scavenging foaming ingredient with increased ultraviolet stability.

Functional foaming food ingredients play a vital role in preparing healthcare foods, however, the weak foamability and low photostability of ingredients severely limit their further development. Herein, whey protein isolate-resveratrol complexes (WPI-RES) were fabricated to address these challenges. Multi-spectral analysis and molecular simulation results revealed the key driving forces of hydrogen bonding and hydrophobic interactions to promote the formation of WPI-RES complexes, leading to the enhanced foamability and emulsifying properties of WPI after binding with RES. Importantly, the robust radical scavenging activity of RES within WPI was maintained under UV light irradiation compared to that of free RES as identified by DPPH assay, which was presumably due to inhibited photoisomerization of RES after binding to WPI. This work provides a promising foaming ingredient with increased ultraviolet stability and radical scavenging activity, paves the way to develop stable health-promoting foaming food products.

The dynamic change of flavor characteristics in Pacific oyster (Crassostrea gigas) during depuration uncovered by mass spectrometry-based metabolomics combined with gas chromatography-ion mobility spectrometry (GC-IMS).

The flavor of Pacific oyster (Crassostrea gigas) significantly changed during the depuration process. This work aimed to explore the mechanism of flavor changes during the 72 h depuration by metabolomics combined with gas chromatography-ion mobility spectrometry (GC-IMS). The metabolomics analysis indicated that carbohydrate metabolism was more affected in the early stage of depuration, including the citrate cycle, glyoxylae and dicarboxylate metabolism, etc. After 72 h depuration, it affected mainly the metabolism of global and overview maps and nucleoside metabolism, etc. The equivalent umami concentration (EUC) value was calculated and exhibited a gradual increase following a 48 h depuration. The GC-MS results revealed that the content of furans was the highest, and the content of aldehydes, ketones, and alcohols was the lowest after 48 h depuration, while the content of aldehydes, ketones, and alcohols increased after 72 h depuration. All these results suggested the depuration period was recommended to be controlled within 48 h.

Instant trachea reconstruction using 3D-bioprinted C-shape biomimetic trachea based on tissue-specific matrix hydrogels.

Currently, 3D-bioprinting technique has emerged as a promising strategy to offer native-like tracheal substitutes for segmental trachea reconstruction. However, there has been very limited breakthrough in tracheal repair using 3D-bioprinted biomimetic trachea owing to the lack of ideal bioinks, the requirement for precise structural biomimicking, and the complexity of multi-step surgical procedures by mean of intramuscular pre-implantation. Herein, we propose a one-step surgical technique, namely direct end-to-end anastomosis using C-shape 3D-bioprinted biomimetic trachea, for segmental trachea defect repair. First, two types of tissue-specific matrix hydrogels were exploited to provide mechanical and biological microenvironment conducive to the specific growth ways of cartilage and fibrous tissue respectively. In contrast to our previous O-shape tracheal design, the tubular structure of alternating C-shape cartilage rings and connecting vascularized-fibrous-tissue rings was meticulously designed for rapid 3D-bioprinting of tracheal constructs with optimal printing paths and models. Furthermore, in vivo trachea regeneration in nude mice showed satisfactory mechanical adaptability and efficient physiological regeneration. Finally, in situ segmental trachea reconstruction by direct end-to-end anastomosis in rabbits was successfully achieved using 3D-bioprinted C-shape biomimetic trachea. This study demonstrates the potential of advanced 3D-bioprinting for instant and efficient repair of segmental trachea defects.

Recent Excavation of Nanoethosomes in Current Drug Delivery.

In the current era, the Transdermal delivery of bioactive molecules has become an area of research interest. The transdermal route of administration enables direct entry of bioactive molecules into the systemic circulation with better and easy accessibility, bypassing the hepatic metabolism and improving patient compliance. Permeation through the skin has always been a barrier. To overcome this challenge, an efficient route by the vesicular system has been adopted so as to have better skin permeation of the bioactive molecules. A novel vesicular and non-invasive drug delivery system called Nanoethosomes was developed. Nanoethosomes are lipid-based vesicular carriers that are used for deeper permeation of the bioactive agents into the skin. The main components of Nanoethosomes are Phospholipids, water, and ethanol. High ethanol concentration in Nanoethosomes distinguishes them from other nano-formulation and results in deeper permeation and smaller vesicular size. This review article gives detailed information on the formulation techniques, and characterization parameters of nanoethosomes along with the research work done by various researchers in the same field. The compiled manuscript gives detailed elaboration about the various drugs used to treat different diseases which when incorporated in nanoethosomes resulted in better permeability and enhanced bioavailability.

