OBJECTIVE: To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects. METHODS: The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively. RESULTS: NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05). CONCLUSION NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.
Rats ; Animals ; Osteogenesis ; Delayed-Action Preparations/pharmacology* ; Microspheres ; Berberine/pharmacology* ; Anti-Bacterial Agents/pharmacology* ; Escherichia coli

OBJECTIVETo compare the action of miosis of 1% pilocarpine liposome with 1% pilocarpine solution in rabbits.

METHODS18 white rabbits were randomly divided into 3 groups. Test group received 1% pilocarpine liposome, positive control group received 1% pilocarpine solution, negative control group received liposome. Each eye drop instilled into left eye of rabbits and sterile saline solution instilled into right eye as control. The pupil diameter was measured at time intervals of beginning, 0.25, 0.5, 1, 2, 3, 4, 5, 7 hours.

RESULTSThe mean pupil diameter change of 3 groups in both eyes was not significant (P > 0.05) at beginning. The strongest action of miosis took place 0.25 h in positive control group and 0.5 h in test group after instillation. The dilation of pupil in both groups took place 1 h and 3 h, and the restoration of pupil in both groups took place at 5 h and 7 h. The mean pupil diameter of negative control group was not significant in seven hours.

CONCLUSIONSThe results suggest that 1% pilocarpine liposome improves the bioavailability and prolong the duration of its action.

Animals ; Delayed-Action Preparations ; Female ; Liposomes ; pharmacology ; Male ; Miotics ; pharmacology ; Pilocarpine ; administration & dosage ; pharmacology ; Pupil ; drug effects ; Rabbits ; Random Allocation

OBJECTIVETo prepare a platinum microcoil coated with polymers and vascular endothelial growth factor (VEGF), and evaluate its surface characteristics and property of sustained VEGF release.

METHODSThe surface of the platinum microcoils (GDC) were modified by coating P(DLLA-co-TMC) copolymer and immobilizing heparin on the surface of GDC. VEGF was then loaded onto the surface of GDC and the controlled release of VEGF within GDC was achieved. The morphology was observed by scanning electron microscope, and the sustained release of VEGF was evaluated by enzyme-linked immunosorbent assay (ELISA).

RESULTSPlatinum coils were prepared by successive deposition of P(DLLA-co-TMC) copolymer and anionic heparin, and VEGF was immobilized through affinity interaction with heparin. The accumulative release of VEGF increased obviously during the entire testing period without burst release.

CONCLUSIONThe use of P(DLLA-co-TMC) copolymer allows immobilization of VEGF on the platinum coils for controlled VEGF release, and improves the biological property of the coils.

Coated Materials, Biocompatible ; chemistry ; Delayed-Action Preparations ; pharmacology ; Platinum ; chemistry ; Polymers ; chemistry ; Vascular Endothelial Growth Factor A ; pharmacology

OBJECTIVETo study the preparative method of controlled release microspheres incorporating basic fibroblast growth factor (bFGF) and the bioactivities of bFGF, which were released from bFGF microspheres, on the cultured Schwann cells.

METHODSbFGF was microcapsulated with the multiple emulsion encapsulative method using polylactic-co-glycolic acid (PLGA) as coating material. Its morphology, particle size distribution, drug loading, enveloping rate and in vitro release property were studied. The cultured Schwann cells were grouped according to the different ingredients being added to the culture medium of bFGF group or bFGF-PLGA group. Then the cytometry, cytoactivity detection and mitotic cycle analysis of Schwann cells were performed.

RESULTSThe morphology and the particle size distribution of the bFGF-PLGA microspheres were even and good. The drug loading and enveloping rate of microspheres were (27.18 x 10(-3))%+/-(0.51 x 10(-3))% and 66.43%+/-1.24%. The release property of microspheres in vitro was good and the overall release rate was 72.47% in 11 days. The in vitro cellular study showed that: at the first 2 days of plate culture, the cell number and viability of the bFGF group were statistically higher than the bFGF-PLGA group; at the 3rd and 4th days of plate culture, the cell number and viability of bFGF and bFGF-PLGA groups showed no difference; at the 6th and 8th days of the plate culture, the cell number and viability of the bFGF-PLGA group were statistically higher than the bFGF group. By flow cytometry examination, at the 2nd day of plate culture, the G2/M+S percentage of bFGF group was statistically higher than the bFGF-PLGA group, at the 4th and 8th days of plate culture, the G2/M+S percentage of the bFGF-PLGA group was statistically higher than the bFGF group.

