AIM: To study the formulation and preparation factors on vitro drug release from sinomenine hydrochloride delayed-onset sustained-release tablet. METHODS: With hydrophilic matrix materials as excipient,the tablets containing hydrochloride sinomenine as a model drug were prepared by direct compression. The effect of the type and amount of tablet core matrix materials(HPMC K15M,HPMC K4M,xanthan gum and carrageenan),the type and amount of coating matrix materials,the preparation of coating materials and the pressure on in vitro drug release of the tablets were studied. RESULTS: The lag time of the tablet was 4 ～ 5 h and drug release slowly in 24 h. The type and the amount of the core matix materials and the coating matrix materials play an important role on lag time and drug release(P

AIM : To prepare a phase-specific drug delivery system withfloating and pulsatile release of sinome-nine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics. The effects of factors influencing release characteristic of the drug were investigated by dissolution test, and to elucidate the mechanism of drug releaseof the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release. The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer. The lag-time was prolonged with the increase of pH and ionic strength of dissolution media.CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.

AIM: To prepare a phase-specific drug delivery system with floating and pulsatile release of sinomenine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics.The effects of factors influencing release characteristic of the drug were investigated by dissolution test,and to elucidate the mechanism of drug release of the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release.The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer.The lag-time was prolonged with the increase of pH and ionic strength of dissolution media. CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.

Aim To investigate the effect of resveratrol on proliferation and differentiation in K562 cells. Methods K562 cells were treated with different con-centrations of resveratrol for 6d. The colony number of K562 cells was detected with semi-solid culture assay. Expression of GATA-1 and PU. 1 in K562 cells was re-spectively measured with immunocytochemistry and Western blot. Expression of differentiation related anti-gen, CD11b, CD14 and CD42b, was measured with flowcytometry on K562 cells. Results Resveratrol
could significantly decrease the colony number of K562 cells in a dose-dependent manner, and enhance the ex-pression of GATA-1,PU. 1,CD11b, CD14 and CD42b in K562 cells. Conclusion Resveratrol could inhibit the proliferation and induce differentiation of K562 cells via up-regulating the expression of GATA-1 and PU. 1 protein.

OBJECTIVE:To establish the mesoporous carbon nano-drug delivery system (MCNs) with chemotherapy drugs loaded and holding photothermal and photodynamic combined effect,and study its anti-multidrug-resistant tumor effect in vitro. METHODS:MCNs was prepared by low-concentration hydrothermal route,and the MCNs surface was carboxylated by the mixed acid ultrasound method to made MCNs-COOH (MCNC). The morphology and surface properties were evaluated. Adriamycinc (ADR)was loaded into MCNC to fabricate ADR/MCNC via adsorption method. Drug loading capacity was calculated by UV,and drug release profile was investigated by dialysis method. ADR-resistant human breast cancer MCF-7/ADR cells were chosen,and cell uptake and positioning of ADR/MCNC were observed by confocal laser microscopy;cytotoxicity of ADR/MCNC was detected by MTT method;and intracellular reactive oxygen species(ROS)level under NIR irradiation was measured by flow cytometry. RE-SULTS:The particle size of prepared MCNs was about 90 nm,with carboxyl in surface. The specific surface area was 541.62 m2/g,pore volume was 0.34 cm3/g,and pore size distribution was 2.5 nm,with significant photothermal effect. The drug loading ca-pacity of ADR/MCNC was 47.4%,showing pH/NIR responsiveness release characteristics. It can promote ADR in cell uptake and nuclear accumulation and induce MCF-7/ADR cell to generate ROS under NIR irradiation,with significant inhibitory effect. CON-CLUSIONS:MCNs is prepared successfully,and ADR/MCNC has an effect on anti-multidrug-resistant tumors.

OBJECTIVE:To prepare the Indocyanine green gold nanocages(ICG/Biotin-PEG-AuNC-PCM),and study its anti-tumor activity. METHODS:Polyol reduction method was used to prepare silver nanometer cubes (AgNC) as template,ion ex-change reaction was used to prepare gold nanocages (AuNC) to characterize its morphology,particle size,near infrared (NIR) light and heat properties. Organic solvent evaporation method was conducted to prepare the ICG/Biotin-PEG-AuNC-PCM loaded with ICG,1-tetradecanol(PCM),surface modification of biotin polyethylene glycol mercapto(Biotin-PEG-SH). Its particle size, polydispersity index (PDI) and drug loading were detected,and in vitro cumulative release (Q) within 180 min under 37,40 ℃was investigated. Using adriamycin-resistant human breast cancer cells(MCF-7/ADR cells)as objects,MTT method was used to in-vestigate the antitumor activities of ICG,ICG/PEG-AuNC-PCM and ICG/Biotin-PEG-AuNC-PCM,and half inhibitory concentra-tion(IC50)was calculated. RESULTS:AuNC was cubic with particle size of about 60 nm and good light and heat properties. The particle size of ICG/Biotin-PEG-AuNC-PCM was(105±2.8)nm,PDI was 0.261±0.02(n=3). Drug loading was 1.34×108 g/mol AuNC,Q180 min was about 10%under 37℃and Q20 min was about 80%under 40℃. IC50 of ICG,ICG/PEG-AuNC-PCM and ICG/Bi-otin-PEG-AuNC-PCM on MCF-7/ADR cells was 95.2, 29.3, 16.1 μg/mL, respectively. CONCLUSIONS:ICG/Biotin-PEG-AuNC-PCM is successfully prepared,and the antitumor activity on MCF-7/ADR cells is stronger than ICG.

