Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.
Administration, Cutaneous ; Chromatography, Liquid ; Emulsions ; Permeability ; Skin/metabolism* ; Skin Absorption ; Tandem Mass Spectrometry

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.
Administration, Oral ; Biological Availability ; Caco-2 Cells ; Drug Delivery Systems ; Emulsions ; Humans ; Methylcellulose/analogs & derivatives* ; Nanoparticles ; Particle Size ; Silybin ; Solubility

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.
Administration, Cutaneous ; Animals ; Drug Liberation ; Emulsions ; Gels ; Glycyrrhiza ; Mice ; Skin Absorption

Intestinal hypoganglionosis is a rare innervation disorder that provides numerous nutritional, medical and surgical challenges. In this case report, we present a case of a newborn with intestinal hypoganglionosis leading to intestinal failure and intestinal failure-associated liver disease who responded to Omegaven™, a fat emulsion comprised of omega-3 fatty acids. Omegaven™ has been shown to be beneficial in the management of cholestatic liver injury. Clinical success with Omegaven™ was seen in this patient with a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and complete resolution of cholestasis with a direct bilirubin of zero within two weeks of initiation of Omegaven™. No current guidelines for the diagnosis and management of hypoganglionosis are available. We recommend a multidisciplinary approach and the use of novel therapies such as fat emulsions composed of omega-3 fatty acids for improved patient outcomes. Appropriate compassionate use protocols should be obtained from the Food and Drug Administration prior to initiation of Omegaven™.
Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Bilirubin ; Cholestasis ; Compassionate Use Trials* ; Diagnosis ; Empathy* ; Emulsions ; Fatty Acids, Omega-3 ; Hirschsprung Disease ; Humans ; Infant, Newborn ; Liver ; Liver Diseases ; Parenteral Nutrition, Total ; United States Food and Drug Administration

To explore the effect of long-time propofol infusion on myocardial enzymes, mitochondrial cytochrome C and ATP in rabbits. 
 Methods: A total of 18 New Zealand rabbits were randomly divided into 3 groups: a control group, a propofol group and an intralipid group. The rabbits were continuously infused with 0.9% normal saline in the control group, 1% propofol in the propofol group, and 10% intralipid in the intralipid group, respectivey. The arterial blood was collected at 0, 8, 16 h and the end of experiment to examine creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the end, the myocardial mitochondria from myocardial tissues was separated by differential centrifugation, and mitochondrial cytochrome C content and adenosine triphosphate (ATP) levels were examined by high performance liquid chromatography.
 Results: Compared with the control group, the release of cytochrome C from mitochondria were increased in the propofol group and the intralipid group (both P<0.05), but there was no significant difference between them (P>0.05). There was also no significant difference in the ATP content of the mitochondria among the 3 groups (P>0.05). The levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group compared with that before the infusion (all P<0.05); compared with the control group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group (all P<0.05); compared with the intralipid group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group (all P>0.05); compared with the control group, the levels of CK-MB were obviously increased in the infusion of propofol for 24 h in the propofol group (P<0.05).
 Conclusion: The levels of serum CK increase after the infusion of propofol and intralipid for a long time, and the levels of CK-MB also elevate in the infusion of propofol. Propofol and intralipid can increase the release of myocardial mitochondrial cytochrome C, but they don't affect the ATP production in myocardial mitochondrial.
Adenosine Triphosphate ; metabolism ; Animals ; Creatine Kinase ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Cytochromes c ; metabolism ; Emulsions ; administration & dosage ; pharmacology ; Infusions, Intravenous ; Mitochondria ; drug effects ; Myocardium ; chemistry ; enzymology ; Phospholipids ; administration & dosage ; pharmacology ; Polyphosphates ; Propofol ; administration & dosage ; pharmacology ; Rabbits ; Soybean Oil ; administration & dosage ; pharmacology

Based on the demand of nasal drug delivery high drug loadings, using the unique phase transfer of solute, integrating the phospholipid complex preparation and submicron emulsion molding process of Scutellariae Radix extract, the study obtained the preparation of the high drug loadings submicron emulsion of Scutellariae Radix extract. In the study of drug solution dispersion method, the uniformity of drug dispersed as the evaluation index, the traditional mixing method, grinding, homogenate and solute phase transfer technology were investigated, and the solute phase transfer technology was adopted in the last. With the adoption of new technology, the drug loading capacity reached 1.33% (phospholipid complex was 4%). The drug loading capacity was improved significantly. The transfer of solute method and timing were studied as follows,join the oil phase when the volume of phospholipid complex anhydrous ethanol solution remaining 30%, the solute phase transfer was completed with the continued recycling of anhydrous ethanol. After drug dissolved away to oil phase, the preparation technology of colostrum was determined with the evaluation index of emulsion droplet form. The particle size of submicron emulsion, PDI and stability parameters were used as evaluation index, orthogonal methodology were adopted to optimize the submicron emulsion ingredient and main influential factors of high pressure homogenization technology. The optimized preparation technology of Scutellariae Radix extract nasal submicron emulsion is practical and stable.
Administration, Intranasal ; Emulsions ; Plant Extracts ; Technology, Pharmaceutical ; methods

An HPLC method for the determination of geniposide concentration in mouse plasma was developed and the pharmacokinetics after intranasal administration of Xingnaojing microemulsion (XNJ-M) and mPEG2000-PLA modified Xingnaojing microemulsion (XNJ-MM) were investigated. Eighty mice were treated by XNJ-M and XNJ-MM nasally. The plasma samples were collected at different times and the drug in samples was detected by HPLC. The pharmacokinetic parameters were calculated by the software of Kinetica. The pharmacokinetic parameters of geniposide of XNJ-M were C(max) (4.36 +/- 2.69) mg x L(-1), t(max) 1 min, MRT (29.73 +/- 4.54) min, AUC (53.63 +/- 14.03) mg x L(-1) x min. The pharmacokinetic parameters of geniposide of XNJ-MM were C(max) (9.75 +/- 4.14) mg x L(-1), t(max) 1 min, MRT(22.34 +/- 2.90) min, AUC (131.87 +/- 40.13) mg x L(-1) x min. Geniposide can be absorbed into blood in a higher degree after intranasal administration with XNJ-MM compared to XNJ-M, which maybe caused by its less irritating and more absorption.
Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Emulsions ; Iridoids ; blood ; pharmacokinetics ; Lactic Acid ; chemistry ; Male ; Mice ; Polyesters ; Polyethylene Glycols ; chemistry ; Polymers ; chemistry

With the deepening of modernization of traditional Chinese medicine (TCM) and continuing emergence of new theories, methods and techniques, a very rapid and significant development has been achieved in the pharmacokinetics (PK) of TCM. This paper reviews the main research progresses of PK of TCM, including integrated PK of multiple effective components of TCM, fingerprint PK of TCM, novel dosage form PK of TCM, polysaccharide PK of TCM and drug interactions of TCM; and further sets up the prospects.
Animals ; Drug Combinations ; Drug Interactions ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; chemistry ; isolation & purification ; pharmacokinetics ; Emulsions ; pharmacokinetics ; Humans ; Liposomes ; pharmacokinetics ; Medicine, Chinese Traditional ; methods ; Nanostructures ; Plants, Medicinal ; chemistry ; Polysaccharides ; pharmacokinetics