CONCLUSIONSIt is practical to prepare the bFGF-PLGA microspheres with the multiple emulsion encapsulative method. bFGF-PLGA microspheres can preserve the bioactivities of bFGF effectively and promote the proliferation of Schwann cells in a long period because of the controlled release of bFGF from the microspheres.

Animals ; Delayed-Action Preparations ; Fibroblast Growth Factor 2 ; administration & dosage ; pharmacology ; In Vitro Techniques ; Microspheres ; Rabbits ; Schwann Cells

OBJECTIVETo prepare cisPLLAtin-loaded polylactic acid/cnts, and to study the anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines(MGC803 and MNK45).

METHODS5-FU-PLLA-CNTs were prepared with ultrasound emulsification. The morphology of 5-FU-PLLA-CNTs was determined by scanning electron microscope(SEM), and its drug loading and drug release curve in vitro were detected by UV-Vis-NIR spectrophotometer. Cells were divided into experiment, positive control and negative control groups. CCK8 method was used to test the cytotoxic effect of 5-FU-PLLA-CNTs in different concentrations on MGC803 and MNK45 cell proliferation. Flow cytometry was employed to measure the apoptotic rate of MGC803 and MNK45 cells before and after the intervention of 5-FU-PLLA-CNTs.

RESULTSDeep layer film of 5-FU-PLLA-CNTs was successfully established, whose drug-load rate was(4.54±0.43)%, entrapment rate was(21.56±2.36)%. In vitro release test showed release rate within 24 h of 5-FU-PLLA-CNTs was 23.9% in a as lowly increasing manner, and accumulating release rate was 85.3% at day 31. CCk8 experiment revealed, as compared to control group, 5-FU-PLLA-CNTs significantly inhibited the proliferation of two cell lines in dose-dependent and time-dependent manner. The best 5-FU-PLLA-CNTs concentration of inhibition for human gastric cancer cell lines was 1 mg/well. Flow cytometry indicated the apoptotic rate of MGC803 and MNK45 cells in experiment group treated by 1 mg/well 5-FU-PLLA-CNTs significantly increased as compared to negative control group (P<0.05), while the difference was not significant as compared to positive control group (P>0.05).

CONCLUSIONThe 5-FU-PLLA-CNTs has good drug sustained-release capacity, and can significantly kill and inhibit the proliferation of MGC803 and MNK45 cell lines.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Delayed-Action Preparations ; Fluorouracil ; pharmacology ; Humans ; Lactic Acid ; pharmacology ; Nanotubes, Carbon ; Polyesters ; Polymers ; pharmacology ; Stomach Neoplasms ; pathology

In this work a system which consists of chitosan (CS) microcores entrapped within enteric polymer is presented. Vitamin D2, used as a model drug, was efficiently entrapped within CS microcores using spray-drying and then microencapsulated into ethylic cellulose(EC). The morphology and release properties of microcapsules were tested. The influential factors of preparation conditions included molecular weight of chitosan, concentration of chitosan solution, concentration of acetic acid, loading of vitamin D2 were discussed. The results of in vitro release studies showed that the microcapsules prepared in this article could realize sustained release in intestine.
Capsules ; Cellulose ; analogs & derivatives ; pharmacology ; Chitin ; analogs & derivatives ; pharmacology ; Chitosan ; Delayed-Action Preparations ; Drug Compounding ; Drug Delivery Systems ; Ergocalciferols ; pharmacology ; In Vitro Techniques

