An experimental study on the biological characteristics of SDF-1/CS/β-GP composite bio-membrane in vitro / 口腔医学

Objective@#To prepare a composite membrane by chitosan/β-sodium glycerophosphate(CS/β-GP) thermosensitive hydrogel combined with stromal cell derived factor-1(SDF-1) and observe its biological characteristics in vitro.@*Methods@#Different doses of SDF-1 were added into CS/β-GP solution and then the thermosensitive gel time was measured. The SDF-1/CS/β-GP solution was membrane paved and dried to prepare composite membranes. The morphological characteristics were observed by scanning electron microscope(SEM). Composite membranes were placed into cell culture medium, and the supernatant(n=3) was extracted after standing at 6, 12, 24, 36, 48, 60 h, respectively. The concentration of SDF-1 in the solution was measured. Bone mesenchymal stem cells(BMSCs) were cultured in the Transwell room, and the composite membranes containing different concentrations of SDF-1 were placed in the lower chamber. There were four groups(n=3): Group M0 used CS/β-GP membrane(control group), Group M1, M2, M3 used SDF-1/CS/β-GP membrane(SDF-1 was 100, 200, 400 ng/mL respectively). After culture for 6, 12 and 24 h, the cells under the membrane were preserved and Giemsa stained and counted. The absorbance(OD) value was measured by MTT method to calculate the cell proliferation rate. SPSS 19.0 was used for multi-factor analysis of variance.@*Results @#After adding a certain amount of SDF-1 into CS/β-GP solution, the gel time did not change significantly(P>0.05). The SDF-1/CS/β-GP membrane was translucent and porous at 37 ℃. In this experiment, the volumic mass of SDF-1 released by SDF-1/CS/β-GP composite membrane increased gradually with the experimental time(P<0.01). Transwell cell chemotaxis test showed that the number of BMSCs cells with directional migration increased with the prolongation of observation time(P<0.01) and the increase of SDF-1 volumic mass(P<0.01). In MTT test, the OD value of migration cell solution increased with the prolongation of time(P<0.01) and the increase of SDF-1 volumic mass(P<0.01). @*Conclusion@# The SDF-1/CS/β-GP composite membrane has a porous structure and biological activity of chemotactic BMSCs directional migration. It is a potential membrane for guided tissue regeneration.

Preparation, in vitro characterization and pharmacokinetics of paclitaxel thermosensitive gel / 药学学报

Local drug delivery is a new strategy to prevent postoperative recurrence of cancer, thermosensitive gel is a typical topical drug delivery system. In this study, a novel paclitaxel thermosensitive gel (PTG) was prepared to prevent recurrence after chemotherapy for cancer, the effects of drug particle size on release and absorption rate in vivo were investigated. Paclitaxel suspensions with different particle sizes were prepared by medium grinding, high pressure homogenization, air crushing and screening. Using poloxamer as the gel matrix and carbomer as the biological adhesive, Box-Behnen was used to optimize the formulation of PTG. The morphology, viscosity, rheological properties and biological adhesion of thermosensitive gel were characterized. The relationship between dissolution and release of thermosensitive gel was investigated by weight loss method, pharmacokinetics was studied in rats. The paclitaxel suspensions with the particle sizes of 350 nm, 800 nm, 3 μm and 9 μm were prepared, 19% poloxamer 407, 4% poloxamer 188 and 0.1% carbomer were used to prepare PTG. The phase transition temperature of thermosensitive gel was 30 to 35 ℃, there was a good linear relationship between in vitro release and gel dissolution. In the pharmacokinetic study, area under the curve (AUC0-t) increased with the decrease of particle size. In general, the PTG prepared in this study can rapidly change into gel under human body temperature, provided with good adhesion. The release rate in vitro is closely related to the particle size, the release rate increased with the decrease of particle size. This study provides data support for preventing postoperative recurrence of cancer. The animal welfare and experimental process in this paper follow the regulations of the Animal Ethics Committee of the Academy of Military Medical Sciences.

