Asymmetric Photoinduced Excited-State Nazarov Reaction.

We report herein the first asymmetric photoinduced excited-state Nazarov reaction of non-aromatic dicyclic divinyl ketones by using hydrogen-bonding catalysis. The enantioselectivity of photoinduced electrocyclization is highly dependent on the structural features of the substrate and its interaction with chiral catalysts. For the simple dicyclic divinyl ketone substrates, there is no discernible selectivity of the hydrogen bond coordination between the thiourea and carbonyl groups of the substrates in the ground state. However, we found that the direction of the electrocyclization was well controlled in each coordination model and the N,N'-dimethylamine motif acts as a base in the regioselective deprotonation process, which leads to the formation of two stereoisomers with high enantioselectivity. Photolysis of dicyclic divinyl ketones bearing a 1,3-dioxolane motif in the presence of bifunctional hybrid peptide-thiourea chiral catalysts gave the tricyclic cis-hydrofluorenones with good enantioselectivity. Mechanistic and DFT studies suggested that the amide and thiourea groups in the bifunctional chiral catalysts play a key role as H-bond donors, which coordinate with both the carbonyl group and the 1,3-dioxolane motif to provide a more favorable chiral species, and control the direction of the electrocyclization. Due to the presence of the rigid 1,3-dioxolane ring, the deprotonation/protonation process occurs regiospecifically with high driving force. This photo-electrocyclization is mild (room temperature and neutral solution), which results a broad reaction scope and functional group tolerance and demonstrates its synthetic potential in organic synthesis.

Synthesis of the DEF-Ring Spirocyclic Core of Cyclopamine.

A stereoselective synthesis of the DEF-ring spirocyclic core of cyclopamine was accomplished using commercially available materials. The key steps in the synthesis were (i) the enantioselective vinylogous Mannich reaction, followed by lactamization to generate the piperidine F ring, and (ii) intramolecular oxidative dearomative spiroetherification to construct the DEF-ring spirocyclic core of cyclopamine. We found that the stereochemistry of the spirocyclization was controlled by the configuration of the methyl group (C-20) in the substrate.

Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

Moderate alternate wetting and drying irrigation enhances drought-resistance abilities by improving structural mesophyll conductance of water-saving and drought-resistant rice under severe drought.

Water-saving and drought-resistant rice (WDR) coupled with alternate wetting and drying irrigation (AWDI) possesses a high photosynthetic potential due to higher mesophyll conductance (gm) under drought conditions. However, the physiological and structural contributions to the gm of leaves and their mechanisms in WDR under AWDI are still unclear. In this study, WDR (Hanyou 73) and drought-sensitive rice (Huiliangyou 898) were selected as materials. Three irrigation patterns were established from transplanting to the heading stage, including conventional flooding irrigation (W1), moderate AWDI (W2), and severe AWDI (W3). A severe drought with a soil water potential of -50 kPa was applied for a week at the heading stage across all treatments and cultivars. The results revealed that severe drought reduced gas exchange parameters and gm but enhanced antioxidant enzyme activities and malondialdehyde content in the three treatments and both cultivars. The maximal photosynthetic rate (Amax) of HY73 in the W2 treatment was greater than that in the other combinations of cultivars and irrigation patterns. The contribution of leaf structure (54%) to gm (gm-S, structural gm) was higher than that of leaf physiology (46%) to gm (gm-P, physiological gm) in the W2 treatment of Hanyou 73. Additionally, gm-S was significantly and linearly positively correlated with gm under severe drought. Moreover, both the initial and apparent quantum efficiencies were significantly and positively with gm in rice plants (p < 0.05). These results suggest that the improvements in photosynthesis and yield in the WDR combined with moderate AWDI can mainly be attributed to the enhancement of gm-S under severe drought conditions. Quantum efficiency may be a potential factor in regulating photosynthesis by cooperating with the gm of rice plants under severe drought conditions.

Construction and in vitro/in vivo evaluation of menantine hydrochloride oral liquid sustained-release drug delivery system.

