Preparation and characterization of astaxanthin-loaded liposomes by phytosterol oleate instead of cholesterol.

Hydrophobic bioactive compounds like astaxanthin (AST) exhibit poor water solubility and low bioavailability. Liposomes, which serve as nanocarriers, are known for their excellent biocompatibility and minimal immunogenicity. Traditionally, liposomes have been primarily constructed using phospholipids and cholesterol. However, the intake of cholesterol may pose a risk to human health. Phytosterol ester was reported to reduce level of cholesterol and improve properties of liposomes. In this study, phytosterol oleate was used to prepare liposomes instead of cholesterol to deliver AST (AST-P-Lip). The size range of AST-P-Lip was 100-220 nm, and the morphology was complete and uniform. In vitro studies showed that AST-P-Lip significantly enhanced the antioxidant activity and oral bioavailability of AST. During simulated digestion, AST-P-Lip protected AST from damage by gastric and intestinal digestive fluid. Additionally, AST-P-Lip had a good storage stability and safety. These results provide references for the preparation of novel liposomes and the delivery of bioactive compounds.

Phytoremediation of molybdenum (Mo)-contaminated soil using plant and humic substance.

The severity of soil molybdenum (Mo) pollution is increasing, and effective management of contaminated soil is essential for the sustainable development of soil. To investigate this, a pot experiment was carried out to assess the impact of different rates of humic acid (HA) and fulvic acid (FA) on the mobility of Mo in soil solution and its uptake by alfalfa, wheat and green bristlegrass. The concentration of Mo in Plants and soil was determined using an Atomic Absorption Spectrophotometer. The findings revealed that the application of HA led to an increase in Mo accumulation in the shoot and root of green bristlegrass and wheat, ranging from 10.56 % to 28.73 % and 62.15-115.79 % (shoot), and 17.52-46.53 % and 6.29-81.25 % (root), respectively. Nonetheless, the use of HA resulted in a slight inhibition of plant Mo uptake, leading to reduced Mo accumulation in alfalfa roots compared to the control treatment (from 3284.49 mg/kg to 2140.78-2813.54 mg/kg). On the other hand, the application of FA decreased Mo accumulation in the wheat shoot (from 909.92 mg/kg to 338.54-837.45 mg/kg). Furthermore, the bioavailability of green bristlegrass (with HA) and wheat (with FA) decreased, and the percentage of residual fraction of Mo increased (from 0.39 % to 0.78-0.96 %, from 3.95 % to 3.97∼ 4.34 %). This study aims to elucidate the ternary interaction among Mo, humic substances, and plants (alfalfa, wheat, and green bristlegrass), to enhance both the activation and hyperaccumulation of Mo simultaneously.

Enhanced recovery of waste-born nutrients from sewage sludge ash and fish meal through fungal treatment: Mechanistic insights and impact of heavy metals.

This study investigates the potential of Talaromyces adpressus TCPF to enhance phosphate recovery and nutrient bioavailability from sewage sludge ash (SSA) and fish meal (FM) through co-fermentation. The fungal treatment was found to significantly increase phosphate recovery, achieving up to 16 % efficiency, especially at a 10 g/L waste concentration. The key mechanism behind this enhancement is the production of low molecular weight organic acids (LMWOAs), which played a crucial role in solubilizing nutrients while also mitigating the negative effects of heavy metals like lead and cadmium. Spectroscopic analyses confirmed substantial acid-based leaching and biomineralization processes, with over 70 % of phosphorus successfully bioleached from metal-treated waste. These findings underscore the effectiveness of fungal treatments in transforming waste substrates into valuable bio-organic fertilizers. Fungal treatment boosts phosphate recovery, even in the presence of heavy metals, by employing processes such as bioweathering, bioprecipitation, biocorrosion, and bioleaching.

Dominant role of soil iron and organic matters in arsenic transfer from soil to plant in a mine area in Hunan Province, Central China.

