Minor Changes in Response Modules Leading to a "U-Shaped" Conversion Rate of Docetaxel Prodrug Nanoassemblies.

The prodrug-based nanoassemblies offer an alternative to settle the deficiencies of traditional chemotherapy drugs. In this nanosystem, prodrugs typically comprise drug modules, modification modules, and response modules. The response modules are crucial for facilitating the accurate conversion of prodrugs at specific sites. In this work, we opted for differentiated disulfide bonds as response modules to construct docetaxel (DTX) prodrug nanoassemblies. Interestingly, a subtle change in response modules leads to a "U-shaped" conversion rate of DTX-prodrug nanoassemblies. Prodrug nanoassemblies with the least carbon numbers between the disulfide bond and ester bond (PDONα) offered the fastest conversion rate, resulting in powerful treatment outcomes with some unavoidable toxic effects. PDONß, with more carbon numbers, possessed a slow conversion rate and poor antitumor efficacy but good tolerance. With most carbon numbers in PDONγ, it demonstrated a moderate conversion rate and antitumor effect but induced a risk of lethality. Our study explored the function of response modules and highlighted their importance in prodrug development.

Counter-intuitive discovery in the formulation of poorly water-soluble drugs: Amorphous small-molecule gels.

Amorphous strategies have been extensively used in improving the dissolution of insoluble drugs for decades due to their high free energy. However, the formation of amorphous small-molecule gels (ASMGs) presents a counter-intuitive discovery that significantly limits their practical application. Recently, ASMGs have garnered attention because of their noncovalent structures, excellent biodegradability, and significant potential in various drug delivery systems in the pharmaceutical field. Hence, a comprehensive review is necessary to contribute to a better understanding of recent advances in ASMGs. This review aimed to introduce the main formation mechanisms, summarize possible influencing factors, generalize unique properties, outline elimination strategies, and discuss clinical application potential with preclinical cases of ASMGs. Moreover, few ASMGs are advanced to clinical stages. Intensive clinical research is needed for further development. We hope that this review can provide more efficient and rational guidance for exploring further clinical applications of ASMGs.

Rational Engineering Docetaxel Prodrug Nanoassemblies: Response Modules Guiding Efficacy Enhancement and Toxicity Reduction.

Prodrug-based nanoassemblies have been developed to solve the bottlenecks of chemotherapeutic drugs. The fabricated prodrugs usually consist of active drug modules, response modules, and modification modules. Among three modules, the response modules play a vital role in controlling the intelligent drug release at tumor sites. Herein, various locations of disulfide bond linkages were selected as response modules to construct three Docetaxel (DTX) prodrugs. Interestingly, the small structural difference caused by the length of response modules endowed corresponding prodrug nanoassemblies with unique characteristic. α-DTX-OD nanoparticles (NPs) possessed the advantages of high redox-responsiveness due to their shortest linkages. However, they were too sensitive to retain the intact structure in the blood circulation, leading to severe systematic toxicity. ß-DTX-OD NPs significantly improved the pharmacokinetics of DTX but may induce damage to the liver. In comparison, γ-DTX-OD NPs with the longest linkages greatly ameliorated the delivery efficiency of DTX as well as improved DTX's tolerance dose.

Species Difference in the Metabolism of Mulberrin in Vitro and Its Inhibitory Effect on Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes.

This study aimed to evaluate the interspecies difference in metabolism of mulberrin and examine the interaction between mulberrin and CYP enzymes or recombinant human uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes. Liver microsomes from human (HLMs), Beagle dog (DLMs), minipig (PLMs), monkey (MLMs), rabbit (RLMs), rat (RAMs), and mouse (MIMs) were used to investigate metabolic diversity among different species. Additionally, recombinant human supersomes were used to confirm that metabolic enzymes are involved in the biotransformation of mulberrin. We also evaluated the influence of mulberrin on protein expression by Western blot analysis. Mulberrin metabolism showed significant interspecies differences. We found four and two metabolites in phase I and II reaction systems, respectively. In phase I metabolism profiles of mulberrin for HLMs, PLMs and MLMs conformed to the classic Michaelis-Menten kinetics, RAMs and MIMs followed biphasic kinetics; phase II reaction of mulberrin in HLMs, DLMs, PLMs, MLMs, RLMs, RAMs and MIMs followed biphasic kinetics. UGT1A1 were the major CYP isoforms responsible for the metabolism of mulberrin. Mulberrin showed potent inhibitory effects against CYP3A4, CYP2C9, CYP2E1, UGT1A1, UGT1A3 and UGT2B7 with IC50 values of 54.21, 9.93, 39.12, 3.84, 2.01, 16.36 µM, respectively. According to Western blot analysis, mulberrin can upregulate the protein expression of CYP2C19, and downregulate the expression levels of CYP3A5 and CYP2C9 in HepG2 cells as concentration increased. The interspecies comparisons can help find other species with metabolic pathways similar to those in humans for future in vivo studies.