Based on clinical application research progress of thermosensitive gel in different drug delivery sites / 药学学报

The advantages of local administration are as follow: release drugs directly at the lesion, increase the drug concentration in lesion location and reduce the side effects of systemic administration. Thermosensitive gel is one of typical local administration agents. It exhibits the different physical characteristics with the change of temperature. It is sol-gel at low temperature or storage temperature, while when the temperature rises to the transition temperature or near the body temperature, it is semisolid gel with a certain viscoelasticity, and can recover rapidly. It can enhance the local adhesion, which prolongs the local retention time of drugs. As a result, thermosensitive gel can control and display the release of drugs, which can significantly improve the bioavailability of drugs. This review summarizes the characteristics of thermosensitive gel, thermosensitive materials, and its application in different parts: nasal cavity, eye, vagina, periodontal, skin, tumor and joint cavity, based on clinical needs.

Preparation and in vivo and in vitro Characteristic Evaluation of Ligustrazine Ophthalmic Liposome Thermosen- sitive Gel / 中国药房

OBJECTIVE：To prepare Liguatrazine opthalmic liposome therm osensitive gel ，and to investigate its in vivo and in vitro characteristics. METHODS ：The ammonium sulfate gradient method was used to prepare Liguatrazine liposomes. The preparation technology was optimized by using orthogonal test. Using poloxamer P 407 as gel matrix ，Liguatrazine liposomes were prepared into thermosensitive gel. A membraneless model was used to study the dissolution and in vitro drug release of the gel. The modified Franz diffusion cell was used to investigate corneal permeability and further determine corneal hydration value. The effects of the gel on the proliferation of human corneal epithelial cell HCE-T. HE staining and Draize test were used to investigate the stimulatory effects of the gel on corneal cells of the rabbit ，and the histological changes of the eyes were observed. RESULTS ：The optimal preparation technology of Liguatrazine liposome was drug-lipid ratio of 1 ∶ 10（m/m），the ammonium sulfate concentration of 0.2 mol/L，phospholipid-cholesterol ratio of 4∶1（m/m），incubation temperature of 45 ℃. Then ligustrazine opthalmic liposome thermosensitive gel was prepared with 23％ poloxamer P 407 as gel matrix. The gel had good gelatinization temperature. The in vitro drug release and dissolution showed zero-order kinetic characteristics ，and in vitro drug release of the gel was mainly related to dissolution （R2＝0.993 4）. The cumulative transcorneal permeability of the gel was 43.3％ within 6 hours and corneal hydration value was 72.98％. Low and medium concentrations （1，5 mg/L）of Ligustrazine opthalmic liposome thermosensitive gel had no obvious proliferation toxicity to HCE-T cells ，but it showed cytotoxicity at high concentration （10 mg/L）. The mean Draize eyeirritation score of the gel on rabbit cornea was within non-stimulation，and there was no abnormal change in rabbit （No.2018001） corneal histology. CONCLUSIONS ： Prepared Ligustrazine opthalmic liposome thermosensitive gel has a suitable phase transition temperature ，good corneal permeability ，and low corneal irrit ation.

Thermosensitive In Situ Gel Of Tinidazole In Treatment Of Bacterial Vaginosis: Formulation And Evaluation

Bacterial Vaginosis (BV) is the leading cause of vaginal discharge. Because of its big surface area, wealthy blood supply, avoidance of the first-pass effect and high permeability to many drugs, the vagina offers a promising location for local impact as well as systemic drug delivery. In situ gels give several benefits, such as ease of administration in the respective body cavities, elevated spreadability at certain temperatures, reduced administration frequency, improved patient compliance and comfort compared to standard dosage forms. Tinidazole (TNZ) can give effective treatment over the BV. In situ gel of TNZ containing polaxomer 407and HPMC E100 or carbopol 941NF was optimized on the basis of various evaluation parameters. Gelation temperature (Tgel) and pH of all batches was found in range of 36.6 to38.0 ºC and 4.20 to 5.03, viscosity was found in range of 1100-2050 cps at 25ºC and 4800-6530 cps at 37ºC. The Spredability was found in range of 16-20 cm. From these evaluation parameters we selected best combination for the mucoadhesive property, antimicrobial study, in vitro drug release and for HET CAM irritation study. The optimized formulation gives satisfactory results. In this study we also compare the performance of two mucoadhesive polymer. Based on maximum desirability and cost effectiveness, in situ vaginal gel containing 20% polaxomer and 0.5% HPMC E100 could be considered as a highly promising treatment for bacterial vaginosis.