The transfer of arsenic (As) from soil to plant could be significantly influenced by soil parameters through regulating soil As bioavailability. To distinguish the bioavailable As provided by soil and the As uptaken by plants, herein two different soil bioavailable were defined, namely potential soil bioavailable As (evaluated through the bioavailable fraction of As) and actual soil bioavailable As (assessed through plant bioaccumulation factor, BF, and BFavailable). To identify the dominant soil parameters for the two soil bioavailable As forms, soil and plant samples were collected from a former As mine site. The results showed that the potential bioavailable As only accounted for 1.77 to 11.43% in the sampled soils, while the BF and BFavailable in the sampled vegetables ranged from 0.00 to 1.01 and 0.01 to 17.87, respectively. Despite a similar proportion of As in the residual fraction, soil with higher pH and organic matter (OM) content and lower iron (Fe) content showed a higher potential soil bioavailable As. Correlation analysis indicated a relationship between the soil pH and potential soil bioavailable As (r = 0.543, p < 0.01) and between the soil Fe and actual soil bioavailable As (r = - 0.644, p < 0.05, r = - 0.594, p < 0.05). Stepwise multiple linear regression (SMLR) analysis was employed to identify the dominant soil parameters and showed that soil pH and phosphorus (P) content could be used to predict the potential soil bioavailable As (R2 = 0.69, p < 0.001). On the other hand, soil Fe and OM could be used to predict the actual soil bioavailable As (R2 = 0.18-0.86, p < 0.001-0.015, in different vegetables). These results suggest that different soil parameters affect potential and actual soil bioavailable As. Hence, soil Fe and OM are the most important parameters controlling As transfer from soil to plant in the investigated area.

Mind the Particle Rigidity: Blooms the Bioavailability via Rapidly Crossing the Mucus Layer and Alters the Intracellular Fate of Curcumin.

Overcoming intestinal epithelial barriers to enhance bioavailability is a major challenge for oral delivery systems. Desirable nanocarriers should simultaneously exhibit rapid mucus penetration and efficient epithelial uptake; however, they two generally require contradictory structural properties. Herein, we proposed a strategy to construct multiperformance nanoparticles by modifying the rigidity of amphiphilic nanostructures originating from soy polypeptides (SPNPs), where its ability to overcome multibarriers was examined from both in vitro and in vivo, using curcumin (CUR) as a model cargo. Low-rigidity SPNPs showed higher affinity to mucin and were prone to getting stuck in the mucus layer. When they reached epithelial cells, they tended to be endocytosed through the clathrin and macropinocytosis pathways and further transferred to lysosomes, showing severe degradation and lower transport of CUR. Increased particle rigidity generally improved the absorption of CUR, with medium-rigidity SPNPs bloomed maximum plasma concentration of CUR by 80.62-fold and showed the highest oral bioavailability. Results from monocultured and cocultured cell models demonstrated that medium-rigidity SPNPs were least influenced by the mucus layer and changes in rigidity significantly influenced the endocytosis and intracellular fate of SPNPs. Those with higher rigidity preferred to be endocytosed via a caveolae-mediated pathway and trafficked to the ER and Golgi, facilitating their whole transcytosis, and avoiding intracellular metabolism. Moreover, rigidity modulation efficiently induces the reversible opening of intercellular tight junctions, which synergistically improves the transport of CUR into blood circulation. This study suggested that rigidity regulation on food originated amphiphilic peptides could overcome multiple physiological barriers, showing great potential as natural building block toward oral delivery.

Seasonal dynamics of amino acids in the Southern Yellow Sea: Feedback on the mechanism of green tides caused by Ulva prolifera.

The biogeochemical processes of amino acids in the Southern Yellow Sea (SYS) have become more dynamic under the influence of the world's largest-scale green tide. The potential relationship between amino acids and green tides has not been effectively assessed, despite its critical importance for exploring dissolved organic matter (DOM) cycling processes in marginal seas. In this study, three cruises were conducted to analyze the concentrations and compositions of total hydrolyzed amino acids (THAAs) in the SYS during the spring, summer, and autumn of 2019. The bioavailability potential of DOM was evaluated using the degradation index (DI) and THAA nitrogen normalized yield (THAA (%DON)) (DON as dissolved organic nitrogen). The variation dynamics of amino acid indicators during different stages of green tide were further explored. The results showed that the THAA concentrations and DOM bioavailability in the SYS were considerably influenced by biological processes. The THAA concentrations (0.96 ± 0.34 µmol L-1) exhibited the lowest mean values in the summer, while the DI values (0.106 ± 0.461) and mean THAA (%DON) values (18.20 ± 6.58 %) were the highest during this season. The distribution of amino acid indicators in the summer (the late-tide stage) was regulated by the green tide mechanism, and kept pace with the green tide floating region. In comparison with the waters in south of 35° N, the THAA concentrations and DI values experienced significant seasonal variations (p < 0.05) in north of 35° N, with the highest DI values (1.217) observed in the green tide aggregation area. This indicates the transformation of nutrient sources for Ulva prolifera in the late-tide stage and its impact on DOM bioavailability. Thus, as a potential feedback indicator of green tides, the study of amino acids is meaningful for understanding the occurrence of green tides and the source-sink pattern of organic nitrogen.