In vitro differences in toddalolactone metabolism in various species and its effect on cytochrome P450 expression.

CONTEXT: Toddalolactone, the main component of Toddalia asiatica (L.) Lam. (Rutaceae), has anticancer, antihypertension, anti-inflammatory, and antifungal activities. OBJECTIVE: This study investigated the metabolic characteristics of toddalolactone. MATERIALS AND METHODS: Toddalolactone metabolic stabilities were investigated by incubating toddalolactone (20 µM) with liver microsomes from humans, rabbits, mice, rats, dogs, minipigs, and monkeys for 0, 30, 60, and 90 min. The CYP isoforms involved in toddalolactone metabolism were characterized based on chemical inhibition studies and screening assays. The effects of toddalolactone (0, 10, and 50 µM) on CYP1A1 and CYP3A5 protein expression were investigated by immunoblotting. After injecting toddalolactone (10 mg/kg), in vivo pharmacokinetic profiles using six Sprague-Dawley rats were investigated by taking 9-time points, including 0, 0.25, 0.5, 0.75, 1, 2, 4, 6 and 8 h. RESULTS: Monkeys showed the greatest metabolic capacity in CYP-mediated and UGT-mediated reaction systems with short half-lives (T1/2) of 245 and 66 min, respectively, while T1/2 of humans in two reaction systems were 673 and 83 min, respectively. CYP1A1 and CYP3A5 were the major CYP isoforms involved in toddalolactone biotransformation. Induction of CYP1A1 protein expression by 50 µM toddalolactone was approximately 50% greater than that of the control (0 µM). Peak plasma concentration (Cmax) for toddalolactone was 0.42 µg/mL, and Tmax occurred at 0.25 h post-dosing. The elimination t1/2 was 1.05 h, and the AUC0-t was 0.46 µg/mL/h. CONCLUSIONS: These findings demonstrated the significant species differences of toddalolactone metabolic profiles, which will promote appropriate species selection in further toddalolactone studies.

Interspecies metabolic diversity of artocarpin in vitro mammalian liver microsomes.

Artocarpin has shown anti-inflammation and anticancer activities. However, the metabolism differences among different species have not been reported. In this work, we used liver microsomes to explore the metabolic characteristics and possible metabolites of artocarpin among different species. The structures of six metabolites were characterized by LC-MS/MS, and hydroxylated artocarpin was the main metabolite. Enzyme kinetics and depletion studies of artocarpin among different species proved that artocarpin metabolism exhibited significant species differences; rats and monkeys showed a great metabolic ability to artocarpin, and minipigs showed the highest similarity to humans. The in vivo hepatic clearances of artocarpin in rats and humans were predicted that artocarpin was classified as a high-clearance drug in humans and rats. The glucuronidation assay of artocarpin in different liver microsomes also proved that artocarpin metabolism showed significant species difference. These findings will support further pharmacological or toxicological research on artocarpin.Abbreviations: UGT: UDP-glucuronosyltransferase; CYP: cytochrome P450; LC-MS/MS: liquid chromatography-tandem mass spectrometry; HPLC: high-performance liquid chromatography; HLMs: human liver microsomes; MLMs: monkey liver microsomes; RAMs: rabbit liver microsomes; RLMs: rat liver microsomes; DLMs: dog liver microsomes; PLMs: minipig liver microsomes; Vmax: maximum velocity; Km: Michaelis constant; CLint: intrinsic clearance; CLH: hepatic clearance; QH: hepatic blood flow.

