Diagnostic Performance of Node Reporting and Data System Magnetic Resonance Imaging Score in Detecting Metastatic Cervical Lymph Nodes of Nasopharyngeal Carcinoma.

Background: The Node Reporting and Data System (Node-RADS) is a recently proposed classification system for the categorization of lymph nodes in radiological images. This study was conducted to retrospectively evaluate the diagnostic accuracy of the Node-RADS score for metastatic cervical lymph nodes on magnetic resonance imaging (MRI) of patients with nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed cervical lymph nodes of NPC cases. Two radiologists independently evaluated each lymph node on the MRI scans using Node-RADS. Interobserver agreement between 2 radiologists for Node-RADS score assessment was evaluated by linear weighted kappa statistics. The correlation between metastasis and the Node-RADS score of each lymph node was analyzed using multivariate regression analysis. To investigate the diagnostic performance of the Node-RADS score, we further conducted receiver operating characteristic curve analysis. Correspondently, the sensitivity, specificity, positive predictive value, and negative predictive value of each different cutoff (>1, >2, >3, and >4) were computed. Results: In all, 119 patients with NPC were assessed, including 203 cervical lymph nodes consisting of 140 (69%) of 203 metastatic and 63 (31%) of 203 benign. The kappa agreement between the 2 readers for the Node-RADS score was 0.863 (95% CI = 0.830-0.897, P < .001). Node-RADS score on MRI scan was shown to be an independent predictive factor of lymph node metastasis after multivariate regression analysis (odds ratio [OR] = 6.745, 95% CI = 3.964-11.474, P < .001). Node-RADS achieved an area under the curve (AUC) of 0.950 (95% CI = 0.921-0.979) in diagnosing metastatic lymph nodes. When Node-RADS >2 was identified as the best cutoff based on balanced values, the sensitivity and positive predictive value were 0.92 and 0.94, respectively. Conclusions: Our study suggests that the Node-RADS score has high accuracy in predicting NPC cervical lymph node metastasis. Nevertheless, this conclusion requires confirmation in a larger cohort of patients with NPC.

Design and Evaluation of Ginkgolides Gastric Floating Controlled Release Tablets Based on Solid Supersaturated Self-nanoemulsifying.

Ginkgolides are receptor antagonist of platelet activating factor with great clinical prospect, but its application is limited by its low solubility, short half-life and poor alkaline environment stability. It is difficult to solve these problems with a single drug delivery system. In this study, supersaturated self-nanoemulsifying gastric floating tablets of ginkgolides were developed through the combination of solid supersaturated self-nanoemulsifying drug delivery system (solid S-SNEDDS) and gastric retentive floating drug delivery system (GFDDS) to solve these problems of ginkgolides. Solid S-SNEDDS was prepared by D-optimal mixture design, normalization method and single factor experiment. The properties of solid-S-SNEDDS were studied by TEM, PXRD, FT-IR, SEM and in vitro drug release profile. Then, the optimal formulation of stomach floating tablet was obtained through single factor experiment and center composite design, followed by the study of in vitro release, model and mechanism of release, in vitro buoyancy and kinetics of erosion and swelling. PXRD and FT-IR showed that the drug in solid S-SNEDDS existed in an amorphous manner and formed hydrogen bond with excipients. The results showed that the cumulative release of GA and GB in the optimal tablets was 96.12% and 92.57% higher than the simple tablets within 12 h. The release mechanism of the tablet was skeleton erosion and drug diffusion. In 12 h, the optimal tablets can float stably in vitro and release the drug at a constant rate, with a cumulative release of more than 80%. In summary, the combination of SNEDDS and GFDDS is a promising means to solve the problems of ginkgolides.

The Modified Exenatide Microspheres: PLGA-PEG-PLGA Gel and Zinc-Exenatide Complex Synergistically Reduce Burst Release and Shorten Platform Stage.