OBJECTIVE: The purpose of the present study was to formulate a menantine hydrochloride (MH) sustained-release suspension. METHODS: Menantine hydrochloride drug resin complex (MH-DRC) was prepared with strong acid cation exchange resin as carrier using water bath method. The MH-DRC was characterized using scanning electron microscopy, X-ray diffraction and infrared spectroscopy. The MH-coated microcapsule (MH-CM) with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. The rats were given both the MH sustained-release suspension and the commercial MH sustained-release capsule by intragastric administration. The plasma concentration-time curves and related pharmacokinetic parameters were also investigated using a non-atrioventricular model. RESULTS: MH and ion-exchange resin were ionically bonded. AmberliteIRP®69 had a higher affinity for MH at the initial concentration of 5 mg·mL-1 and a reaction temperature of 25.0 ± 0.5 °C. In vitro drug release profile showed that both the drug resin complex and the coated microcapsules had a certain level of sustained-release effect. The t1/2 of MH sustained-release suspension was extended from 68.44 h to 72.79 h with the peak blood concentration being decreased to 3.56 µg·mL-1 and the Tmax extended to 12 h compared with the commercial MH sustained-release capsule. The concentration-time curve of the self-made MH sustained-release suspension was flattened and the average relative bioavailability (Fr) was 116.65% compared with the commercial MH sustained-release capsules. CONCLUSIONS: The findings showed that the MH sustained-release suspension was successfully formulated with acceptable pharmacokinetic indices for effective treatment of Alzheimer's disease.

Preparation and in vitro/in vivo evaluation of a pantoprazole sodium drug-resin liquid delayed release suspension.

A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer treatment in children, the elderly and patients with dysphagia. Pantoprazole sodium drug-resin complexes (PAZ-Na-DRC) were prepared using the bath method. The fluidized bed coating method is used to coat it and then add excipients to make a dry suspension prepared before use. The parameters of the in vitro release experimental conditions were optimized and the drug release curve showed delayed release. Rats were given commercial PAZ-Na enteric-coated pellet capsules and the PAZ-Na delayed release suspension via intragastric administration. The results showed that the Tmax of the PAZ-Na delayed release suspension was increased from 2h to 4h compared with the PAZ-Na enteric-coated pellet capsules. Similarly, the Cmax was reduced from 6.162µg/mL to 3.244µg/mL with the concentration-time curve is very gentle compared with the commercial drug capsules. After oral administration, the relative bioavailability of PAZ-Na delayed release suspension (AUC0-24 of 19.578 µg•h•mL-1) compared with the commercial drug (AUC0-24 of 17.388 µg•h•mL-1) was 112.67%. The findings showed that the PAZ-Na delayed release suspension for oral administration was successfully formulated with highly improved pharmacokinetic indices.

Development and in vitro/in vivo evaluation of famotidine hydrochloride bioadhesive sustained release suspension.

To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension. Pharmacokinetics of the developed microcapsules were studied in the gastrointestinal tract of rats. The self-made sustained-release suspension of famotidine hydrochloride effectively reduced the blood concentration and prolonged the action time. The relative bioavailability of the self-made suspension of the famotidine hydrochloride to the commercially available famotidine hydrochloride was 146.44%, with an average retention time of about 5h longer, which indicated that the new suspension had acceptable adhesion properties. The findings showed that the newly developed famotidine-resin microcapsule increased the bioavailability of the drug with a significant sustained-release property.

Asymmetric Total Synthesis of Cephalotaxus Diterpenoids: Cephinoid P, Cephafortoid A, 14-epi-Cephafortoid A and Fortalpinoids M-N, P.

The asymmetric total syntheses of cephalotaxus C19 diterpenoids, bearing a unique cycloheptene A ring with a chiral methyl group at C-12, were disclosed based on a universal strategy. Six members, including cephinoid P, cephafortoid A, 14-epi-cephafortoid A and fortalpinoids M-N, P, were accomplished for the first time. The concise approach relies on two crucial steps: (1) a Nicholas/Hosomi-Sakurai cascade reaction was developed to efficiently generate the cycloheptene ring bearing a chiral methyl group; (2) an intramolecular Pauson-Khand reaction was followed to facilitate the construction of the complete skeleton of target molecules. Our studies provide a new strategy for the synthetic analysis of cephalotaxus diterpenoids and structurally related polycyclic natural products.