Thermosensitive gel of polysaccharide from Ganoderma applanatum combined with paclitaxel for mice with 4T1 breast cancer / 中国中药杂志

Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function. There were no reports on antitumor effect of its intratumoral injection. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after removing protein by Sevage method. The total polysaccharide content from G. applanatum(PGA)was about 63%. The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro. In addition, the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually. The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407. The gel temperature was 36 ℃, and the PGA-TG could effectively slow down the release rate of PGA in vitro. 4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX). In high and low dose PGA groups, each mice was given with 2.25, 1.125 mg PGA respectively, twice in total, and the dosage of paclitaxel was 15 mg·kg~(-1), once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in low dose PGA-TG combined with nab-PTX group, and 68.10% in high dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05). The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.

Preparation of Periplaneta americana Thermosensitive Hydrogel and Investigation of Its Wound Healing Effect on Diabetic Rats / 中国实验方剂学杂志

Objective:To prepare Periplaneta americana thermosensitive hydrogel and investigate its effect on wound healing in diabetic rats. Method:Taking N-isopropylacrylamide (NIPAM) and acrylic acid (AAc) as monomers, thermosensitive poly(NIPAM-co-AAc) [P(NIPAM-co-AAc)] polymeric material was prepared by free radical polymerization, then thermoresponsive copolymer P(NIPAM-co-AAc)-g-HA was synthesized by conjugating P(NIPAM-co-AAc) to hyaluronic acid (HA). The structure and lower critical solution temperature (LCST) of the graft copolymer were characterized by proton nuclear magnetic resonance spectroscopy (1H-NMR) and ultraviolet spectrophotometry (UV). P. americana thermosensitive hydrogel was prepared by dialysis method, and it was characterized by scanning electron microscope (SEM), rotation rheometer and thermogravimetric analyzer to observe section structure, rheological properties and thermal stability. Differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy were employed to identify the inclusion of P(NIPAM-co-AAc)-g-HA temperature sensitive material for P. americana extract, and to investigate the effect of P. americana thermosensitive hydrogel on wound healing in diabetic rats, and the rate of wound healing was calculated by Image-Pro Plus 6.0 software. Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes of the wounds of rats in each group. Result:P(NIPAM-co-AAc)-g-HA temperature sensitive material was successfully synthesized, its LCST was between 29 ℃ and 31 ℃, it had a dense and uniform porous structure and could uniformly include P. americana extract. Pharmacodynamic studies showed that P. americana thermosensitive hydrogel group had the best effect on promoting wound healing, its infiltration degree of inflammatory cells was significantly reduced, collagen and fibroblasts arranged neatly and compactly, and the density of neovascularization was significantly increased by comparing with the model group. Conclusion:P. americana thermosensitive hydrogel can effectively promote wound healing of diabetic rats and overcome the shortage of marketed P. americana liquid preparations, this paper can provide a reference for the development of P. americana extract preparations to promote wound healing in diabetic patients.

Optimization of Paeonol NLC Thermosensitive Gel Formulation by Box-Behnken Response Surface Methodology / 中国中医药信息杂志

Objective To optimize the formulation of paeonol nanostructured lipid carrier (NLC) thermosensitive in situ gel through Box-Behnken response surface method; To investigate its release properties in vitro to provide references for the study of transdermal drug delivery system. Methods Taking mass fraction of poloxamer 407 and poloxamer 188 as the factors, the gelling temperature as the index, the mathematical relationship between the gelling temperature and two factors was established by binomial model and multivariate linear regression model. The Box-Behnken response surface method was used to optimize the formulation of paeonol NLC thermosensitive in situ gel, and the in vitro release characteristics of the preparation was investigated. Results There was a credible quantitative relationship between the gelling temperature and the 2 factors, and the binomial model was more reliable than the multivariate linear model. The best prescriptions of paeonol NLC thermosensitive in situ gel were 22.90% poloxamer 407 and 3.34% poloxamer 188; gelling temperature was (33.4±0.1)℃, and the cumulative release amount of paeonol in situ gel in 24 h was 51.19%. Conclusion This method is suitable for the formulation optimization of paeonol NLC thermosensitive in-situ gel, and the established mathematical model has good predictability. The optimized formulation can provide references for the development of paeonol transdermal preparation.