Functional Roles of Mesenchymal Stem Cell-derived Exosomes in Ischemic Stroke Treatment.

Stroke is a life-threatening disease and one of the leading causes of death and physical disability worldwide. Currently, no drugs on the market promote neural recovery after stroke insult, and spontaneous remodeling processes are limited to induce recovery in the ischemic regions. Therefore, promoting a cell-based therapy has been needed to elevate the endogenous recovery process. Mesenchymal stem cells (MSCs) have been regarded as candidate cell sources for therapeutic purposes of ischemic stroke, and their therapeutic effects are mediated by exosomes. The microRNA cargo in these extracellular vesicles is mostly responsible for the positive effects. When it comes to the therapeutic viewpoint, MSCsderived exosomes could be a promising therapeutic strategy against ischemic stroke. The aim of this review is to discuss the current knowledge around the potential of MSCs-derived exosomes in the treatment of ischemic stroke.

The Neuroprotective Role of BCG Vaccine in Movement Disorders: A Review.

Bacillus Calmette-Guérin (BCG) is the first developed vaccine to prevent tuberculosis (TB) and is the world's most widely used vaccine. It has a reconcilable defense in opposition to tuberculosis, meningitis, and miliary disease in children but changeable protection against pulmonary TB. Immune activation is responsible for regulating neural development by activating it. The effect of the BCG vaccine on neuronal disorders due to subordinate immune provocation is useful. BCG vaccine can prevent neuronal degeneration in different neurological disorders by provoking auto-reactive T-cells. In the case of TB, CD4+ T-cells effectively protect the immune response by protecting the central defense. Because of the preceding fact, BCG induces protection by creating precise T-cells like CD4+ T-cells and CD8+ T-cells. Hence, vaccination-induced protection generates specific T-cells and CD4+ T-cells, and CD8+ T-cells. The BCG vaccine may have an essential effect on motor disorders and play a crucial role in neuroprotective management. The present review describes how the BCG vaccine might be interrelated with motor disorders and play a key role in such diseases.

Relation between Apolipoprotein E in Alzheimer's Disease and SARS-CoV-2 and their Treatment Strategy: A Review.

COVID-19, which primarily affects the pulmonary system, turned out to be a global pandemic, whereas the effects on other systems are still unknown. SARS-CoV-2, binds to angiotensinconverting enzyme 2 (ACE2) receptors in the lungs, causing pneumonia-like symptoms. The same ACE receptors are also present in organs other than the lungs. Therefore, there is a need to study the impact of coronavirus on other human body organs. Recently, UK Biobank reports on the genetic risk factor of the virus attack. A double mutation in the apolipoprotein E (APOE4) allele has shown a significant role in COVID-19. The same APOE4 mutation has already been proven to hold a key role in developing early-onset Alzheimer's disease (EOAD). Despite this data, Alzheimer's disease is believed to be a comorbidity of COVID-19. Previous virus attacks on the same viral family, Coronaviridae, produced neurological effects like neurodegeneration, neuronal inflammation, and other central nervous system-related dysfunctions. Since the long-term implications of COVID-19 are unknown, more research into the impact of the virus on the central nervous system is needed. Both COVID-19 and AD share a common genetic factor, so that AD patients may have a greater risk of SARS-CoV-2. Here, in this review, we have briefly discussed the role of APOE4 in the pathogenesis of AD and SARS-CoV-2, along with their treatment strategy, current scenario, and possible future directions.

Imbalance of Th1 and Th2 Cytokines and Stem Cell Therapy in Pathological Pain.

The pathophysiological importance of T helper 1 (Th1) and Th2 cell cytokines in pathological pain has been highly debated in recent decades. However, the analgesic strategy targeting individual cytokines still has a long way to go for clinical application. In this review, we focus on the contributions of Th1 cytokines (TNF-α, IFN-γ, and IL-2) and Th2 cytokines (IL-4, IL-5, IL-10, and IL-13) in rodent pain models and human pain-related diseases. A large number of studies have shown that Th1 and Th2 cytokines have opposing effects on pain modulation. The imbalance of Th1 and Th2 cytokines might determine the final effect of pain generation or inhibition. However, increasing evidence indicates that targeting the individual cytokine is not sufficient for the treatment of pathological pain. It is practical to suggest a promising therapeutic strategy against the combined effects of Th1 and Th2 cytokines. We summarize the current advances in stem cell therapy for pain-related diseases. Preclinical and clinical studies show that stem cells inhibit proinflammatory cytokines and release enormous Th2 cytokines that exhibit a strong analgesic effect. Therefore, a shift of the imbalance of Th1 and Th2 cytokines induced by stem cells will provide a novel therapeutic strategy against intractable pain. It is extremely important to reveal the cellular and molecular mechanisms of stem cell-mediated analgesia. The efficiency and safety of stem cell therapy should be carefully evaluated in animal models and patients with pathological pain.