The existing exenatide microspheres have the problem of burst release in the early stage, and minimal release in the middle stage which makes it difficult to achieve effective blood drug concentration (platform period). In this study, the modified exenatide microspheres were constructed to address the aforementioned issues. Poly(D,L-lactic-co-glycolic acid) (PLGA) and triblock copolymer with sol-gel conversion characteristics (PLGA-PEG-PLGA gel) were introduced as carriers to prepare microspheres. The hot gel characteristics and hydrophilicity of PLGA-PEG-PLGA gel were utilized to decline the burst release and shorten the platform period. Simultaneously, zinc acetate and exenatide were combined to generate an insoluble complex to further reduce the burst release. Herein, we prepared three types of exenatide microspheres using the solvent evaporation method and investigated their characterization as well as in vitro and in vivo release. According to the experimental findings, the modified exenatide microspheres, i.e., PLGA-PEG-PLGA gel and PLGA co-loaded zinc-exenatide insoluble complex microspheres (Zn-EXT-Gel-MS), had smooth and rounded surfaces, with a particle size of 24.7 µm, and the encapsulation rate reached 89.43%. And it was released for 40 days in vitro, behaving better than the other two microspheres in terms of release behavior. When this product was administered subcutaneously to rats, it produced a comparatively constant plasma exenatide concentration that lasted for 24 days and superior bioavailability than the exenatide microspheres (EXT-MS). The creation of modified exenatide microspheres may serve as a heuristic method for other long-acting medications. Schematic diagram of the synthesis process and release curves of three types of exenatide microspheres in vitro and in vivo.

Study of vascular sclerosing agent based on the dual mechanism of vascular endothelial cell damage-plasmin system inhibition.

Venous malformations are a vascular disorder. Currently, the use of chemical sclerosing agents is a common clinical approach for the treatment of venous malformations. However, the effectiveness of existing sclerosing agents is unsatisfactory and often accompanied by severe side effects. In this study, we have developed a novel cationic surfactant-based sclerosing agent (POL-TA) by conjugating the plasmin inhibitor tranexamic acid (TA) with a nonionic surfactant polidocanol (POL) through an ester bond. POL-TA induces endothelial cell damage, triggering the coagulation cascade and thrombus formation. Moreover, it releases TA in vivo, which inhibits plasmin activity and the activation of matrix metalloproteinase (MMPs), thereby stabilizing the fibrin network of the thrombus and promoting vascular fibrosis. We have established a cell model using venous malformation endothelial cells and assessed the cellular damage and underlying mechanisms of POL-TA. The inhibitory effects of POL-TA on the plasmin-MMPs system were evaluated using MMP-9 activity assay kit. Additionally, the mice tail vein model was employed to investigate the vascular sclerosing effects and mechanisms of POL-TA.

The association of living alone and social isolation with sarcopenia: A systematic review and meta-analysis.

BACKGROUND: Living alone can cause social isolation and is correlated with multiple adverse health outcomes. Evidence about the association of living alone and social isolation with sarcopenia is limited. This meta-analysis aims to investigate the correlation between living alone, social isolation, and sarcopenia. METHODS: According to the PRISMA guidelines, we systematically searched Medline, Embase, Web of Science, and Scopus for literature published up to June 30, 2023. We conducted reference checking to supplement the references. Two investigators independently screened the references for eligibility and assessed the quality of the references. We included references involving data on living alone, social isolation, and sarcopenia. Two investigators recorded study data for meta-analysis and study characteristics. RESULTS: Data regarding living alone and sarcopenia were available from 13 studies. Meta-analysis demonstrated that living alone is correlated with sarcopenia (odds ratio, 1.51; 95 % CI, 1.31-1.75; p < 0.001). The gender-stratified analysis demonstrated that women living alone are more likely to have sarcopenia (odds ratio, 1.81; 95 % CI, 1.32-2.48; p < 0.001) but not men (odds ratio, 1.24; 95 % CI, 0.56-2.74; p = 0.60). Data regarding social isolation and sarcopenia were available from five studies. Social isolation is also associated with sarcopenia (odds ratio, 1.70; 95 % CI, 1.51-1.92; p < 0.001). And subgroup analysis demonstrated that social isolation is a risk factor for sarcopenia (odds ratio, 1.79; 95 % CI, 1.55-2.06; p < 0.001). CONCLUSIONS: This meta-analysis revealed the association of living alone and social isolation with sarcopenia. Gender differences can help to screen high-risk groups of sarcopenia and reduce healthcare expenditures. As a further development of living alone, social isolation may play a more important role in sarcopenia than living alone.

Application of Artificial Intelligence to the Diagnosis and Therapy of Nasopharyngeal Carcinoma.