Asymmetric Synthesis of Cyclopamine, a Hedgehog (Hh) Signaling Pathway Inhibitor.

Cyclopamine is a teratogenic steroidal alkaloid, which inhibits the Hedgehog (Hh) signaling pathway by targeting the Smoothened (Smo) receptor. Suppression of Hh signaling with synthetic small molecules has been pursued as a therapeutic approach for the treatment of cancer. We report herein the asymmetric synthesis of cyclopamine based on a two-stage relay strategy. Stage-I: total synthesis of veratramine through a convergent approach, wherein a crucial photoinduced excited-state Nazarov reaction was applied to construct the basic [6-6-5-6] skeleton of C-nor-D-homo-steroid. Stage-II: conversion of veratramine to cyclopamine was achieved through a sequence of chemo-selective redox manipulations.

Human Serum Albumin Nanoparticles as a Carrier of 20(S)-Protopanaxadiol via Intramuscular Injection to Alleviate Cyclophosphamide-Induced Myelosuppression.

Myelosuppression is a prevalent and potentially life-threatening side effect during chemotherapy. As the main active component of ginseng, 20(S)-protopanaxadiol (PPD) is capable of relieving myelosuppression by restoring hematopoiesis and immunity. In this study, PPD was encapsulated in human albumin nanoparticles (PPD-HSA NPs) by nanoparticle albumin-bound (Nab) technology for intramuscular injection to optimize its pharmacokinetic properties and promote recovery of myelosuppression. The prepared PPD-HSA NPs had a particle size of about 280 nm with a narrow size distribution. PPD dispersed as an amorphous state within the PPD-HSA NPs, and the NPs exhibited in vitro sustained release behavior. PPD-HSA NPs showed a favorable pharmacokinetic profile with high absolute bioavailability, probably due to the fact that NPs entered into the blood circulation via lymphatic circulation and were eliminated slowly. In vivo distribution experiments demonstrated that PPD-HSA NPs were mainly distributed in the liver and spleen, but a strong fluorescence signal was also found in the inguinal lymph node, indicating drug absorption via a lymph route. The myelosuppressive model was established using cyclophosphamide as the inducer. Pharmacodynamic studies confirmed that PPD-HSA NPs were effective in promoting the level of white blood cells. Moreover, the neutrophil and lymphocyte counts were significantly higher in the PPD-HSA NPs group compared with the control group. This preliminary investigation revealed that PPD-HSA NPs via intramuscular administration may be an effective intervention strategy to alleviate myelosuppression.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of perfluorinated compounds.

Perfluorinated compounds (PFCs) are man-made chemicals used in the manufacture of many products with water and dirt repellent properties. Many diseases have been proved to be related to the exposure of PFCs, including breast fibroadenoma, hepatocellular carcinoma, breast cancer and leydig cell adenoma. However, whether the PFCs promote the progression of prostate cancer remains unclear. In this work, through comprehensive bioinformatics analysis, we discovered the correlation between the prostate cancer and five PFCs using Comparative Toxicogenomics Database (CTD), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, further analysis showed that several PFCs-related genes demonstrated strong prognostic value for prostate cancer patients. The survival analysis and receiver operating characteristic (ROC) curves revealed that PFCs-related genes based prognostic model held great predictive value for the prognosis of prostate cancer, which could potentially serve as an independent risk factor in the future. In vitro experiments verified the promotive role of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) in the growth of prostate cancer cells. This study provided novel insights into understanding the role of PFCs in prostate cancer and brought attention to the environmental association with cancer risks and progression.

Antibacterial-Anti-Inflammatory-Bone Restoration Procedure Achieved by MIN-Loaded PLGA Microsphere for Efficient Treatment of Periodontitis.