Inhibition of p62-Keap1-Nrf2 Pathway Activation by Realgar Promotes the Inhibition of Esophageal Cancer Cell Proliferation, Migration, and Ferroptosis.

BACKGROUND: Realgar, a Chinese herbal decoction, has been used to treat various types of tumors with positive outcomes; however, there is a lack of convincing evidence on its use for the treatment of esophageal cancer (EC). In this study, the role of the p62-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the regulation of EC cell proliferation, migration, and ferroptosis in response to realgar was assessed. METHODS: Different concentrations of realgar (0, 10, 20, 40, 60, 80, and 100 µmol/L) were applied to the EC cell lines Eca109 and KYSE150. The inhibition rate and half-inhibitory concentration (IC50) were determined using the Cell Counting Kit-8 (CCK-8) method. Subsequently, the cells were treated with realgar (1/2IC50, IC50, 2IC50). Cell migration was measured using the scratch assay, and cell invasion was measured using the transwell assay. The mRNA expression of p62, Keap1, and Nrf2 was measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression of p62, Keap1, Nrf2, matrix metalloproteinase (MMP)-2, MMP-9, E-cadherin, Slug, N-cadherin, and vimentin was measured by Western blot. The control, 2IC50, shRNA-NC, shRNA-p62, 2IC50 + shRNA-NC, 2IC50 + shRNA-p62, shRNA-Keap1, 2IC50 + shRNA-Keap1, and 2IC50 + shRNA-p62 + shRNA-Keap1 groups were defined. The CCK-8 method was used to measure the cell inhibition rate, and the clone formation assay was used to measure the clone formation ability. Moreover, the scratch assay was used to detect the cell migration ability, and the transwell assay was used to detect the cell invasion ability. Transmission electron microscopy was used to observe the mitochondrial morphology, Prussian blue staining was used to observe the intracellular iron particle distribution, and flow cytometry was used to detect changes in intracellular reactive oxygen species. In addition, qRT-PCR was performed to detect p62, Keap1, Nrf2, and glutathione peroxidase 4 (GPX4) mRNA expression, and Western blot was performed to detect p62, Keap1, Nrf2, E-cadherin, Slug, N-cadherin, and GPX4 protein expression. RESULTS: Realgar inhibited Eca109 and KYSE150 cell proliferation in a time- and concentrationdependent manner. It also significantly inhibited the migration and invasion of Eca109 and KYSE150 cells and affected the mRNA and protein expression of p62, Keap1, and Nrf2. In response to realgar, low p62 expression inhibited the proliferation, migration, and invasion of Eca109 and KYSE150 cells, as well as ferroptosis induction. CONCLUSION: The findings demonstrate that inhibiting the p62-Keap1-Nrf2 signaling pathway promotes the inhibitory effects of realgar on EC cells.

Role of Potassium Ion Channels in Epilepsy: Focus on Current Therapeutic Strategies.

BACKGROUND: Epilepsy is one of the prevalent neurological disorders characterized by disrupted synchronization between inhibitory and excitatory neurons. Disturbed membrane potential due to abnormal regulation of neurotransmitters and ion transport across the neural cell membrane significantly contributes to the pathophysiology of epilepsy. Potassium ion channels (KCN) regulate the resting membrane potential and are involved in neuronal excitability. Genetic alterations in the potassium ion channels (KCN) have been reported to result in the enhancement of the release of neurotransmitters, the excitability of neurons, and abnormal rapid firing rate, which lead to epileptic phenotypes, making these ion channels a potential therapeutic target for epilepsy. The aim of this study is to explore the variations reported in different classes of potassium ion channels (KCN) in epilepsy patients, their functional evaluation, and therapeutic strategies to treat epilepsy targeting KCN. METHODOLOGY: A review of all the relevant literature was carried out to compile this article. RESULTS: A large number of variations have been reported in different genes encoding various classes of KCN. These genetic alterations in KCN have been shown to be responsible for disrupted firing properties of neurons. Antiepileptic drugs (AEDs) are the main therapeutic strategy to treat epilepsy. Some patients do not respond favorably to the AEDs treatment, resulting in pharmacoresistant epilepsy. CONCLUSION: Further to address the challenges faced in treating epilepsy, recent approaches like optogenetics, chemogenetics, and genome editing, such as clustered regularly interspaced short palindromic repeats (CRISPR), are emerging as target-specific therapeutic strategies.