Preparation and in vitro Drug Release of Ocular Thermosensitive Gel of Atropine Sulfate / 中国药师

Objective:To prepare the ocular thermosensitive gel of atropine sulfate and study its in vitro release. Methods: The gel formula was optimized by central composite design response surface methodology. The influences of the amounts of poloxamer 407 (P407) and poloxamer 188(P188) on gelling temperature before and after the dilution with simulated tear fluid were investigated. A membraneless dissolution model was used to determine the gel erosion and in vitro release. Results:The optimized gel formula was as follows:23% P407 and 5% P188. The deviations between the measured values and predicted values were all lower than 5%. The in vitro release experiment showed that the gel erosion and the drug release fitted zero-order kinetics equations with promising correlation, indicating a dissolution-controlled release mechanism. Conclusion:The optimization of the ocular thermosensitive gel of atropine sul-fate can be achieved by central composite design response surface methodology with good estimation. The thermosensitive gel with sus-tained drug release property meets the design requirements.

Preparation of triptolide nano liposome thermosensitive gel and its penetrability through nasal mucosa / 中草药

Objective To prepare nasal triptolide nano liposome thermosensitive gel (TP-NLS-TG) and investigate the in vitro penetrability through nasal mucosa. Methods The triptolide nanoliposomes were prepared by high pressure homogenization method, and the ratio of poloxamer 407 (P-407) and poloxamer 188 (P-188) was selected, using the azone dosage and stirring time as investigation factors. Gelation temperature (GT) and homogeneity of TG (RSD) were used as evaluation indexes, and TP-NLS-TG was prepared by optimized prescription. An isolated mucosal permeability model was established by frog abdominal skin to carry out the in vitro permeation test of TP-NLS-TG in nasal mucosa. Results The best prescription was 12% P-407, 10% P-188, and 3% azone, and swelling time was 4 h. The TP-SLN gelation temperature of the gel was 32 ℃, and the RSD was 0.005%. In the first 8 h, the cumulative infiltration volume per unit area was (9.296 3 ± 0.614 7) μg/cm2, and the release curve in line with the Higuchi mathematical model. Conclusion The triptolide nano liposome gel prepared by the optimum technology has an accurate gelling temperature, and uniform content, which has good permeability, can be absorbed through the frog skin.

Preparation and in Vitro Properties of Paeonol Thermo Sensitive Gel / 世界科学技术-中医药现代化

This study aimed at preparing paeonol thermosensitive gel and preliminary exploring its properties in vitro.Tube inversion method was adopted to investigate the effects of concentrations of poloxamer 407 and poloxamer 188 on gelation temperature.Then,viscosity of the gel was detected by rotary viscometer,and in vitro erosion and drug release characteristics of the gel by no film stripping method.As a result,the gelation temperature of poloxamer 407 decreased with the increase of its concentration,while gelation temperature of poloxamer 407 increased with the accelerating concentration of poloxamer 188.The cumulative drug release of paeonol thermo sensitive gel was up to 70％ in 320 rin.Gel dissolution and drug release were simultaneously performed without burst release phenomenon.It was concluded that the preparation process of paeonol thermo sensitive gel was simple and easy to use with the overt effect of sustained-release.

Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues / Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues

ABSTRACT Drug delivery to treat ocular disorders locally is a challenging endeavor. Traditional ocular dosage form - eye drops - exhibits poor availability, consequently inefficient therapeutic response. The objective of the study was to formulate and characterize a ketorolac tromethamine ocular system with a prolonged release pattern based on liposomes as a vesicular carrier and to design once daily liquid preparation realizing the thermal in situ gelation principle. Liposomes were prepared by film hydration method. The influence of cholesterol concentration, pH and volume of hydration medium, and type and concentration of charging imparting agents were studied. Liposomes were characterized via, morphological examination, vesicular size, and encapsulation efficiency, and in vitro release performance, moreover its stability was assessed. The results obtained highlighted that liposomes showed a closed vesicular multi-lamellar structure. Ketorolac was successfully encapsulated within the liposomal structure in a cholesterol and charge inducing agent concentration-dependent behaviour. The dispersion of liposomes within thermosensitive Poloxamer in situ gel was able to retard the release of the drug by diffusion providing a controlled prolonged delivery. The liposomal formulations were physically stable for six months. Ketorolac tromethamine in situ liposomal gel representing an efficient alternative in terms of ocular retention and patient compliance when compared with conventional eye drops.