Artificial intelligence (AI) is an interdisciplinary field that encompasses a wide range of computer science disciplines, including image recognition, machine learning, human-computer interaction, robotics and so on. Recently, AI, especially deep learning algorithms, has shown excellent performance in the field of image recognition, being able to automatically perform quantitative evaluation of complex medical image features to improve diagnostic accuracy and efficiency. AI has a wider and deeper application in the medical field of diagnosis, treatment and prognosis. Nasopharyngeal carcinoma (NPC) occurs frequently in southern China and Southeast Asian countries and is the most common head and neck cancer in the region. Detecting and treating NPC early is crucial for a good prognosis. This paper describes the basic concepts of AI, including traditional machine learning and deep learning algorithms, and their clinical applications of detecting and assessing NPC lesions, facilitating treatment and predicting prognosis. The main limitations of current AI technologies are briefly described, including interpretability issues, privacy and security and the need for large amounts of annotated data. Finally, we discuss the remaining challenges and the promising future of using AI to diagnose and treat NPC.

A copper nanocluster-based multifunctional nanoplatform for augmented chemo/chemodynamic/photodynamic combination therapy of breast cancer.

With the development of nano drug delivery system, the treatment mode that can overcome the shortcomings of chemotherapy drugs and integrate combined therapy remains to be explored. Herein, a nano drug system was designed to achieve the combined effect of chemo/chemodynamic/photodynamic therapy on cancer. Specifically, copper clusters (CuNCs) were used as the carrier, hyaluronic acid (HA) and doxorubicin (DOX) were coupled on CuNCs and then and chlorin e6 (Ce6) was introduced to form the self-assembled HA-CuNCs@DC nanoparticles. In this system, the HA-CuNCs@DC was involved in the reaction to the acidic tumor microenvironment (TME)-release of DOX, which could not only inhibit tumor growth through chemotherapy, but enhance the generation of hydrogen peroxide. CuNCs carriers had the properties of Fenton-like activity to realize chemodynamic therapy (CDT) and oxidase-like activity to deplete intracellular glutathione (GSH). Additionally, the chemotherapy drug susceptibility increased owing to the GSH depletion and the outbreak of reactive oxygen species, indicating the enhanced CDT efficacy and amplified chemotherapy efficacy. It was also noteworthy that Ce6 could be activated by 660 nm light to produce abundant singlet oxygen for photodynamic therapy. Overall, our platform demonstrated excellent biosafety and tumor suppression capabilities. This multimodal theranostic strategy provided new insights into cancer therapy.

Preparation and Evaluation of Novel Supersaturated Solid Dispersion of Magnolol : Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability.

This article aimed to design a new type of supersaturated solid dispersion (NS-SD) loaded with Magnolol (Mag) to raise the oral bioavailability in rats. In the light of the solubility parameters, phase solubility experiments, inhibition precipitation experiment, and in vitro release experiment, Plasdone-630 (PS-630) was selected as the optimum carrier. In addition, Mag-NS-SD was prepared by adding Monoglyceride (MG) and Lecithin High Potency (LHP) into the Mag-S-SD (Mag:PS-630 = 1:3), so as to reduce the dosage of carrier and improve the release rate. Using central composite design of response surface method, the prescription was further optimized. As the optimized condition was Mag:PS-630: MG: LHP = 1:3:0.8:0.266, the drug release rate was the fastest. Besides, after 45 min, the release rate was nearly 100%. The constructed Mag-S-SD and Mag-NS-SD were characterized by powder X-ray diffraction and infrared absorption spectrum. The XRD patterns of Mag-S-SD and Mag-NS-SD indicated that all APIs were amorphous. The IR spectra of Mag-S-SD and Mag-NS-SD demonstrated the existence of hydrogen bonding in the systems. Furthermore, in vivo pharmacokinetic study in rats revealed that compared with Mag and Mag-S-SD, Mag-NS-SD significantly increased the bioavailability (the relative bioavailability was 213.69% and 142.37%, separately). In this study, Mag-NS-SD was successfully prepared, which could improve the oral bioavailability and may increase the clinical application.

Integrated in silico formulation design of self-emulsifying drug delivery systems.