Quercetin amorphous solid dispersions prepared by hot melt extrusion with enhanced solubility and intestinal absorption.

The aim of this study was to investigate the effect of amorphous solid dispersions (ASDs) on the dissolution rate and oral bioavailability of Quercetin (Que). First, we prepared the Que ASDs with various excipients using hot-melt extrusion to find the best option. X-ray diffraction (XRD), infrared spectroscopy (IR), and Raman spectroscopy were used to examine the solid formation of Que. Wetting process was studied by contact angle and solution process. The abilities of HPMC to inhibit crystallization and improve membrane permeability were demonstrated by fluorescence spectroscopy, dynamic light scattering analysis, in vitro permeability experiment and pharmacokinetics studies. Que existed as amorphous in solid dispersions, and poloxamer 188 (F68) was the best excipient for improving Que dissolution. Study on ASDs wettability proved Que ASDs improved wetting property in the presence of the F68. Furthermore, Que/F68/HPMC 1/4/3 and 1/5/2 ASDs belonged to drug-controlled diffusion; Que/F68/HPMC 1/6/1 ASDs belonged to drug/carrier-controlled diffusion; Que/F68 1/7 ASDs belonged to carrier-controlled diffusion. Addition of HPMC significantly inhibited the crystallization, improved membrane permeability and promoted drug absorption of compound Que. Que ASDs prepared enhanced solubility and intestinal absorption. Thus, Que ASDs provide a potent and efficacious formulation for Que oral administration.

In Vitro Metabolism of Auriculasin and Its Inhibitory Effects on Human Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes.

Auriculasin has a wide range of pharmacological effects, including anticancer and anti-inflammatory effects. In this work, we explored the metabolic characteristics and inhibitory effect of auriculasin against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes in vitro. Auriculasin inhibited UGT1A6, UGT1A8, UGT1A10, UGT2B7, CYP2C9, and CYP3A4 strongly at a concentration of 100 µM. Different species showed significant differences in auriculasin metabolism, and metabolic characteristics were similar between pig and human. We identified seven metabolites, and hydroxylated auriculasin was the main metabolite. In addition, CYP2D6, CYP2C9, CYP2C19, and CYP2C8 were the major CYP isoforms involved in the metabolism of auriculasin. Molecular docking studies showed that noncovalent interactions between auriculasin and the CYPs are dominated by hydrogen bonding, π-π stacking, and hydrophobic interactions. Our in vitro study provides insights into the pharmacological and toxicological mechanisms of auriculasin.

The significant effect of chronic intermittent hypoxia on prostaglandin D2 biosynthesis in rat brain.

Obstructive sleep apnea (OSA) is a common disorder characterized by chronic intermittent hypoxia (CIH). Excessive daytime sleepiness (EDS) is one of severe complications frequently associated with OSA. Lipocalin-type prostaglandin synthase (L-PGDS) is potentially responsible for the production of prostaglandin D2 (PGD2) which is an endogenous sleep inducer. To date, whether the content of PGD2 and PGDS is related to intermittent hypoxia has never been reported. The aim of this study was to compare the content of PGD2 and L-PGDS in rats' brains with and without intermittent hypoxia. Adult male Wistar rats (n = 48; 8-10 weeks) were averagely divided into two groups. One was control group, and the other group was exposed to IH (12 h/day for 6 weeks). In each group there are four time-points including 0, 2, 4 and 6 weeks, and six rats were killed and studied at each time-point. At the end of 0, 2, 4 and 6 weeks, the concentrations of PGD2 in brains were measured by LC-MS/MS. In addition, the expressions of L-PGDS protein and mRNA in brains were investigated by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The results showed the concentrations of PGD2 in CIH rat brains were higher than those in control groups from the second week. At the end of 6 weeks, the concentrations of PGD2 in CIH and control groups were 11.1 and 5.9 ng/g, respectively. The levels of L-PGDS protein and mRNA followed the same trend during the whole 6 weeks. The results will provide a new idea to explore that patients with OSA are always accompanied by excessive daytime sleepiness.

The different metabolism of morusin in various species and its potent inhibition against UDP-glucuronosyltransferase (UGT) and cytochrome p450 (CYP450) enzymes.