Evaluation of in Vitro Release Profile and Local Retention of Estradiol Vaginal Thermosensitive Gel / 中国药学杂志

OBJECTIVE: To examine the in vitro release profile and in vivo retention of estradiol vaginal thermosensitive gel (E2-VTG). METHODS: E2-VTISG was prepared by cold dissolving method.The dynamic membrane dialysis method and HPLC-fluorometric method were used to determine the in vitro release characteristic of the estradiol vaginal thermosensitive gel.CRi Maestro was applied to evaluate the retention of E2-VTG in ICR mice with IR820 as the fluorescent marker. RESULTS: Estradiol could be released slowly from the thermosensitive gel and the release profile was fitted with Higuchi equation. It was speculated that estradiol was mainly released through diffusion.NIR imaging and fluorescence quantitative analysis showed that thermosensitive gel could reside in vagina for at least 8 h. CONCLUSION: Estradiol thermosensitive gel can prolong the drug residence time in vagina and sustain the drug release rate.

Formula Optimization and Quality Control of Amlexanox Nasal Thermosensitive Gel Spray / 中国药师

Objective:To optimize the formula of amlexanox nasal thermosensitive gel spray and establish the quality control meth-od. Methods:Amlexanox nasal thermosensitive gel spray was prepared by a cold dissolving method, and poloxamer 407 (P407) and poloxamer 188 (P188) were used as the carrier materials. Central composite design-response surface methodology was used to optimize the formula with the amount of P407 and P188 as the influencing factors and the gel temperature and the viscosity before gelling as the indices. The content of amlexanox was determined by HPLC. According to Chinese Pharmacopoeia (2010 edition), the other indices of the preparation such as appearance, pH, viscosity, content, total spray times of each bottle and the content of each spray were deter-mined as well. Results:The optimum ratio of P407 and P188 was 17. 0% and 0. 9%,respectively . The average recovery of amlexanox was 98. 8% and RSD was 1. 7%(n=9). The quality of 3 batches of amlexanox nasal thermosensitive gel spray met the related require-ments. Conclusion:The formula and preparation process of amlexanox nasal thermosensitive gel spray are reasonable and feasible with controllable quality, which is worthy of further research.

Gemcitabine hydrochloride thermosensitive gel injection preparation and contents determination / 药学实践杂志

Objective To prepare gemcitabine hydrochloride thermosensitive gel injection and to stablish the determina‐tion methods of its contents .Methods Gemcitabine hydrochloride thermosensitive gel injection was prepared using PLGA‐PEG‐PLGA as thermosensitive viecle .The contents of gemcitabine hydrochloride were determined by HPLC .Results The formulation contained 40 mg/ml gemcitabine and 20% (wt) PLGA‐PEG‐PLGA with phase‐transition temperature of (37 ± 0 .15) ℃ ,showing the best viscosity around human body temperature .Gemcitabine hydrochloride presented a good linearity in the range of 5‐500 μg/ml(r=0 .999 8) ,which had good precision and reproducibility .The recovery rate of low ,middle and high concentrations of gemcitabine hydrochloride were (99 .5 ± 3 .2)% ,(100 .4 ± 2 .4)% ,(102 .1 ± 2 .4)% ,n=3 ,respectively . The average contents of gemcitabine hydrochloride in three batches of sample were (101 .87 ± 2 .95)% ,(99 .4 ± 2 .73)% , (98 .98 ± 0 .71)% ,n=3 ,respectively .Conclusion The quality of gemcitabine hydrochloride thermosensitive gel injection with PLGA‐PEG‐PLGA as matrix could be controlled .It is a promising new drug for pancreatic cancer .

Optimization for Preparation Technology ofCangai Volatile Oil Dextrin Inclusion Compound/in situ Nasal Thermosensitive Gel by Central Composite Design-response Surface Method / 中国中医药信息杂志

Objective To optimize the preparation technology ofCangai volatile oil dextrin inclusion compound/ in situ nasal thermosensitive gel by the central composite design-response surface method.Methods In the design, the investigation factors were the amounts of poloxamer 407 and poloxamer 188, and the evaluation index was the gel temperature. Quadratic models were used to evaluate the mathematic relation between the evaluation index and two investigation indexes to identify the optimum prescription, and then the optimum prescription was verified. Results According to the quadratic models, it was found that there was reliable quantitative relation between the evaluation index and two investigation indexes, among which the optimum dosage was 19.37% for poloxamer 407 and 2.73% for poloxamer 188.Conclusion The optimum model ofCangai volatile oil dextrin inclusion compound/ nasal thermosensitive gel can be obtained from central composite design-response surface method based on quadratic models. This method is reliable and feasible, which can realize the prescription optimization of the in situ gel.