The main development process of periodontitis involves periodontal pathogenic bacteria as the initiating factor causing the onset of destructive inflammation, which in turn stimulates the destruction of periodontal tissue. It is difficult to achieve the eradication of periodontitis due to the complex interaction among antibacterial, anti-inflammatory, and bone restoration. Herein, we propose an antibacterial-anti-inflammatory-bone restoration procedural treatment strategy with minocycline (MIN) for the efficient treatment of periodontitis. In brief, MIN was prepared into PLGA microspheres with tunable release behavior using different species of PLGA, respectively. The optimally selected PLGA microspheres (LA:GA with 50:50, 10 kDa, and carboxyl group) had a drug loading of 16.91%, an in vitro release of approximately 30 days, which also had a particle size of approximately 11.8 µm with a smooth appearance and a rounded morphology. The DSC and XRD results showed that the MIN was completely encapsulated in the microspheres as an amorphous state. Cytotoxicity tests demonstrated the safety and biocompatibility of the microspheres (cell viabilities at a concentration of 1-200 µg/mL were greater than 97%), and in vitro bacterial inhibition tests showed that the selected microspheres could achieve effective bacterial inhibition at the initial stage after administration. The favorable anti-inflammatory (low TNF-α and IL-10 levels) and bone restoration effects (BV/TV: 71.8869%; BMD: 0.9782 g/cm3; TB.Th: 0.1366 mm; Tb.N: 6.9318 mm-1; Tb.Sp: 0.0735 mm) were achieved in a SD rat periodontitis model after administering once a week for four weeks. The MIN-loaded PLGA microspheres were proved to be an efficient and safe treatment for periodontitis by procedural antibacterial, anti-inflammatory, and bone restoration.

Asymmetric Total Synthesis of Hasubanan Alkaloids: Periglaucines A-C, N,O-Dimethyloxostephine and Oxostephabenine.

We report herein the asymmetric total synthesis of periglaucines A-C, N,O-dimethyloxostephine and oxostephabenine. The key strategies used include: 1) a RhI -catalyzed regio- and diastereoselective Hayashi-Miyaura reaction to connect two necessary fragments; 2) an intramolecular photoenolization/Diels-Alder (PEDA) reaction to construct the highly functionalized tricyclic core skeleton bearing a quaternary center; 3) a bio-inspired intramolecular Michael addition and transannular acetalization to generate the aza[4.4.3]propellane and the tetrahydrofuran ring.

Fabrication of ticagrelor bioadhesive solid dispersion based on coaxial electrostatic spray to improve drug release and enhance oral bioavailability.

Due to the low solubility and poor bioavailability of Ticagrelor (TIC), the current study developed a structured bioadhesive core-shell drug delivery system to address it. Ticagreior solid dispersion (T-SD) was fabricated using the uniaxial electrostatic spray method. Ticagrelor bio adhesive solid dispersion (T-BSD) was also prepared using the coaxial electrostatic spray technique. The adhesion of T-BSD to each intestinal segment was determined using biological adhesion test. The compartment model was used to study the plasma concentration-time curve and related pharmacokinetic parameters. The results of bioadhesion tests showed a positive adhesion effect of T-BSD in each intestinal segment. The maximum plasma concentration (Cmax) of T-BSD was increased to 777.08ng/mL compared with the free drug (367ng/mL). Similarly, t1/2, MRT and Tmax of T-BSD (12.1h, 9.4h, 4h) were higher than the free drug (11.2h, 8.6h, 1h), respectively. The relative bioavailability of T-BSD was further increased to 430% compared with the free drug. The findings collectively revealed that the coaxial-electrospray technique could be a promising way to improve the bioavailability of TIC.

Improved Core Viscosity Achieved by PDLLA10kCo-Incorporation Promoted Drug Loading and Stability of mPEG2k-b-PDLLA2.4k Micelles.