The drug formulation design of self-emulsifying drug delivery systems (SEDDS) often requires numerous experiments, which are time- and money-consuming. This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches. 4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods. Random forest (RF) showed the best prediction performance with 91.3% for accuracy, 92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation. The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy (89.51%). The central composite design (CCD) was used to screen the best ratio of oil-surfactant-cosurfactant. Finally, molecular dynamic (MD) simulation was used to investigate the molecular interaction between excipients and drugs, which revealed the diffusion behavior in water and the role of cosurfactants. In conclusion, this research combined machine learning, central composite design, molecular modeling and experimental approaches for rational SEDDS formulation design. The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine.

The aim of this article was to design a self-emulsifying drug delivery system (SEDDS) of loaded cepharanthine (CEP) to improve the oral bioavailability in rats. Based on the solubility determination and pseudo-ternary phase diagram, isopropyl palmitate (IPP) was chosen as the oil phase. Meanwhile, Cremophor RH40 and Macrogol 200 (PEG 200) were chosen as the emulsifier and co-emulsifier, respectively. This prescription was further optimized by using central composite design of response surface methodology. The optimized condition was CEP:IPP:Cremophor RH40:PEG 200=3.6:30.0:55.3:11.1 in mass ratio with maximum drug loading (36.21 mg/mL) and the minimum particle size (36.70 nm). The constructed CEP-SEDDS was characterized by dynamic light scattering, transmission electron microscopy, in vitro release and stability studies. The dissolution level of CEP-SEDDS was nearly 100% after 30 min in phosphate-buffered saline (PBS, pH 6.8) which was higher than that of the pure CEP (approximately 20%). In addition, in vivo pharmacokinetic study in rats showed that CEP-SEDDS dramatically improved bioavailability compared with active pharmaceutical ingredient (API) (the relative bioavailability was 203.46%). In this study, CEP-SEDDS was successfully prepared to enhance the oral bioavailability which might facilitate to increase its better clinical application. Graphical abstract.

Osmotic pump tablets with solid dispersions synergized by hydrophilic polymers and mesoporous silica improve in vitro/in vivo performance of cilostazol.

The purpose of this study is to improve in vitro dissolution and in vivo bioavailability of the poorly soluble drug cilostazol (CLT) through amorphous solid dispersion technology, and this study prepared a stable supersaturated drug-loaded system to improve the problem of high free energy and instability of traditional solid dispersions. The optimized formulation of the solid dispersion is CLT: Syloid®244FP: Kolliphor®P188 = 1:1.5:1.5 (CLT-SD), where the co-loading of Syloid®244FP and Kolliphor®P188 has the synergistic effect. Drug polymers interactions and drug morphology were estimated by the physicochemical characterization, including DSC XRD, SEM, TEM, FT-IR, and Specific area analysis. Optimized formulation kept most drug in an amorphous state without significant change in dissolution, which could be maintained for at least 1 year. The solid dispersion was further prepared into osmotic pump tablets for the purpose of the controlled-release of drugs. The bioavailability of the three preparations (CLT, CLT-SD, osmotic pump tablets) was evaluated in Beagle dogs, which results clarified that the oral bioavailability of CLT-SD improved as compared with the CLT powder and osmotic pump tablets achieved controlled-release of drugs. In conclusion, co-loading drugs with mesoporous silica and hydrophilic polymer compounds can be a guiding future modification method for delivering supersaturated drug loading systems.

99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation.

BACKGROUND: Emerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)-loaded nanoparticle of 99mTc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics. MATERIALS AND METHODS: The synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice. RESULTS: HA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 µg/mL, compared with free curcumin (77 µg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99mTc. The SPECT images showed that 99mTc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85±0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs. CONCLUSION: The results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99mTc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.

Transferrin Modified Dioscin Loaded PEGylated Liposomes: Characterization and In Vitro Antitumor Effect.