Studies on absorption mechanism and pharmacokinetic properties of albendazole-bile acid conjugate: In vivo and in vitro.

PURPOSE: To improve the oral bioavailability of albendazole (ABZ), a series of albendazole-bile acid conjugates (ABCs) were synthesized. ABC's transmembrane transport mechanism and in vivo pharmacokinetic properties were preliminarily studied. METHODS: The transmembrane transport mechanism of ABCs was studied using the Caco-2 monolayer cell model and intestinal perfusion model. The concentration of ABCs and ABZ were evaluated using High-Performance Liquid Chromatography (HPLC) and HPLC-Mass Spectrometry (HPLC-MS/MS). RESULTS: Compared to ABZ, better permeability was observed for different types and concentrations of ABCs using the Caco-2 monolayer cell model, with ABC-C8 showing the highest permeability. The transmembrane transport of ABCs was affected by ASBT inhibitors, indicating an ASBT-mediated active transport mechanism. Additionally, introducing cholic acid resulted in ABZ no longer being a substrate for P-gp, MRP2, and BCRP, effectively reversing ABZ efflux. In vivo unidirectional intestinal perfusion results in rats showed that ABCs altered the absorption site of ABZ from the jejunum to the ileum. The absorption efficiency of ABCs in each intestinal segment was higher than that of ABZ, and the transmembrane transport efficiency decreased with increasing concentrations of ASBT inhibitors. This further confirmed the presence of both passive diffusion and ASBT-mediated active transport mechanisms in the transport of ABCs. The solubility of ABCs in gastric juice and pharmacokinetics in rats showed that ABZ-C4 exhibited enhanced solubility. Moreover, ABCs significantly increased oral bioavailability compared to ABZ, with ABC-C4 showing an approximately 31-fold increase in bioavailability. CONCLUSION: The transmembrane transport mechanism of ABCs involves a combination of ASBT-mediated active transport and passive diffusion. Moreover, the incorporation of BAs successfully reverses the efflux of ABZ by efflux proteins. Among the synthesized conjugates, ABC-C4 demonstrated superior dissolution behavior both in vitro and in vivo.

Assessing soil remediation effect of Cr and Pb based on bioavailability using DGT, BCR and standardized determination method.

In the field of soil remediation, the importance of bioavailability of pollutants has not received adequate attention, leading to the excessive application of remediation measures. Therefore, to ensure the safe use of farmland soil, a scientific method is needed to assess labile contaminants and their translocation in plants. To evaluate soil remediation effect based on bioavailability, the concentrations of these heavy metals in soil were analyzed using by the method for total metal content, the Community Bureau of Reference (BCR) extraction, and the diffusive gradients in thin films (DGT) technique. The results reveal that the correlation coefficients between metal concentrations measured by DGT and those accumulated in rice grains are the highest (Cr-R2 = 0.8966, Pb-R2 = 0.9045). However, the capability of method for total metal content to evaluate the remediation effect of heavy metals is very limited. In contrast, although Cr and Pb measured by BCR show a high correlation with HMs in rice plants, the method still falls short in precisely assessing bioavailability. Significantly, DGT proves to be more effective, successfully distinguishing the remediation effects of different treatments. Generally, DGT offers a more accurate and simpler assessment method, underscoring its practical significance for monitoring soil remediation and environmental management.

Intranasal delivery of sulpiride nanostructured lipid carrier to central nervous system; in vitro characterization and in vivo study.

The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol®888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL in vitro release, nanodispersion stability, in vivo performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly (p < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders.

Investigation of the dissolution rate and oral bioavailability of atenolol-irbesartan co-amorphous systems.

Irbesartan (IBS), a common drug to treat hypertension, has poor oral bioavailability because of its limited aqueous solubility. Recently, co-amorphous systems (CAMs) have demonstrated the ability to improve the solubility of poorly water-soluble drugs. In this study, IBS was co-amorphized with a pharmacologically relevant drug atenolol (ATL) by melt-quenching. The structures of the resulting ATL-IBS CAMs, which were formulated in molar ratios of 2:1, 1:1, 1:2 and 1:4, were characterized by the polarizing microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier-infrared transform spectroscopy. ATL-IBS CAM1:1 showed higher IBS dissolution than crystalline IBS, amorphous IBS (IBS AM) and the other CAMs. The results of the supersaturated solution stability showed that ATL enhanced the supersaturation maintenance of IBS by extensive interactions. The CAMs exhibited excellent physical stability at 25 °C/60 % RH. The pharmacokinetics experiments showed that the relative oral bioavailability of IBS was 2.78-fold higher than bulk IBS (p < 0.001) after oral administration of ATL-IBS CAM1:1 to rats. The results of this study demonstrate that CAMs provide an alternative option for the development of fixed dose combination of ATL and IBS.

