Preparation and investigation of a novel levobupivacaine <i>in situ</i> implant gel for prolonged local anesthetics

Zhao, Yanjing; Zhou, Long; Chen, Zhigang; Yang, Lei; Shi, Hong

doi:10.3109/21691401.2016.1160406

Cited by 10 publications

(4 citation statements)

References 21 publications

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“…Even though the injection of local anesthetic agents able to cause reversible nerve blockage is routinely used to reduce postsurgical pain and other pain‐intensive conditions, they become ineffective after a few short hours. In many instances, this limitation is simply, but also inadequately dealt with, by increasing the anesthetics dose . Recently, environmentally responsive polymers, especially reverse thermo‐responsive gels were used as injectable drug delivery systems .…”

Section: Physical Phenomenamentioning

confidence: 99%

In Situ Generated Medical Devices

Cohn

Sloutski

Elyashiv

et al. 2019

Adv Healthcare Materials

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Medical devices play a major role in all areas of modern medicine, largely contributing to the success of clinical procedures and to the health of patients worldwide. They span from simple commodity products such as gauzes and catheters, to highly advanced implants, e.g., heart valves and vascular grafts. In situ generated devices are an important family of devices that are formed at their site of clinical function that have distinct advantages. Among them, since they are formed within the body, they only require minimally invasive procedures, avoiding the pain and risks associated with open surgery. These devices also display enhanced conformability to local tissues and can reach sites that otherwise are inaccessible. This review aims at shedding light on the unique features of in situ generated devices and to underscore leading trends in the field, as they are reflected by key developments recently in the field over the last several years. Since the uniqueness of these devices stems from their in situ generation, the way they are formed is crucial. It is because of this fact that in this review, the medical devices are classified depending on whether their in situ generation entails chemical or physical phenomena.

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Section: Physical Phenomenamentioning

confidence: 99%

In Situ Generated Medical Devices

Cohn

Sloutski

Elyashiv

et al. 2019

Adv Healthcare Materials

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“…Organogels are formed by structurants of low molecular weight and some organic solvents that are supported, through a three-dimensional network, forming the gel. Since organogels are biodegradable, they can be used in drugs as protein carriers and vaccines for example [33][34][35].…”

Section: Definitions and Mechanismsmentioning

confidence: 99%

Conventional and Unconventional Crystallization Mechanisms

Chaves¹,

Silva²,

Domingues³

et al. 2019

Crystal Growth

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Understanding the crystallization behavior of fats and oils is essential to ensure certain desirable characteristics in a given industrial application. In recent years, some advances in the structuring of lipid phases have enabled a direct influence on the food properties. The structuring mechanisms of lipid bases can be classified as either conventional or unconventional. Conventional crystallization mechanisms consist of nucleation, growth, and maturation of the crystals, thus resulting in a crystalline lattice. Co-crystallization or seeding agents and emerging technologies such as ultrasound can be used to aid in crystallization and improve the physical properties of fats and oils. Unconventional mechanisms bring organogel technology as a trend, which consists in the use of self-assembly agents to entrap the liquid oil, resulting in a structured gel network. In this chapter, the formation process of crystalline networks and gel networks will be presented in stages, highlighting the main differences related to the mechanisms of formation and stabilization of both types of networks.

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“…In recent years, efforts to develop a novel long-acting local anesthetic included research on new drug molecules (Padera et al, 2006; Lim et al, 2007; Ries et al, 2009; Rodriguez-Navarro et al, 2011; Banerjee et al, 2015; Zhang et al, 2017b), adjuvant drugs (Kito et al, 1998; Sakamoto et al, 2016; Zhang et al, 2018), and sustained-release formulations (Ohri et al, 2013; Ramos Campos et al, 2013; Burbridge and Jaffe, 2015; Zhao et al, 2017b). In previous studies, we showed that QX-OH (Invention Patent, China, ZL201410688865.1), a quaternary lidocaine derivative, maintained the local anesthetic effect over a long period in rats (Zhang et al, 2017b).…”

Section: Introductionmentioning

confidence: 99%

The Preclinical Pharmacological Study of a Novel Long-Acting Local Anesthetic, a Fixed-Dose Combination of QX-OH/Levobupivacaine, in Rats

et al. 2019

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Introduction: Previous studies demonstrated that 35 mM QX-OH/10 mM Levobupivacaine (LL-1), a fixed-dose combination, produced a long-acting effect in rat local anesthesia models. All preclinical pharmacodynamic results indicated that LL-1 had potential for postsurgical pain treatment. The objective of this study was to investigate the pharmacokinetics of LL-1. Then, the possible mechanism of the extended duration by the combination was examined. Methods and Results: All experiments were examined and approved by the Committee of Animal Care of the West China Hospital Sichuan University (Ethical approval number, 2015014A). The compound action potentials were recorded to verify the pharmacodynamic result in ex vivo. In frog sciatic nerve, LL-1 produced an effective inhibition with rapid onset time. The concentration-time profiles of LL-1 were determined in plasma and local tissues after sciatic nerve block. The maximum concentration of QX-OH and levobupivacaine were 727.22 ± 43.38 µg/g and 256.02 ± 28.52 µg/g in muscle, 634.26 ± 36.04 µg/g and 429.63 ± 48.64 µg/g in sciatic nerve, and 711.71 ± 25.14 ng/ml and 114.40 ± 10.19 ng/ml in plasma, respectively. The absorption of QX-OH into circulation was very rapid at 0.71 ± 0.06 h, which was faster than that of levobupivacaine (4.11 ± 0.39 h, p = 0.003). The half-time of QX-OH in plasma and local tissues had no significant difference (p = 0.329), with the values of 2.64 h, 3.20 h, and 3.79 h in plasma, muscle, and sciatic nerve, respectively. The elimination profile of levobupivacaine differed from that of QX-OH, which was slower eliminated from plasma (4.89 ± 1.77 h, p = 0.036) than from muscle (1.38 ± 0.60 h) or sciatic nerve (1.28 ± 0.74 h). When levobupivacaine was used alone, the Tmax in plasma was 1.07 ± 0.16 h. Interestingly, the Tmax of levobupivacaine in the plasma was increased by four times in combination with QX-OH (4.11 ± 0.39 h). Levobupivacaine promotes cellular QX-OH uptake. Conclusion: The preclinical pharmacokinetic study of LL-1 in the rat plasma, muscle, and sciatic nerve was accomplished. Then, the possible mechanism of the prolonged duration was that QX-OH delayed the absorption of levobupivacaine from the injection site into circulation, and levobupivacaine accelerated QX-OH to accumulate into cells.

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Preparation and investigation of a novel levobupivacaine in situ implant gel for prolonged local anesthetics

Cited by 10 publications

References 21 publications

In Situ Generated Medical Devices

In Situ Generated Medical Devices

Conventional and Unconventional Crystallization Mechanisms

The Preclinical Pharmacological Study of a Novel Long-Acting Local Anesthetic, a Fixed-Dose Combination of QX-OH/Levobupivacaine, in Rats

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