Preparation and evaluation of ophthalmic thermosensitive in situ gels of penciclovir

Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 （12%） showed potential for use as a drug delivery system with improved ocular bioavailability.

A stepwise optimization strategy to formulate in situ gelling formulations comprising fluconazole-hydroxypropyl-beta-cyclodextrin complex loaded niosomal vesicles and Eudragit nanoparticles for enhanced antifungal activity and prolonged ocular delivery

Fungal keratitis and endopthalmitis are serious eye diseases.Fluconazole(FL)is indicated for their treatment,but suffers from poor topical ocular availability.This study was intended to improve and prolong its ocular availability.FL niosomal vesicles were prepared using span 60.Also,polymeric nanoparticles were prepared using cationic Eudragit RS100 and Eudragit RL100.The investigated particles had adequate entrapment efficiency(EE%),nanoscale particle size and high zeta potential.Subsequently,formulations were optimized using full factorial design.FL-HP-β-CD complex was encapsulated in selected Eudragit nanoprticles(FL-CD-ERS1)and niosmal vesicles.The niosomes were further coated with cationic and bioadhesive chitosan(FL-CD-Nios-ch).EE%for FL-CD-ERS1 and FL-CD-Niosch formulations were 76.4%and 61.7%;particle sizes were 151.1 and 392 nm;also,they exhibited satisfactory zeta potential+40.1 and+28.5 m V.In situ gels were prepared by poloxamer P407,HPMC and chitosan and evaluated for gelling capacity,rheological behavior and gelling temperature.To increase the precorneal residence time,free drug and selected nano-formulations were incorporated in the selected in situ gel.Release study revealed sustained release within 24 h.Permeation through excised rabbits corneas demonstrated enhanced drug flux and large AUC0-6 h in comparison to plain drug.Corneal permeation of selected formulations labeled with Rhodamine B was visualized by Confocal laser microscopy.Histopathological study and in vivo tolerance test evidenced safety.In vivo susceptibility test using Candida albicans depicted enhanced growth inhibition and sustained effect.In this study the adopted stepwise optimization strategy combined cylodextrin complexation,drug nano-encapsulation and loading within thermosenstive in situ gel.Finally,the developed innovated formulations displayed boosted corneal permeation,enhanced antifungal activity and prolonged action.

Study on Rheology and Release Kinetics of Chuanqi Ophthalmic Microemulsion in situ Gel

[Objectives] To study the rheology and release kinetics of Chuanqi ophthalmic microemulsion in situ gel,so as to provide references for its future study and development. [Methods]The fluid properties and linear viscoelastic regions of this preparation were investigated by MCR 102 rheometer. The release kinetics of Chuanqi ophthalmic microemulsion in situ gel was evaluated by modified Franz diffusion cell method,the ligustrazine and ligustilide were selected as the indictors,and semi-permeable membrane was used as a barrier,sampling time point was 0. 5,1,2,4,6,and 8 h respectively. [Results]Chuanqi ophthalmic microemulsion in situ gel was a pseudoplastic fluid and it had a linear viscoelastic region. Taking the shear stress as the indicator,the linear viscoelastic region was 0-302. 74 Pa; taking the strain as the indicator,the linear viscoelastic region was 0-7. 45%. At the critical point,the storage modulus( G') = the loss modulus( G″) =2 976. 60 Pa,critical shear stress was 302. 74 Pa and critical strain was 7. 45%. The average cumulative release of ligustrazine of 6 samples within 8 h was 33. 71 μg,the average cumulative release rate reached 90. 08%,and the release kinetics followed Higuchi equation. The average cumulative release of ligustilide of 6 samples within 8 h was 68. 46 μg,the average cumulative release rate reached 84. 32%,and the release kinetics followed the zero-order kinetics equation. [Conclusions] Chuanqi ophthalmic microemulsion in situ gel has excellent viscoelasticity and its strain is reversible in a certain range. The release kinetics of ligustrazine is the result from synergistic effect of its physicochemical properties and matrix skeleton,while the release kinetics of ligustilide is mainly affected by its physicochemical properties.

Doxorubicin-loaded zein in situ gel for interstitial chemotherapy of colorectal cancer

The aim of this research was to evaluate doxorubicin(DOX)-loaded zein in situ gels,a new drug delivery system in which a liquid state drug can be transformed into semi-solid after intratumoral injection.In vitro release of DOX-loaded zein was investigated and the pharmacokinetics,biodistribution and therapeutic efficacy of these DOX-loaded zein formulations were investigated using BAI B/c nude tumor-bearing mice.In vitro release of DOX from the gels extended up to 7 days.Efficient accumulation of DOX in the tumor with lower drug concentration in blood and normal organs was obtained resulting in effective inhibition of tumor growth and fewer off-target side effects.In conclusion,a DOX-loaded in situ gel was developed with sustained release,enhanced anti-cancer efficacy for colorectal cancer in vivo,and especially with reduced off-target side effects.

Effect of peritumoral injection of boanmycin hydrochloride within temperature-sensitive in situ gel using Hep-G2 hepatoma nude mice model

Background Boanmycin hydrochloride, a new antitumor agent, has a short half-life and fast clearance speed in vivo. The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model. Methods Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups： normal saline group, in situ gel only group, boanmycin hydrochloride in situ saline group, and boanmycin hydrochloride in situ gel group, and were treated with injection of corresponding agents into peripheral tissue of the tumor. The volume of the tumor and the body weight of the mice were regularly measured, and tumor growth curve was generated. The size, internal echo, and blood flow of the tumors were observed by color Doppler ultrasonography. Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy. Results The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%. The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound. Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however, there was massive calcification and no blood flow in the tumor in the boanmycin hydrochlodde in situ gel group. Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group. Conclusion Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

Flexible lithium metal capacitors enabled by an in situ prepared gel polymer electrolyte

The rapid development of next-generation flexible electronics stimulates the growing demand for flexible and wearable power sources with high energy density.Li metal capacitor(LMC),combining with a Li metal anode and an activated carbon cathode,exhibits extremely high energy density and high power density due to the unique energy storage mechanism,thus showing great potential for powering wearable electronic devices.Herein,a flexible LMC based on an in situ prepared PETEA-based gel polymer electrolyte(GPE)was reported for the first time.Owing to the high ionic conductivity of PETEA-based GPE(5.75×10^(−3)S/cm at 20℃),the assembled flexible LMC delivers a high capacitance of 210 F/g at 0.1 A/g within the voltage range from 1.5 V to 4.3 V vs.Li/Li^(+),a high energy density of 474 Wh/kg at 0.1 A/g and a high power density of 29 kW/kg at 10 A/g.More importantly,PETEA-based GPE endows the LMC with excellent flexibility and safety,which could work normally under abuse tests,such as bending,nail penetration and cutting.The in situ prepared PETEA-based GPE simplifies the fabrication process,avoids the risk of leakage and inhibits the growth of Li dendrite,making LMC a promising flexible energy storage device for the flexible electronic field.