AIM:To investigate the effect of decitabine (Dacogen, DAC) on the proliferation and differentia-tion of K562 cells.METHODS:The K562 cells were treated with different concentrations of DAC .The colony formation ability of the cells was detected by the colony formation assay with semi-solid culture .The cell viability was detected with MTT assay.The morphologic features were observed under inverted microscope with Wright ’s staining.The changes of the cell cycle distribution and the expression of CD 11b and CD42b were analyzed with flow cytometry .The protein expression of CDK2, cyclin E1, P27, GATA-1 and PU.1 in the K562 cells was determined by Western blot .RESULTS:DAC signifi-cantly decreased the colony number of the cells and cell viability in a dose-dependent manner .The morphological changes of the cells displayed partial differentiation .After treated the K562 cells with DAC for 72 h, the cell proportion in S phase was obviously decreased , while the cell proportion in G 2/M phase was obviously increased in a dose-dependent manner . After treated the K562 cells with DAC for 7 d, the percentage of CD11b and CD14 positive cells was further elevated , and the protein expression of P27, GATA-1 and PU.1 was increased.However, the protein expression of CDK2 and cyclin E1 was decreased .CONCLUSION:DAC inhibits the proliferation and induces differentiation of the K 562 cells via regulation of cell cycle .

OBJECTIVETo prepare sinomenine hydrochloride delayed-onset sustained-release tablets.

METHODThe tablets containing sinomenine hydrochloride were prepared by dry-compression coating technique with the ratio of HPMC in core tablet and the ratio of HPMC in coating film as the influence factors and the lag-time and release rate as the evaluation parameters. Experiments were done on the central composite design, the data were simulated by using multi-linear equation and second-order polynomial equation. The possibly optimal formulation was predicted by response surface method. The dissolution date (lag-time and release rate) of the tablets prepared under the optimum condition were compared with the predicted. The drug released mechanism of the tablet were studied by Model-fitted of drug released within 6-15 h with zero-order, Higuchi and Peppas equation, respectively.

RESULTThe lag-time and release rate were simulated using second-order polynomial equation, regression coefficients of the two parameters were 0.9901 and 0.9876, respectively. Bias between the observed and predicted values of lag-time and release rate were -3.15% and -0.34%, respectively. The lag-time of the tablet prepared under the optimum condition in vitro was about 6 h, then drug released from the tablet within 6-15 h was found to conform to zero-order kinetics and was controlled by bulk erosion mechanism.

CONCLUSIONSinomenine hydrochloride delayed-onset sustained-release tablets release drug slowly after lag time. The models developed in this study are proved to be highly predictable.

Chemistry, Pharmaceutical ; Delayed-Action Preparations ; administration & dosage ; Drug Delivery Systems ; methods ; Excipients ; administration & dosage ; Morphinans ; administration & dosage ; Pharmaceutical Preparations ; administration & dosage ; Tablets ; administration & dosage ; Technology, Pharmaceutical

Objective To explore the effect of blood circulation punching apparatus on important vital signs and thrombus of lower extremity veins in stable blood pressure and normal cardiopulmonary function patients with cerebrovascular disease and hypertension and to evaluate safety and effectiveness of the apparatus for these patients.Methods We treated 30 patients with cerebrovascular disease and hypertension by blood circulation punching apparatus for 3 days,2 times per day,30 minutes per time.We monitored vital signs of these patients 15 minutes pre-,intra-and post-treatment.The thrombus of lower extremity veins and adverse reactions were observed during the treatment.Results We compared systolic pressure,diastolic pressure,pulse and breathe of patients 15 minutes pre-,intra-and post-treatment respectively.We didn't find any significant differences between these parameters.No patient had thrombus of lower extremity veins and adverse reactions in the hospital.Conclusion The blood circulation punching apparatus is suitable for cerebrovascular and hypertension patients with stable blood pressure and normal cardiopulmonary function and can prevent thrombus of lower extremity veins effectively.

OBJECTIVETo prepare the gastric retenting and chronopharmacologic drug delivery tablets containing sinomenine hydrochloride as a model drug, evaluate the effects of the coating layers formulation and technics on drug release behavior, and to elucidate the mechanism of drug release based on obtained results.

METHODThe gastric retenting and chronopharmacologic drug delivery tablets were prepared by press-coated technics. The types of disintegrants were chosen according to the expanding rate and the lag-time. The effects of formulation and technics of coating layer on the release characteristic of the drug were investigated by dissolution testing. The mechanism of drug release was proved by erosion test.

RESULTThe tablets had typical chronopharmacologic drug delivery properties with a lag time followed by a rapid release phase. CMS-Na was selected as the disintegrant. The lag-time was prolonged with the increase of the ratio of HPMC/carrrageenan and the amount of matrix material in coating layer. The compressing pressure and preparation method of coat material had minor influence on the lag-time of the tablets. Coating layer erosion and tablet core swelling were involved in the mechanism of drug release.

CONCLUSIONThe tablets had typical chronopharmacologic drug delivery properties. A suitable lag-time can be achieved by adjusting formulation of coating layer to meet the requirement of chronotherapy.

Chemistry, Pharmaceutical ; Drug Chronotherapy ; Drug Delivery Systems ; methods ; Humans ; Morphinans ; chemistry ; pharmacokinetics ; Stomach ; drug effects ; Tablets, Enteric-Coated ; chemistry ; pharmacokinetics