PURPOSE: This study aims to investigate the effect of poly(D, L-lactic acid)10K (PDLLA10K) incorporation on the drug loading and stability of poly(ethylene glycol)2K-block-poly(D, L-lactide)2.4K (mPEG2k-b-PDLLA2.4k) micelles. In addition, a suitable lyophilization protector was screened for this micelle to obtain favorable lyophilized products. METHODS: The incorporation ratios of PDLLA10k were screened based on the particle size and drug loading. The dynamic stability, core viscosity, drug release, stability in albumin, and in vivo pharmacokinetic characteristics of PDLLA10k incorporated micelles were compared with the original micelles. In addition, the particle size variation was used as an indicator to screen the most suitable lyophilization protectant for the micelles. DSC, FTIR, XRD were used to illustrate the mechanism of the lyophilized protectants. RESULTS: After the incorporation of 5 wt% PDLLA10K, the maximum loading of mPEG2k-b-PDLLA2.4k micelles for TM-2 was increased from 26 wt% to 32 wt%, and the in vivo half-life was increased by 2.25-fold. Various stability of micelles was improved. Also, the micelles with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as lyophilization protectants had minimal variation in particle size. CONCLUSIONS: PDLLA10k incorporation can be employed as a strategy to increase the stability of mPEG2k-b-PDLLA2.4k micelles, which can be attributed to the viscosity building effect. HP-ß-CD can be used as an effective lyophilization protectant since mPEG and HP-ß-CD form the pseudopolyrotaxanesque inclusion complexes.

The preparation and characterisation of tasteless core-shell clarithromycin microcapsules.

This study aims to fabricate core-shell clarithromycin (CAM) microcapsules to cover up the bitter taste of CAM by spray drying with aqueous polymer dispersion. Water dispersion of Eudragit EPO and Surelease® were innovatively used to encapsulate CAM into microcapsules via a one-step spray-drying method. The inlet air temperature, airflow rate, CAM-polymer ratio, and particle size of CAM were optimised based on drug content and T6% (the time taken for the drug to release equal to 6% w/w). The powder properties were assessed by measuring particle size and microstructure using SEM, FT-IR, and PXRD. Furthermore, selected batch was assessed for their drug content, encapsulation efficiency, in vitro release, bitterness, and stability studies. EPO-Surelease® (1: 4) microcapsules had an average diameter (D50) of 37.69 ± 3.61 µm with a span of 2.395. The drug contents and encapsulation efficiency of EPO-Surelease®(1:4) were 10.89% and 63.7%, respectively. EPO-Surelease® (1:4) microcapsules prepared by spray drying with aqueous polymer dispersion can effectively mask the bitter taste of CAM.

Physiological Adaptation Mechanisms to Drought and Rewatering in Water-Saving and Drought-Resistant Rice.

Water-saving and drought-resistant rice (WDR) has high a yield potential in drought. However, the photosynthetic adaptation mechanisms of WDR to drought and rehydration have yet to be conclusively determined. Hanyou 73 (HY73, WDR) and Huanghuazhan (HHZ, drought-sensitive cultivar) rice cultivars were subjected to drought stress and rewatering when the soil water potential was −180 KPa in the booting stage. The leaf physiological characteristics were dynamically determined at 0 KPa, −30 KPa, −70 KPa, −180 KPa, the first, the fifth, and the tenth day after rewatering. It was found that the maximum net photosynthetic rate (Amax) and light saturation point were decreased under drought conditions in both cultivars. The change in dark respiration rate (Rd) in HY73 was not significant, but was markedly different in HHZ. After rewatering, the photosynthetic parameters of HY73 completely returned to the initial state, while the indices in HHZ did not recover. The antioxidant enzyme activities and osmoregulatory substance levels increased with worsening drought conditions and decreased with rewatering duration. HY73 had higher peroxidase (POD) activity as well as proline levels, and lower catalase (CAT) activity, ascorbate peroxidase (APX) activity, malondialdehyde (MDA) level, and soluble protein (SP) content during all of the assessment periods compared with HHZ. In addition, Amax was markedly negatively correlated with superoxide dismutase (SOD), POD, CAT, and SP in HY73 (p < 0.001), while in HHZ, it was negatively correlated with SOD, CAT, APX, MDA, Pro, and SP, and positively correlated with Rd (p < 0.001). These results suggest that WDR has a more simplified adaptation mechanism to protect photosynthetic apparatus from damage in drought and rehydration compared with drought-sensitive cultivars. The high POD activity and great SP content would be considered as important physiological bases to maintain high photosynthetic production potential in WDR.