The Role of Nutraceutical Supplements in the Treatment of Irritable Bowel Syndrome: A Mini Review.

BACKGROUND: Irritable bowel syndrome (IBS) is a prolonged bowel illness that is generally stress-related and is characterized by a variety of gastrointestinal problems, the most prominent of which is chronic visceral abdominal discomfort. As a result, IBS typically impacts sufferers' standard of living, and it is typically associated with depression and anxiety symptoms. IBS medication is based mostly on symptom alleviation. However, no effective medicines have been discovered too far. As a result, it is essential to discover novel anti-IBS medications. OBJECTIVE: The purpose of this brief review is to describe the existing research on nutraceutical supplements in irritable bowel syndrome management, including probiotics, prebiotics, symbiotics, herbal products, and dietary fibers. METHODS: This review covered the relevant papers from the previous twenty years that were available in different journals such as Science Direct, Elsevier, NCBI, and Web of Science that were related to the role and function of nutraceuticals in Irritable Bowel Syndrome. RESULTS: Nutraceutical substances have a variety of modes of action, including restoring the healthy microbiome, improving the function of the gastrointestinal barrier, immunomodulatory, antiinflammatory, and antinociceptive properties. According to the literature, these substances not only can improve irritable bowel syndrome symptomatology but also have an excellent long-term safety profile. CONCLUSION: Irritable bowel syndrome is a prolonged bowel illness with a lot of gastrointestinal problems. The nutraceuticals treatment works as an anti-IBS intervention and enhances patient compliance with minimum side effects since patients take it better than pharmaceutical treatments.

Liposomal Formulation Improves the Bioactivity of Usnic Acid in RAW 264.7 Macrophage Cells Reducing its Toxicity.

BACKGROUND: Reactive oxygen species (ROS) production and oxidative stress may be responsible for the onset of several chronic diseases. Usnic acid (UA) is a natural secondary metabolite of lichens with several healthful bioactivities, including antioxidant properties. However, UA is a hydrophobic compound known for its hepatic toxicity. These aspects limit its therapeutic applications. To overcome these drawbacks and improve the pharmacological use of hydrophobic compounds, nanotechnology is widely used. Therefore, the incorporation of UA into appropriate nanocarriers could enhance the bioactivity of UA by increasing its solubility. OBJECTIVE: The aim of this work was to improve the solubility of UA and its bioactivity in the absence of cytotoxicity. METHODS: In this study, UA loaded liposomes (UA-LP) were developed. The formulations were chemically and physically characterized, and an in vitro release study was performed. Free UA and UA-LP were tested on RAW 264.7 murine macrophages in terms of cytotoxicity, intracellular ROS production, and NO release in the absence or presence of pro-oxidant LPS stimulus. RESULTS: UA-LP showed excellent physical and chemical stability during storage and improved solubility of UA. UA-LP showed an antioxidant effect in the absence of cytotoxicity compared with free UA on LPS-exposed macrophages. CONCLUSION: For the first time, liposomal formulation improved the beneficial action of UA in terms of solubility and antioxidant activity.

Natural Polymers as a Carrier for the Effective Delivery of Antineoplastic Drugs.

Cancer is a broad term for a set of disorders marked by the development of physically and functionally changed cells that proliferate uncontrollably, infect neighboring tissues, and result in malignant tumours, 'neoplasm'. Cancer remains a difficult disease to treat because of the significant adverse effects and poor pharmacokinetic profile of antineoplastic drugs, despite advancements in our understanding of the features and behavior of tumor cells in recent decades. In this series, the role of natural polymers is prominent as a component of a novel delivery system of anticancer drugs. These natural polymeric drug delivery systems (NPDDS) have many advantages over synthetic polymers like controlled delivery, biodegradability, inexpensive, low toxicity profile, and easily obtainable. These polymers further modify for the targeting of tumour cells. This review discusses and critically analyses the different natural polymers, such as chitosan, cellulose, starch, albumin, dextran, fucoidan, gelatin, etc., in terms of natural ingredient-based polymeric nanocarriers specifically for cancer therapy. It also describes benefits, drawbacks, and opinions and provides insights about the efficacy of NPDDS as well as its future perspectives and tabulated recent patents and cases under clinical trials exploited for cancer treatment.