This study was aimed to reveal how the swelling properties and release behavior of a model drug from pectin gel beads were influenced by its crosslinking with different metal ions. Coomassie Brilliant Blue G-250 was chosen as the model drug. Pectinate beads were prepared by the dropping method and crosslinked with Ca2+, Fe3+, Zn2+, Ba2+, respectively. The release behavior and swelling properties were investigated. The results showed that there were significant differences between the pectinate beads that were crosslinked with different ions. Pectinate gel beads, as a potential cell microencapsulation and drug vehicle, could be acquired for different release profile by crosslinking with different ions.
Calcium ; chemistry ; pharmacology ; Cross-Linking Reagents ; Delayed-Action Preparations ; Drug Carriers ; chemistry ; Ferric Compounds ; chemistry ; pharmacology ; Gels ; chemistry ; Metals ; chemistry ; pharmacology ; Microspheres ; Pectins ; chemistry

AIMTo study unitary-core osmotic pump tablet for delivering water-insoluble drug for 24 hours.

METHODSUnitary-core osmotic pump tablet was prepared using nifedipine as the model drug. The effects of various core formulation variables on drug release were studied.

RESULTSPolyethylene oxide and potassium chloride have comparable positive effects on drug release, whereas, nifedipine has markedly negative effect on drug release.

CONCLUSIONUnitary-core osmotic pump tablet is very easy in preparation and it can deliver water-insoluble drug in substantially constant rate for 24 hours.

Calcium Channel Blockers ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Delivery Systems ; Nifedipine ; administration & dosage ; chemistry ; Osmosis ; Polyethylene Glycols ; pharmacology ; Potassium Chloride ; pharmacology ; Solubility ; Tablets ; Technology, Pharmaceutical ; methods

AIMTo evaluate how solution viscosity affects the precorneal residence of five water-soluble polymers with different properties.

METHODSCaptive bubble technique was used, with the consecutive change of contact angle interpreted as an indication of desorption process, to study the residence of those polymers in vitro on freshly enucleated rabbit eyes under physiological conditions.

RESULTSCarbopol and sodium hyaluronate (HA), which adsorbed to isolated ocular surface more than 15 min, showed the optimum precorneal retentive capabilities. When the solution viscosity increased from 12 mPa.s to 50 mPa.s, the residence time of carbopol and HA were prolonged 10 min and 7 min, respectively, but that of sodium carboxymethylcellulose was not affected.

CONCLUSIONThe result suggested that higher viscosity is beneficial to improve the ocular residence time of bio-adhesive polymers.

Acrylic Resins ; Adhesiveness ; Animals ; Cornea ; drug effects ; metabolism ; Delayed-Action Preparations ; Drug Carriers ; Female ; Hyaluronic Acid ; pharmacokinetics ; pharmacology ; In Vitro Techniques ; Male ; Polyvinyls ; pharmacokinetics ; pharmacology ; Rabbits ; Solutions ; Viscosity

AIMTo prepare bioadhesive microspheres of metronidazole (Metro) with prolonging resident time in the stomach and sustaining drug release.

METHODSThe microspheres were prepared by a drying-in-liquid method. The appearance, particle size and drug release in vitro were examined. The factors influencing bioadhesive property and drug release, such as ethyl cellulose (EC)/carbopol 934P (CP) ratio, particle size and Metro content were investigated.

RESULTSThe average diameter of the Metro-EC-CP microspheres was 559.9 microns. The release profiles of metronidazole were shown to fit to first-order equations well. With the increase of CP content in the Metro-EC-CP microspheres, the microspheres showed better mucoadhesion and faster drug release. The drug release rate decreased with the increase of particle size and the decrease of Metro content.

CONCLUSIONThe Metro-EC-CP microspheres have a sound mucoadhsive property and sustained drug release when the ratio of EC and CP was 17:3 and Metro content was 25%. The drug release was shown to last for 8 h in 0.1 mol.L-1 hydrochloric acid.

Acrylates ; Animals ; Anti-Infective Agents ; administration & dosage ; pharmacology ; Cell Adhesion ; Delayed-Action Preparations ; Female ; Fluorocarbons ; chemistry ; Gastric Mucosa ; physiology ; Metronidazole ; administration & dosage ; pharmacology ; Microspheres ; Rats ; Rats, Sprague-Dawley