Alleviating the Influence of Circadian Rhythms and Drug Properties to the Release of Paliperidone Gel Matrix Tablets with Compression Coating Technology and Microenvironment Shaping.

The influence of circadian rhythms is an important content in oral dosage form study which is shown as different pH conditions and gastrointestinal dynamics in the gastrointestinal tract. The purpose of this study was to alleviate the influence of circadian rhythms and drug properties to the release of gel matrix tablets in vitro and in vivo. In this study, the compression coating technology and microenvironment shaping were utilized to achieve the alleviation of the influence of circadian rhythms and drug properties. The compression coating technology was used to alleviate the influence of gastrointestinal dynamics, and microenvironment shaping was used to alleviate the interference of different pH condition variations. The self-made compression coating tablet could maintain a consistent release rate in different pH conditions and different dynamic environments in vitro for 24 h. In vivo, the pharmacokinetic parameters Cmax and Tmax were 3701.675 ng/mL and 24 h, respectively, and the release effect in vivo was similar to the paliperidone osmotic pump tablet with the ability to alleviate the influence of circadian rhythms. The correlation coefficient R2 was 0.9914 for the self-made paliperidone compression coating tablet in vitro-in vivo correlation. The interference caused by circadian rhythms was alleviated so that the compression coating technology with microenvironment shaping could replace the osmotic pump technology with easier preparation process and cheaper costs in vitro and in vivo and achieve the effect of alleviating the interference of circadian rhythms.

Chitosan-Coated Liposomes: The Strategy to Reduce Intestinal Toxicity and Improve Bioavailability of Oral Vinorelbine.

In recent years, the oral administration of vinorelbine has gradually replaced intravenous administration in the treatment of several types of tumors. Even though the risk of phlebitis is avoided with oral administration, oral vinorelbine is still not a highly patient-compliant route due to the severe gastrointestinal toxicity. Vinorelbine-loaded liposomes with high encapsulation efficiency and suitable particle size were prepared using the ammonium sulfate gradient method. Chitosan-coated liposomes showed the slowest in vitro release compared to uncoated liposomes and vinorelbine solution. No damage was observed in the intestinal epithelial cells of mice orally administered with coated vinorelbine liposomes due to the low presence of the free drug in the gastrointestinal tract and the LD50 was increased from 129.83 to 182.25 mg/kg compared to oral vinorelbine solution. In addition, the positive surface potential of chitosan-coating endowed liposomes with mucosal adhesive function, delaying the time to reach the peak plasma concentration of vinorelbine from 1 to 4 h after administration. And bioavailability was increased to 2.1-fold compared to vinorelbine solution. In short, a new strategy to address the severe gastrointestinal side effects of oral vinorelbine has been developed.

Progesterone Phospholipid Gel for Intramuscular Administration Prepared by In Situ-Phase Separation.

Long-term daily injection of progesterone for the treatment of threatened abortion can be a source of considerable pain to patients. To reduce the frequency of injections and improve patient compliance, a novel injectable phospholipid-based phase separation gel (PPSG) was prepared using small molecular materials such as phospholipids, medium-chain triglycerides (MCTs), and ethanol. Progesterone was loaded into PPSGs to promote rapid gel formation in situ via a sol-gel transformation mechanism, thereby achieving a sustained controlled release. Furthermore, progesterone was distributed in the oil-water interface layer and within the oil phase. Solvent exchange drives phase transitions, and phospholipid vesicle formation and rupture are likely to promote drug release and gel degradation. At a drug loading of 140 mg/mL, a progesterone release of up to 60% could be reached within 9 days according to the release curve in vitro. Pharmacokinetic studies demonstrated that the progesterone-loaded PPSGs released the drug continuously for over 7 days, the half-life was eight times higher than that of progesterone oil solution, and relative bioavailability of up to 184.90% was obtained. Collectively, the sustained release properties for hydrophobic cargos would effectively enhance patient compliance. Moreover, PPSGs are promising drug delivery systems that have high market value and biosafety given the readily accessible and safe excipients.