Pharmaceutical approaches for enhancing solubility and oral bioavailability of poorly soluble drugs.

High solubility in water and physiological fluids is an indispensable requirement for the pharmacological efficacy of an active pharmaceutical ingredient. Indeed, it is well established that pharmaceutical substances exhibiting limited solubility in water are inclined towards diminished and inconsistent absorption following oral administration, consequently resulting in variability in therapeutic outcomes. The current advancements in combinatorial chemistry and pharmaceutical design have facilitated the creation of drug candidates characterized by increased lipophilicity, elevated molecular size, and reduced aqueous solubility. Undoubtedly, the issue of poorly water-soluble medications has been progressively escalating over recent years. Indeed, 40% of the top 200 oral medications marketed in the United States, 33% of drugs listed in the US pharmacopoeia, 75% of compounds under development and 90% of new chemical entities are insufficiently water-soluble compounds. In order to address this obstacle, formulation scientists employ a variety of approaches, encompassing both physical and chemical methods such as prodrug synthesis, salt formation, solid dispersions formation, hydrotropic substances utilization, solubilizing agents incorporation, cosolvent addition, polymorphism exploration, cocrystal creation, cyclodextrins complexation, lipid formulations, particle size reduction and nanoformulation techniques. Despite the utilization of these diverse approaches, the primary reason for the failure in new drug development persists as the poor aqueous solubility of pharmaceutical compounds. This paper, therefore, delves into the foundational principles that underpin the implementation of various formulation strategies, along with a discussion on the respective advantages and drawbacks associated with each approach. Additionally, a discourse is provided regarding methodological frameworks for making informed decisions on selecting an appropriate formulation strategy to effectively tackle the key challenges posed during the development of a poorly water-soluble drug candidate.

ICH M10 Bioanalytical Method Validation Guideline-1 year Later.

The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) adopted Guideline M10 entitled "Bioanalytical Method Validation and Study Sample Analysis" in May 2022. In October 2023, approximately one year after the adoption of the ICH M10 guideline, a "Hot Topic" session was held during the AAPS PharmSci 360 meeting to discuss the implementation of the guideline. The session focused on items the bioanalytical community felt were challenging to implement or ambiguous within the guideline. These topics included cross-validation, parallelism, comparative bioavailability studies, combination drug stability, endogenous analyte bioanalysis, and dilution QCs. In addition, the regulatory perspective on the guideline was presented. This report provides a summary of the Hot Topic session.

Comprehensive review of Hesperetin: Advancements in pharmacokinetics, pharmacological effects, and novel formulations.

Hesperetin is a flavonoid compound naturally occurring in the peel of Citrus fruits from the Rutaceae family. Previous studies have demonstrated that hesperetin exhibits various pharmacological effects, such as anti-inflammatory, anti-tumor, antioxidative, anti-aging, and neuroprotective properties. In recent years, with the increasing prevalence of diseases and the rising awareness of traditional Chinese medicine, hesperetin has garnered growing attention for its wide-ranging pharmacological effects. To substantiate its health benefits and elucidate potential mechanisms, knowledge of pharmacokinetics is crucial. However, the limited solubility of hesperetin restricts its bioavailability, thereby diminishing its efficacy as a beneficial health agent. To enhance the bioavailability of hesperetin, various novel formulations have been developed, including nanoparticles, liposomes, and cyclodextrin inclusion complexes. This article reviews recent advances in the pharmacokinetics of hesperetin and methods to improve its bioavailability, as well as its pharmacological effects and mechanisms, aiming to provide a theoretical basis for clinical applications.

Disposition kinetics and bioavailability of doxycycline after parenteral administrations in ewes.