Age-Related Alterations in Mesenchymal Stem Cell Function: Understanding Mechanisms and Seeking Opportunities to Bypass the Cellular Aging.

Undoubtedly, mesenchymal stem cells (MSCs) are the most common cell therapy candidates in clinical research and therapy. They not only exert considerable therapeutic effects to alleviate inflammation and promote regeneration, but also show low-immunogenicity properties, which ensure their safety following allogeneic transplantation. Thanks to the necessity of providing a sufficient number of MSCs to achieve clinically efficient outcomes, prolonged in vitro cultivation is indisputable. However, either following long-term in vitro expansion or aging in elderly individuals, MSCs face cellular senescence. Senescent MSCs undergo an impairment in their function and therapeutic capacities and secrete degenerative factors which negatively affect young MSCs. To this end, designing novel investigations to further elucidate cellular senescence and to pave the way toward finding new strategies to reverse senescence is highly demanded. In this review, we will concisely discuss current progress on the detailed mechanisms of MSC senescence and various inflicted changes following aging in MSC. We will also shed light on the examined strategies underlying monitoring and reversing senescence in MSCs to bypass the comprised therapeutic efficacy of the senescent MSCs.

Mechanistic Study on the Possible Role of Embelin in Treating Neurodegenerative Disorders.

Embelin (EMB) (2,5-Dihydroxy-3-undecyl-1,4-benzoquinone) is a natural benzoquinone extracted mainly from Embelia ribes (ER) and appear as vivid orange dots beneath the fruit's pericarp. It is being used to treat various diseases since ancient times in India. It has been ascribed as one of the 32 ayurvedic drugs of national importance in the National Medicinal Plant Board set up by the Government of India under the Ministry of Indian System of Medicine and Homeopathy. Embelin prevents neuronal oxidative damage by decreasing the peroxidation of lipids. Along with having antioxidant properties, it also prevents the production of amyloid-protein-related fibrils and blocks the progression of inflammatory cascades. Due to embelin's ability to cross the blood-brain barrier, its neuroprotective effects have been studied in the past using in vitro models of neuronal disorders such as convulsion and epilepsy, Alzheimer's disease, anxiety and depression, traumatic brain injury, cerebral ischemia, Huntington's disease, and multiple sclerosis. In addition to its neuroprotective effects, its role as an antitubercular, anti-cancer, antioxidant, astringent, anti-inflammatory, anti-bacterial, contraceptive, carminative, diuretic, and anthelmintic agent has also been studied. With docking studies and recent advancements in formulations of embelin including polyethylene and embelin micelles and embelin noisome preparations, embelin can prove to be a promising compound for its therapeutic actions in a wide range of diseases and disorders. The findings of docking studies suggest the binding ability of embelin to be similar to the standard drug in their respective disorders. In this review and docking analysis, we bring an outline of scientific evidence concerning the neuroprotective actions of embelin, still, further research is required for its prospective as a chief compound in clinical approaches.

Effectiveness In Vivo and In Vitro of Polymeric Nanoparticles as a Drug Release System in the Treatment of Leishmaniasis.

Leishmaniasis is a neglected disease caused by the parasite of the genus Leishmania. Current treatment regimens are obsolete and cause several side effects, promoting poor patient compliance, in addition to the vast majority already having the potential for resistance. Therefore, polymeric nanoparticles emerge as one of the viable alternatives to overcome existing limitations, through passive or active vectorization. This review aims to summarize the latest studies of polymeric nanoparticles as an alternative treatment for leishmaniasis. In the first section, the main pharmacokinetic and pharmacodynamic challenges of current drugs are reported. The second section details how nanoparticles with and without functionalization are efficient in the treatment of leishmaniasis, discussing the characteristics of the polymer in the formulation. In this way, polymeric nanoparticles can improve the physicochemical properties of leishmanicidal drugs, improving solubility and stability, as well as improve the release of these drugs, directly or indirectly reaching monocytes/macrophages. 64.28% drugs were focused on the treatment of visceral leishmaniasis, and 28.57% on cutaneous leishmaniasis. The most chosen polymers in the literature are chitosan (35.71%) and PLGA (35.71%), the others represented 14.30% drugs, with all able to manage the drug release and increase the in vitro and/or in vivo efficacy of the original molecule. However, there are several barriers for these nanoformulations to cross laboratory research and is necessary more in-depth studies about the metabolites and degradation pathways of the polymers used in the formulations and plasma proteomics studies.