In this study, a novel transferrin modified liposomal dioscin was prepared by the film dispersion method. The transferrin modified dioscin loaded liposomes (Tf-Lip/Dio) were near-spherical in morphology and had an average particle size of 140.07±1.33 nm, a narrow polydispersity index of <0.2 and a relatively stable zeta potential of -23.7±1.16 mV. The drug entrapment efficiency (EE) and drug loading (DL) of Tf-Lip/Dio were 88.94±1.02% and 4.16±0.05%, respectively. Tf-Lip/Dio exhibited a sustained release characterization of approximately 30% of the total dioscin content after 72 h at 37 °C. Tf-Lip/Dio showed higher cytotoxic efficacy after incubation for 24 h in both HeLa cells and HepG2 cells than in nonmodified liposomes. The enhanced antitumor activity of Tf-Lip/Dio might be due to the increased intracellular uptake, which was corroborated by laser scanning confocal microscopy and flow cytometry. Furthermore, hemolysis experiments preliminarily verified the safety of its intravenous injection. Overall, this study demonstrates Tf-Lip/Dio to be a favorable delivery vehicle for dioscin in future cancer therapy.

Self-assembled liposome from core-sheath chitosan-based fibres for buccal delivery of carvedilol: formulation, characterization and in vitro and ex vivo buccal absorption.

OBJECTIVES: A novel drug delivery system based on self-assembled liposome from core-sheath nanofibres for buccal delivery of Carvedilol (Car) was explored. METHODS: The Car-loaded PVP/PC (phospholipids) layer was coated with chitosan-PVA (CS-PVA) or CS-PVP to increase retention period in the mouth. SEM, confocal laser scanning microscopy (CLSM), XRD and Fourier transform infrared spectroscopy were applied to characterize fibre diameter and drug state. Appearance, particle size and encapsulation efficiency of self-assembled liposome were investigated by transmission electron microscopy (TEM) and Zeta-sizer Nano. The dissolution test and permeation tests across porcine buccal mucosa and TR146 cell model also were run. KEY FINDINGS: Confocal laser scanning microscopy and XRD confirmed the core-sheath structure of coaxial fibre and non-crystalline form of Car, separately. TEM demonstrated the sphere morphology of self-assembled liposome from spun fibres after contacting water. The dissolution test implied the ratio of PC to Car had a huge impact on drug release. The permeation tests across porcine buccal mucosa and TR146 cell model showed similar result, namely our formulation having a better permeation performance than Car suspension. The indirect toxicity against TR146 cells presented 5 mg/ml (or lower) of fibre extraction was safe for cells. CONCLUSIONS: These researches exhibited this drug delivery system was promising and advantageous for Car buccal delivery.

Thermal Extrusion 3D Printing for the Fabrication of Puerarin Immediate-Release Tablets.

Thermal extrusion (TE) 3D printing is a thermoplastic semisolid-based rapid prototyping process, which is capable of building complex structures. The aim of this study was to manufacture rapid-release puerarin tablets without solvent through TE 3D printing. Novel rapid-release tablets were fabricated with polyethylene glycol (PEG 4000) as the carrier at appropriate puerarin/PEG 4000 ratios, assessed through differential scanning calorimetry (DSC), solubility, and dissolution tests. The novel structures of 3D-printed tablets with five different values were formed by printing paths, which established a flexible way of adjusting in vitro drug release. An obvious acceleration (85% of cumulative release about 7.5 min at the soonest) was observed for the tablets with internal structural design. It was inferred that puerarin formed simple eutectic mixtures with PEG 4000 and that puerarin dispersed into the carrier based on DSC and X-Ray powder diffraction (XRD). This highlights the combined advantage of PEG as a soluble polymer with TE 3D printing and provides a suitable system for rapid puerarin release.

Preparation and Evaluation of mPEG-PLGA Block Copolymer Micelles Loaded with a Sarsasapogenin Derivative.

Sarsasapogenin derivative 5n (SGD 5n) is a new compound with potent antitumor efficacy, but the low solubility severely affects its absorption and bioavailability. Therefore, the SGD 5n-loaded mPEG-PLGA block copolymer micelles were developed to improve the value of SGD 5n in clinical application. The polymeric micelles were prepared by an organic solvent evaporation method, and the encapsulation efficiency (EE), drug loading (DL), critical micelle concentrations (CMC), morphology, particle size, and zeta potential were determined. The cytotoxicity was examined by the MTT assay, and the cellular uptake study was performed by confocal laser scanning microscopy. A model of tumor-bearing mouse was established to study the antitumor activity in vivo. The results demonstrated that the particle size of the prepared micelle was 124.6 ± 9.6 nm, the encapsulation efficiency was 82.0 ± 2.9%, and the drug loading was 8.3 ± 0.4%. The results of cytotoxicity and cellular uptake demonstrated that the SGD 5n-loaded micelles could efficiently enter tumor cells, and the cellular uptake of SGD 5n presented concentration and time dependence. This study demonstrated that the prepared SGD 5n-loaded polymeric micelles had significant antitumor activity and provided a basis for clinical development of new compound SGD 5n.