1. The aim of this study was to investigate the inhibitory effect of morusin on Glucuronosyltransferase (UGT) isoforms and cytochrome P450 enzymes (CYP450s). We also investigated the metabolism of morusin in human, rat, dog, monkey, and minipig liver microsomes. 2. 100 µM of morusin exhibited strong inhibition on all UGTs and CYP450s. The half inhibition concentration (IC50) values for CYP3A4, CYP1A2, CYP2C9, CYP2E1, UGT1A6, UGT1A7, and UGT1A8 were 2.13, 1.27, 3.18, 9.28, 4.23, 0.98, and 3.00 µM, and the inhibition kinetic parameters (Ki) were 1.34, 1.16, 2.98, 6.23, 4.09, 0.62, and 2.11 µM, respectively. 3. Metabolism of morusin exhibited significant species differences. The quantities of M1 from minipig, monkey, dog, and rat were 7.8, 11.9, 2.0, and 6.3-fold of human levels. The Km values in HLMs, RLMs, MLMs, DLMs, and PLMs were 7.84, 22.77, 14.32, 9.13, and 22.83 µM, and Vmax for these species were 0.09, 1.23, 1.43, 0.15, and 0.75 nmol/min/mg, respectively. CLint (intrinsic clearance) values (Vmax/Km) for morusin obeyed the following order: monkey > rat > minipig > dog > human. CLH (hepatic clearance) values for humans, dogs, and rats were calculated to be 8.28, 17.38, and 35.12 mL/min/kg body weight, respectively. 4. This study provided vital information to understand the inhibitory potential and metabolic behavior of morusin among various species.

Design of berberine hydrochloride sustained-release cold sol using hydroxypropyl methyl cellulose K100M to achieve superior drug dissolution and transdermal absorption.

In this study, berberine hydrochloride (Ber) was used as model drug to prepare a sustained-release cold sol using hydroxypropyl methyl cellulose (HPMC) to achieve superior drug dissolution and transdermal absorption effects. For comparison, a Ber cold sol without HPMC was also prepared using the same method. The preparation process was optimized based on the in vitro release and transdermal permeability of the drug. The results indicated that 1.67 wt% Carbomer 940 and 1.33 wt% HPMC K100M were selected as matrix components with the best sustained-release effect, and drug dissolution of cold sol prepared by combination of these two matrices was significantly slower than the cold sol without HPMC. In addition, transdermal absorption result demonstrated that 0.67 wt% glycerin and 1.33 wt% peppermint oil were the best osmotic enhancers for the optimization of Ber sustained-release cold sol. Herein, HPMC K100M performed important functions in the external application of Ber.

Small molecules modified mesoporous silica nanoparticles orally deliver indomethacin with synergistic effect.

Molecularly functional drug delivery systems possessed huge potentials to realize novel drug administration. To explore small molecules modified drug delivery, a series of small molecules modified mesoporous silica nanoparticles (L-Mal-MSNs, D-Mal-MSNs) were established by grafting small molecules. Poorly water-soluble indomethacin (IMC) was chosen to load into these small molecules modified carriers as well as corresponding control carrier, and further to study characteristics and delivery effects of drug loaded carriers. The results indicated that all these small molecules modified carriers formed hydrogen bonds with drugs and can successfully convert drug crystal phase to amorphous state so as to enhance drug dissolution compared to raw drug. In vivo rat intestinal perfusion demonstrated that IMC loaded L-Mal-MSNs performed the fastest drug absorption while analgesic and anti-inflammatory effects of IMC loaded D-Mal-MSNs turned out to be the best, giving hints that D-malic acid exhibited best synergic functions for IMC. The herein small molecules modified delivery system is an effective solution strategy for the current application of analgesia and anti-inflammatory drugs with outstanding significance.

Cylindrical granules in the development of mesalazine solid formulations (â ¡): The contribution of high aspect ratio to favorable tabletability.

Recently, cylindrical granules have been applied in pharmaceutical fields and their aspect ratio (AR) is considered an important factor in the manufacturing process. However, the relationships between AR and the tableting process were seldom reported. This study aims to clarify the role of AR in the tableting process of cylindrical granules. First, mesalazine cylindrical granules with different AR were extruded, and their physical attributes were then comprehensively characterized. Subsequently, their compression behaviors and tableting performances were systematically assessed. Notably, it was found that the cylindrical granules with high AR possessed good anti-deformation capacity and favorable tabletability. Finally, the dissolution test suggested that tablets compressed from cylindrical granules with higher AR showed lower dissolution rates. Collectively, findings in this study identified that the AR of cylindrical granules was a critical factor in the tableting process and provided valuable guidance for the application of these granules in oral solid formulations.