Doxycycline is a tetracycline, which have been marketed in different species for treating infections caused by susceptible bacteria. There is limited information on the disposition kinetics of this drug in ewes and this antimicrobial may be useful against several sheep pathogens that are common causes of morbidity and economic loss. Therefore, the aim of this work was to establish the pharmacokinetics of doxycycline after intravenous (IV) and extravascular (subcutaneous (SC) and intramuscular (IM)) administrations in this species. A cross-over model was designed (n = 6). Doxycycline was dosed at 5 mg/kg for IV administration and 20 mg/kg for extravascular administrations. Non-compartmental pharmacokinetic methods were used to calculate plasma concentration-time data. The value of apparent volume of distribution (Vz) suggests a moderate distribution of this antibiotic in sheep, with a value of 0.84 L/kg. The maximum concentrations achieved after extravascular administrations (Cmax) were similar, with no significant differences between the two routes of administration (IM and SC). However, doxycycline absorption was slower after SC administration than after IM administration, taking twice as long to reach maximum plasma concentration (tmax). Bioavailabilities after extravascular routes of administration were low and after IM administration doxycycline caused lameness in all animals. Therefore, the SC administration showed a better profile with respect to pharmacokinetic properties and safety. Future studies on the susceptibility of isolated sheep pathogens to doxycycline are needed to establish appropriate dosing regimens.

Evaluation of the bioavailability of a Tamiflu taste-masking pediatric formulation using a juvenile pig model and LC-MS/MS.

Aim: To improve the palatability and increase compliance in pediatric patients, different taste-masking technologies have been evaluated to support the NIH Pediatric Formulation Initiative.Methods: This bioavailability approach combined a juvenile porcine model which represented the pediatric population, and an advanced UHPLCMS/MS method. Juvenile pigs were administered with either commercial Tamiflu or its taste-masking formulation and plasma samples were obtained from 0 to 48 h. The mass spectrometer was operated in positive mode with electrospray ionization.Results: The bioavailability profiles were not significantly different between the two formulations which demonstrated that taste-masking by forming an ionic complex was a promising approach for formulation modification.Conclusion: The pre-clinical study revealed a promising model platform for developing and screening taste-masking formulations.

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Pharmacokinetics and Bioequivalence of a Generic Ticagrelor 90-mg Formulation Versus the Innovator Product in Healthy White Subjects Under Fasting Conditions.

Ticagrelor is a key antiplatelet agent used to prevent thrombotic events in patients with acute coronary syndrome. This open-label, 2-period, crossover Phase I study assessed the pharmacokinetics and bioequivalence of a generic ticagrelor 90-mg formulation compared to the innovator product under fasting conditions. Twenty-eight healthy White adults participated in the study. Each participant received a single dose of either the test or reference formulation, followed by a 7-day washout period before switching to the alternate formulation. Plasma concentrations of ticagrelor were measured using a validated high-performance liquid chromatography-tandem mass spectrometry method. Statistical analysis of primary pharmacokinetic parameters, including maximum concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, showed bioequivalence with test/reference ratios of 110.9% and 107.1%, respectively, and 90% confidence intervals within the 80%-125% regulatory range. Treatment-emergent adverse events, such as headache, dysphagia, and dizziness, were moderate and transient and resolved promptly, with no significant difference in incidence between the formulations. These results confirm that the generic ticagrelor formulation is bioequivalent to the innovator product, supporting its use as an interchangeable option in clinical practice.

Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications.

This study aims to enhance the solubility of Olaparib, classified as biopharmaceutical classification system (BCS) class IV due to its low solubility and bioavailability using a solid self-nanoemulsifying drug delivery system (S-SNEDDS). For this purpose, SNEDDS formulations were created using Capmul MCM as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. The SNEDDS formulation containing olaparib (OLS-352), selected as the optimal formulation, showed a mean droplet size of 87.0 ± 0.4 nm and drug content of 5.53 ± 0.09%. OLS-352 also demonstrated anticancer activity against commonly studied ovarian (SK-OV-3) and breast (MCF-7) cancer cell lines. Aerosil® 200 and polyvinylpyrrolidone (PVP) K30 were selected as solid carriers, and S-SNEDDS formulations were prepared using the spray drying method. The drug concentration in S-SNEDDS showed no significant changes (98.4 ± 0.30%, 25℃) with temperature fluctuations during the 4-week period, demonstrating improved storage stability compared to liquid SNEDDS (L-SNEDDS). Dissolution tests under simulated gastric and intestinal conditions revealed enhanced drug release profiles compared to those of the raw drug. Additionally, the S-SNEDDS formulation showed a fourfold greater absorption in the Caco-2 assay than the raw drug, suggesting that S-SNEDDS could improve the oral bioavailability of poorly soluble drugs like olaparib, thus enhancing therapeutic outcomes. Furthermore, this study holds significance in crafting a potent and cost-effective pharmaceutical formulation tailored for the oral delivery of poorly soluble drugs.

Nanocarrier-Based Delivery Approaches of Mangiferin: An Updated Review on Leveraging Biopharmaceutical Characteristics of the Bioactive.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.