Preparation and properties of nepeta oil-oxymatrine lipidosome pro vagina thermosensitive gel / 中草药

Objective: To prepare the nepeta oil-oxymatrine (OMT) lipidosome pro vagina thermosensitive gel, and to investigate its in vitro drug release behavior. Methods: P-407 and P-188 were used as gel matrix to prepare the gel, and gelatinization temperature was applied as a target to optimize the prescription. The OMT lipidosome was prepared based on the multiple emulsion method, and the nepeta oil-OMT lipidosome pro vagina thermosensitive gel was obtained by cold-dissolving method. The content of OMT was determined by HPLC, and in vitro release properties of nepeta oil-OMT lipidosome thermosensitive in situ gel was investigated by dialysis method. Results: After optimization, the gel prescription was finally confirmed as 18% P-407, 5% P-188, and 0.2% hydroxy-propyl methyl cellulose (HPMC). The gelatination temperature for nepeta oil-OMT lipidosome thermosensitive gel was (36.8 ± 0.2)°C, and the in vitro accumulating release ratio of sinomenine in the nepeta oil-OMT lipidosome gel system was (58.89 ± 0.34)% and (66.38 ± 0.12)% after 48 h. Conclusion: The prepared nepeta oil-OMT lipidosome thermosensitive gel has the temperature sensitivity and sustained release effect, can effectively delay the release of the drug in vagina and improve the residence time in the vagina.

Preparation of ophthalmic thermosensitive in situ gel of moxifloxacin hydrochloride and its release be¬havior in vitro / 中国药学杂志

CONCLUSION: Uniform design method should be used to optimize the formulation of MH loaded ophthalmic thermosensitive gel. The optimized formulation containing 230 mg·mL-1 P407 and 80 mg·mL-1 PI88 covered the ophthalmic temperature, which can serve as a potential candidate for ophthalmic application.

Preparation of sinomenine hydrochloride nanoparticle thermosensitive gel for intra-articular injection and its characteristic investigation / 中草药

Objective: To prepare the solid lipid nanoparticle (SLN) thermosensitive gel of sinomenine hydrochloride (SH) for intra-articular injection and to investigate its in vitro drug release behavior. Methods: Poloxamer 407 (P-407) and Poloxamer 188 (P-188) were used as gel matrix to prepare the gel, and the gelatinization temperature was applied as a target to optimize the prescription. The SH-SLN was prepared based on the microemulsion technique, and the gel system containing SH-SLN was obtained by cold-dissolving methods. The content of SH was determined by HPLC, in vitro release characteristics of SH-SLN thermosensitive gel were investigated by dialysis method. Results: The optimal gel prescription was finally confirmed as 18% P-407, 5% P-188, and 0.6% HPMC. The gelatination temperature for SH-SLN thermosensitive gel was (34.5 ± 0.2)°C, and the in vitro accumulated release rates of SH in the SLN thermosensitive gel system were (57.79 ± 0.36)% after 24 h and (75.16 ± 0.12)% after 48 h. Conclusion: The SH-SLN thermosensitive gel has the temperature sensitivity and obvious sustained-release effect. The combination of nanoparticle thermosensitive gel will be used as a new drug delivery for intra-articular injection.

Preparation of Levofloxacin Thermosensitive Ocular Gel and Study on Drug Release in Vitro / 中国药房

OBJECTIVE:To prepare the levofloxacin(LEF)thermosensitive gel for ophthalmic drug delivery,and to study the drug release in vitro.METHODS:Poloxamer407was used as themosensitive material for the LEF eye drop,the best con?centration of poloxamer in prescription was selected according to the temperature of gel,a novel membraneless model was used to study the drug release.RESUTS:The detected concentration of LEF was in the linear range of3～11?g/ml(r=0.9991,n=6),the recovery was99.62%;The best concentration of poloxamer in prescription was18%;Drug release followed zero-order kinetics,and the quantity of drug release was controlled by that of gel dissolution.CONCLUSION:The preparation is simple in method and easy to control in dosage,therefore it shows a promising future in development.