Associations of global biomarkers of oxidative stress with osteoporosis, bone microstructure and bone turnover: Evidence from human and animal studies.

PURPOSE: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. METHODS: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure. RESULTS: In humans, higher levels of FlOP_320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP_360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP_400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP_320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm3; P = 0.001) than the control group. CONCLUSION: In conclusion, higher FlOP_320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation.

Emerging Chemodynamic Nanotherapeutics for Cancer Treatment.

Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species -mediated cancer therapies, exhibiting its potential as a sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions and hydrogen peroxide to initiate Fenton or Fenton-like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages in cancer treatment are demonstrated, including tumor specificity, autonomy from external triggers, and a favorable side-effect profile. Recent advancements in nanomedicine are devoted to enhancing CDT, promising a comprehensive optimization of CDT efficacy. This review systematically elucidates cutting-edge achievements in chemodynamic nanotherapeutics, exploring strategies for enhanced Fenton or Fenton-like reactions, improved tumor microenvironment modulation, and precise regulation in energy metabolism. Moreover, a detailed analysis of diverse CDT-mediated combination therapies is provided. Finally, the review concludes with a comprehensive discussion of the prospects and intrinsic challenges to the application of chemodynamic nanotherapeutics in the domain of cancer treatment.

Association between amino acids and recent osteoporotic fracture: a matched incident case-control study.

Context: Osteoporotic fracture is a major public health issue globally. Human research on the association between amino acids (AAs) and fracture is still lacking. Objective: To examine the association between AAs and recent osteoporotic fractures. Methods: This age and sex matched incident case-control study identified 44 recent x-ray confirmed fracture cases in the Second Hospital of Jilin University and 88 community-based healthy controls aged 50+ years. Plasma AAs were measured by high performance liquid chromatography coupled with mass spectrometry. After adjusting for covariates (i.e., body mass index, milk intake >1 time/week, falls and physical activity), we conducted conditional logistical regression models to test the association between AAs and fracture. Results: Among cases there were 23 (52.3%) hip fractures and 21 (47.7%) non-hip fractures. Total, essential, and non-essential AAs were significantly lower in cases than in controls. In the multivariable conditional logistic regression models, after adjusting for covariates, each standard deviation increase in the total (odds ratio [OR]: 0.304; 95% confidence interval [CI]: 0.117-0.794), essential (OR: 0.408; 95% CI: 0.181-0.923) and non-essential AAs (OR: 0.290; 95%CI: 0.107-0.782) was negatively associated with recent fracture. These inverse associations were mainly found for hip fracture, rather than non-hip fractures. Among these AAs, lysine, alanine, arginine, glutamine, histidine and piperamide showed the significantly negative associations with fracture. Conclusion: There was a negative relationship between AAs and recent osteoporotic fracture; such relationship appeared to be more obvious for hip fracture.

Supramolecular self-sensitized dual-drug nanoassemblies potentiating chemo-photodynamic therapy for effective cancer treatment.

Chemo-photodynamic synergistic therapy (CPST) holds tremendous promise for treating cancers. Unfortunately, existing CPST applications suffer from complex synthetic procedures, low drug co-loading efficiency, and carrier-related toxicity. To address these issues, we have developed a supramolecular carrier-free self-sensitized nanoassemblies by co-assembling podophyllotoxin (PTOX) and chlorin e6 (Ce6) to enhance CPST efficiency against tumors. The nanoassemblies show stable co-assembly performance in simulative vivo neural environment (∼150 nm), with high co-loading ability for PTOX (72.2 wt%) and Ce6 (27.8 wt%). In vivo, the nanoassemblies demonstrate a remarkable ability to accumulate at tumor sites by leveraging the enhanced permeability and retention (EPR) effect. The disintegration of nanoassemblies following photosensitizer bioactivation triggered by the acidic tumor environment effectively resolves the challenge of aggregation-caused quenching (ACQ) effect. Upon exposure to external light stimulation, the disintegrated nanoassemblies not only illuminate cancer cells synergistically but also exert a more potent antitumor effect when compared with PTOX and Ce6 administered alone. This self-sensitized strategy represents a significant step forward in CPST, offering a unique co-delivery paradigm for clinic cancer treatment.

