ABSTRACT
PURPOSE: To prepare the levocarnitine thermosensitive in situ gel (LCTG) and evaluate its effect on dry eye disease (DED). METHODS: Draize eye irritation test and other examinations were used to evaluate the eye irritation after multiple administration of LCTG. The Schirmer test, fluorescein sodium staining, HE staining and TUNEL staining were used to detect the tear secretion, corneal injury, histopathological changes of the cornea and lacrimal gland, and the apoptosis rate of cornea epithelial cells after 3 days of the administration. The conjunctival goblet cell density was detected by PAS staining, and the expression levels of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) of corneal epithelial cells were detected by immunofluorescence staining after 7 days of the administration. RESULTS: LCTG is non-irritating to rabbit eyes and has good biocompatibility. LCTG administration for 3 days can significantly increase the amount of tear secretion in mice with DED, promote corneal epithelial integrity and central corneal epithelium thickness recovery, and improve the pathological morphology and structure of corneal and lacrimal gland tissues, and reduce the apoptosis rate of the corneal epithelial cells. After 7 days of the administration, the preparation can promote the proliferation of conjunctival goblet cells and down-regulate the cornea expression levels of MMP-3 and MMP-9 in epithelial cells. CONCLUSION: The LCTG has a good curative effect on mice with DED, and the overall curative effect is better than that of levocarnitine solution.
Subject(s)
Carnitine/administration & dosage , Cornea/metabolism , Drug Delivery Systems , Dry Eye Syndromes/drug therapy , Administration, Ophthalmic , Animals , Carnitine/pharmacology , Carnitine/toxicity , Disease Models, Animal , Epithelium, Corneal/drug effects , Epithelium, Corneal/metabolism , Female , Gene Expression Regulation/drug effects , Goblet Cells/drug effects , Goblet Cells/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/genetics , Mice , Mice, Inbred BALB C , Rabbits , Temperature , Treatment OutcomeABSTRACT
Curcumin (Cur) is a naturally hydrophobic polyphenol with potential pharmacological properties. However, the poor aqueous solubility and low bioavailability of curcumin limits its ocular administration. Thus, the aim of this study was to prepare a mixed micelle in situ gelling system of curcumin (Cur-MM-ISG) for ophthalmic drug delivery. The curcumin mixed micelles (Cur-MMs) were prepared via the solvent evaporation method, after which they were incorporated into gellan gum gels. Characterization tests showed that Cur-MMs were small in size and spherical in shape, with a low critical micelle concentration. Compared with free curcumin, Cur-MMs improved the solubility and stability of curcumin significantly. The ex vivo penetration study revealed that Cur-MMs could penetrate the rabbit cornea more efficiently than the free curcumin. After dispersing the micelles in the gellan gum solution at a ratio of 1:1 (v/v), a transparent Cur-MM-ISG with the characteristics of a pseudoplastic fluid was formed. No obvious irritations were observed in the rabbit eyes after ocular instillation of Cur-MM-ISG. Moreover, Cur-MM-ISG showed a longer retention time on the corneal surface when compared to Cur-MMs using the fluorescein sodium labeling method. These findings indicate that biocompatible Cur-MM-ISG has great potential in ophthalmic drug therapy.
Subject(s)
Curcumin/administration & dosage , Drug Delivery Systems , Gels/chemistry , Micelles , Ophthalmic Solutions/administration & dosage , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry , Polysaccharides, Bacterial/chemistry , Stearic Acids/chemistry , Animals , Calorimetry, Differential Scanning , Conjunctiva/drug effects , Cornea/drug effects , Crystallization , Curcumin/pharmacology , Drug Liberation , Endocytosis , Fluorescence , Humans , Hydrogen-Ion Concentration , Ophthalmic Solutions/pharmacology , Osmotic Pressure , Particle Size , Permeability , Rabbits , Rheology , Solutions , Static ElectricityABSTRACT
Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to load ORI in order to improve its release characteristics and bioavailability. Herein, MOF-5 was synthesized by the solvothermal method and direct addition method, and characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TG), Brunauer-Emmett-Teller (BET), and Dynamic Light Scattering (DLS), respectively. MOF-5 prepared by the optimal synthesis method was selected for drug-loading and in vitro release experiments. HepG2 cells were model cells. MTT assay, 4',6-diamidino-2-phenylindole (DAPI) staining and Annexin V/PI assay were used to detect the biological safety of blank carriers and the anticancer activity of drug-loaded materials. The results showed that nano-MOF-5 prepared by the direct addition method had complete structure, uniform size and good biocompatibility, and was suitable as an ORI carrier. The drug loading of ORI@MOF-5 was 52.86% ± 0.59%. The sustained release effect was reliable, and the cumulative release rate was about 87% in 60 h. ORI@MOF-5 had significant cytotoxicity (IC50:22.99 µg/mL) and apoptosis effect on HepG2 cells. ORI@MOF-5 is hopeful to become a new anticancer sustained release preparation. MOF-5 has significant potential as a drug carrier material.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Diterpenes, Kaurane/administration & dosage , Diterpenes, Kaurane/chemistry , Drug Carriers/chemistry , Metal-Organic Frameworks , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Drug Delivery Systems , Drug Liberation , Humans , Models, Molecular , Molecular Conformation , Molecular Structure , Spectrum Analysis , ThermogravimetryABSTRACT
Classical prescriptions are precious wealth left by ancient Chinese medical scientists. Moreover,they are also the important part of the treasure-house in Chinese medicine. Classical prescriptions have a long and rich history for human-use in China and play an important role in keeping people healthy. The state administration of traditional medicine of China published the Catalogue of Classical Prescriptions(first batch) in 2018. This measure has inspired the enthusiasm of Chinese medicine manufacturers to study ancient classical prescriptions and develop classical compound prescriptions. Based on the first batch of classical prescriptions, the dosage forms, sources, prescription components, decocting degree, use of toxic drugs and processing methods of classical prescriptions. The results showed that most of the classical prescriptions in the first batch were decoction and boiled powder,while only four of them were powder and paste forms,all of which were originated from representative classics in the past dynasties. The dosage and decocting degree of decoction were greater than those of boiled powder. The dosage and decocting degree of decoction in Han and Tang Dynasties was close to that in Ming and Qing Dynasties,higher than that in Song and Jin Dynasties. Moreover,the average number of herbs in the prescriptions in Han Dynasty was the smallest. The use of toxic traditional Chinese medicine was the most frequent in Han Dynasty, and Pinellia ternata was the most common toxic medicine. There were various processing methods, including cleansing, cutting, stir-frying, roasting and so on. In this paper, the dosage forms of traditional paste, the time concept of decoction in the ancient times, the traditional roasting method and the processing method of toxic drugs were summarized to provide ideas and reference for further development of classical prescriptions.