ABSTRACT
Long-acting analgesia is a common clinical treatment method after surgery. The slow-release injection with long-acting analgesia has the advantages of less medication frequency and stable effect. In this study, the analgesic drug lappaconitine hydrobromide lyotropic liquid crystal injection was prepared, and its sustained release mechanism, drug release and pharmacodynamic characteristics were evaluated. The results of polarizing microscope and freeze-transmission electron microscope showed that the lyotropic liquid crystal injection of the liquid crystal precursor preparation of lappaconitine hydrobromide could be obtained by the combination of glycerol monooleate (GMO) and soybean lecithin (SPC) in different proportions. The results of dissolution study in vitro showed that the drug release rate of different forms of liquid crystal preparations was layered liquid crystal > cubic liquid crystal > hexagonal liquid crystal. The mathematical model fitting results of the release data showed that the external release of layered liquid crystal, cubic liquid crystal and hexagonal liquid crystal conforms to the Ritger-Peppas model, and the release mechanism was Fick diffusion. The results of pharmacodynamics study in vivo showed that the analgesic effect of lappaconitine hydrobromide lyotropic liquid crystal injection lasted for 3 days, and there was no abnormality in the incision and local tissue, showing good safety and tolerance. The study on drug release and elimination process of the in vivo gel repository showed that lappaconitine hydrobromide could be completely released from the lyotropic liquid crystal 3 days after administration, and the sustained-release materials could be gradually eliminated locally. All animal experiments were approved by the Experimental Animal Ethics Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences (No. 2021-08-GY-61) and the experiments were conducted in accordance with the relevant guiding principles and regulations. The lyotropic liquid crystal injection of lappaconitine hydrobromide prepared in this study presented a solution state at room temperature, and underwent phase transition in contact with the body fluid at the administration site, formed a drug depot and exerted a slow drug release effect. This preparation can reduce systemic toxicity, prolong the duration of analgesia, reduce the number of administrations, improve the compliance of postoperative patients, and provide a reference for the design of long-term sustained release analgesic preparations.
ABSTRACT
Lyotropic liquid crystal is an ordered system with various geometric shapes or three-dimensional structures formed by the interaction of amphiphilic molecules dissolved in polar solvents, and has the characteristics of excellent drug applicability, high drug loading, good bioadhesive property and high transdermal permeability. Through a comprehensive analysis of the research results in this research group and the related research reports of LLC drug delivery system, the authors systematically discussed the research value, development potential and research status of LLC in the field of new drug delivery system of traditional Chinese medicine(TCM), especially in the percutaneous and mucosal drug delivery system and the oral microparticle drug delivery system of TCM. At the same time, due to the current research field of TCM-LLC drug delivery system starts late, many of the basic research problems to be further perfect, this paper had carried on the induction summary to these problems, and put forward the research countermeasures:①the basic research of TCM-LLC drug delivery system should be strengthened by referencing the research experience and methods of LLC drug delivery system of single chemical component combined with TCM characteristics, ②the research on the release mechanism of the chemical components in TCM should be strengthened, and the basic research on the LLC drug delivery system of synchronized sustained release TCM should be carried out, ③development of new LLC materials applicable to TCM, ④the quality evaluation system of TCM-LLC should be improved, ⑤to explore the LLC preparation process suitable for industrialization.
ABSTRACT
Lyotropic liquid crystal(LLC) is generally a kind of micelle association formed by self-assembly of amphiphilic lipid polymers in polar solvents. It have been applied in the study of drug delivery of administration of oral, skin injection, ocular, and cavity channel routes(including buccal cavity, nasal cavity, vagina), et al. Medical liquid crystal mainly includes lamellar phase, inverse hexagonal phase and inverse cubic phase. Inner assembling order in different structures of liquid crystals will affect the drug localization, viscosity, molecular interactions, and further drug release in vitro and in vivo, pharmacokinetics and so on. Thus, it is very important to characterize their microstructures. In this article, the characterization methods of LLC microstructures are comprehensively described based on the research of LLC as drug delivery carrier and related literatures, which can provide reference for further study of LLC drug delivery system.
ABSTRACT
@#Lyotropic liquid crystal system is formed by the amphiphilic molecules dissolving in polar solvents with a special geometric structure. Lamellar, cubic and hexagonal mesophases are some of the most common lyotropic liquid crystal systems. Recently, they have attracted much research attention because of their distinctive structures and physico-chemical properties(like strong bioadhesion, high permeability, low liquidity, and slow released drug), and have been widely used as carriers for drug delivery systems, especially in transdermal and mucosal fields. According to the research about lyotropic liquid crystal and nasal route of administration in our group, and the related references in recent years, we investigate the technical strategies about the using of lyotropic liquid crystal in transdermal and mucosal drug delivery system. Among them, we specially put the emphasis on the application prospects of lyotropic liquid crystal in the nasal mucosal administration, and then provide a theoretical basis and future research directions in the development of lyotropic liquid crystal in transdermal and mucosal administration fields.