Cholesterol sulfate-mediated ion-pairing facilitates the self-nanoassembly of hydrophilic cationic mitoxantrone.

HYPOTHESIS: Hydrophilic cationic drugs such as mitoxantrone hydrochloride (MTO) pose a significant delivery challenge to the development of nanodrug systems. Herein, we report the use of a hydrophobic ion-pairing strategy to enhance the nano-assembly of MTO. EXPERIMENTS: We employed biocompatible sodium cholesteryl sulfate (SCS) as a modification module to form stable ion pairs with MTO, which balanced the intermolecular forces and facilitated nano-assembly. PEGylated MTO-SCS nanoassemblies (pMS NAs) were prepared via nanoprecipitation. We systematically evaluated the effect of the ratio of the drug module (MTO) to the modification module (SCS) on the nanoassemblies. FINDINGS: The increased lipophilicity of MTO-SCS ion pair could significantly improve the encapsulation efficiency (∼97 %) and cellular uptake efficiency of MTO. The pMS NAs showed prolonged blood circulation, maintained the same level of tumor antiproliferative activity, and exhibited reduced toxicity compared with the free MTO solution. It is noteworthy that the stability, cellular uptake, cytotoxicity, and in vivo pharmacokinetic behavior of the pMS NAs increased in proportion to the molar ratio of SCS to MTO. This study presents a self-assembly strategy mediated by ion pairing to overcome the challenges commonly associated with the poor assembly ability of hydrophilic cationic drugs.

Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques.

In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy. Numerous antioxidants have been explored for oocyte IVM, yielding considerable effects; however, several aspects, including solubility, stability, and safety, demand attention and resolution. In this study, we developed nanoparticles by self-assembling endogenous bilirubin and melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) to alleviate oxidative stress and enhance oocyte maturation. The optimized MB@GBn exhibited a uniform spherical shape, measuring 128 nm in particle size, with a PDI value of 0.1807 and a surface potential of +11.35 mV. The positively charged potential facilitated nanoparticle adherence to the oocyte surface through electrostatic interaction, allowing for functional action. In vitro studies demonstrated that MB@GB significantly enhanced the maturation of compromised oocytes. Further investigation revealed MB@GB's effectiveness in scavenging ROS, reducing intracellular calcium levels, and suppressing mitochondrial polarization. This study not only offers a novel perspective on nano drug delivery systems for biomedical applications but also presents an innovative strategy for enhancing oocyte IVM.

Curcumin amorphous solid dispersions benefit from hydroxypropyl methylcellulose E50 to perform enhanced anti-inflammatory effects.

The solubility and permeability enhancement of curcumin (Cur) is crucial for its manufacture and application in medical field. Herein, Cur amorphous solid dispersions (ASDs) with enhanced drug solubility and permeability was formulated by Eudragit EPO (EuD) and biological macromolecules of hydroxypropyl methylcellulose E50 (HPMC), and significant functions of HPMC for Cur ASDs were mainly studied. The results showed that the mean particle size of Cur decreased from more than 300 nm to less than 200 nm with the addition of HPMC in excipient aqueous solution evidenced by dynamic light scattering result, confirming that HPMC had the ability to inhibit crystallization by lowering drug-rich droplets in the initial mixing process. Innovatively for molecular dynamic modeling study, crystalline Cur molecules in EuD medium trended to aggregate while not for EuD/HPMC 1:1 and EuD/HPMC 3:1 medium. HPMC functioned as surfactant converted the arrangement of phospholipid bilayers to un-ordered, and un-ordered state of phospholipids lead to the enhancement of Cur transmembrane using HPMC as auxiliary excipient. Cur-EuD/HPMC 3:1 contributed greatly to the Cur permeability, leading to obtain superior relative oral bioavailability and anti-inflammatory effect. Cur ASDs with proper amount of HPMC can be rendered as outstanding therapeutic strategy for medical application.