Flexibility of 3D Extruded Printing for a Novel Controlled-Release Puerarin Gastric Floating Tablet: Design of Internal Structure.

The objective of this study was to investigate the development of a novel puerarin gastric floating system with a concentric annular internal pattern by a 3D extrusion-based printing technique and to explore the flexibility of turning the release behavior through the design of the internal structure. The composition consisted of the conventional sustained-release pharmaceutical excipients without addition of foaming agent or light materials. First, the proper alcohol/water proportion was selected for the binding agent. The desired drug release behaviors and good floating properties were obtained either through modification of the formulation composition or adjustment of the internal structure. In vitro, the printed tablets were evaluated for drug release, mechanical properties, lag time, and floating duration time. The in vivo behaviors of the formulations were noted at certain time intervals through assessment of the radiographic pictures of healthy volunteers. The gastric retention time in the 3D-printed tablet was approximately 6 h in vivo. Results indicated these puerarin gastric floating 3D-printed tablets had great potential to achieve good gastric residence time and controlled release. Therefore, 3D extrusion-based printing appears to be appropriate for the production of oral administration systems, owing to its flexibility and the great floating ability and controlled-release capacity of its products.

Two types of core/shell fibers based on carboxymethyl chitosan and Sodium carboxymethyl cellulose with self-assembled liposome for buccal delivery of carvedilol across TR146 cell culture and porcine buccal mucosa.

Two novel core-shell fibers which could self-assemble liposome were fabricated based on bioadhesive polymer carboxymethyl chitosan (CMCS) and Sodium carboxymethyl cellulose (CMC-Na), separately. The shell layers were CMCS/PVA and CMC-Na/PVA, respectively, and the core layer was mixture of PVP, Phospholipids (PC) and Carvedilol (Car). The diameter distribution and core/shell structure were examined by SEM and CLSM. FTIR and XRD were also used to characterize the fiber. Self-assembled liposome was observed by TEM, and other parameters like drug encapsulation efficiency was also determined. In vitro adhesive force was conducted to evaluate bioadhesive property of fibers. Dissolution test demonstrated Car was almost completely released within 2 h and presented linear release. The permeation studies across porcine TR146 cell culture and buccal mucosa were carried out, indicating self-assembled liposome and bioadhesive polymer both promoted drug penetration. MTT test showed TR146 cells were safe after incubation with fibers' extraction medium under the concentration of 10 mg/mL. In summary, this design based on self-assembled liposome and core/shell fiber using water-soluble bioadhesive polymer was desirable for Car buccal absorption.

Structure-Based Gastro-Retentive and Controlled-Release Drug Delivery with Novel 3D Printing.

In the present contribution, the aim is to explore and establish a way in which 3D printing and gastro-retentive drug delivery systems (GRDDSs) are combined (focusing on inner structure innovation) to achieve extended and stable gastro-retention and controlled-release of drug. Three digital models diverse in construction were designed and substantialized by a pressure-assisted microsyringe (PAM) 3D printer. Preparations were characterized by means of DSC, XRD, FTIR, and SEM. In vitro buoyancy study and in vivo gamma scintigraphy method were conducted to validate gastro-retention property of these innovative preparations in vitro/in vivo respectively. Release kinetic model was established and release mechanism was discussed. Tablets manufactured under certain range of parameters (intersecting angle, full filling gap) were tight and accurate in shape. Tablets printed with specific parameters (full filling gap, 50%; nozzle extrusion speed, 0.006 mm/s; layer height, 0.4 mm; compensation value, 0.25; quantity of layers, 15; outline printing value, 2) exhibited satisfactory in vitro (10-12 h)/in vivo (8-10 h) retention ability and possessed stable 10-12 h controlled-release quality. In general, 3D printing has tremendous advantage over conventional fabrication technique in intricate drug delivery systems and will be widely employed in pharmacy.