Emulsion-induced polymersomes taming tetrodotoxin for prolonged duration local anesthesia
Xiaosi Li1, Qi Li1, Shenghan Song2
1Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, AL 35487, USA.
Advanced Therapeutics
|February 23, 2023
Summary
Emulsion-induced polymersomes safely deliver tetrodotoxin (TTX) for prolonged local anesthesia. This novel drug delivery system enables a 22-day nerve block with minimal toxicity, offering new hope for pain management.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Pharmacology
Background:
- Injectable local anesthetics are crucial for managing post-operative and chronic pain.
- Tetrodotoxin (TTX), a potent sodium channel blocker, offers prolonged nerve blockade but is limited by systemic toxicity.
- Developing safe and effective delivery systems for TTX is essential for its clinical application.
Purpose of the Study:
- To develop and evaluate emulsion-induced polymersomes (EIP) as a novel drug delivery system for tetrodotoxin (TTX).
- To assess the safety and efficacy of EIP-encapsulated TTX for achieving long-lasting local anesthesia.
- To investigate the potential of EIP/TTX for sustained drug release and reduced systemic toxicity.
Main Methods:
- Hyperbranched polyglycerol-poly(propylene glycol)-hyperbranched polyglycerol (HPG-PPG-HPG) was used to form polymersomes encapsulating TTX via emulsion.
- Encapsulation efficiency and structural stability of the polymersomes were analyzed.
- In vivo studies in Sprague-Dawley rats assessed TTX tolerability, systemic toxicity, and sciatic nerve block duration with and without sodium octyl sulfate (SOS).
Main Results:
- HPG-PPG-HPG self-assembled into polymersomes with high TTX encapsulation efficiency (up to 94%).
- The EIP/TTX formulation significantly increased the tolerated dose of TTX in rats, preventing systemic toxicity.
- A single perineural injection of EIP/TTX/SOS achieved a reliable sciatic nerve block lasting 22 days with minimal local toxicity.
Conclusions:
- Emulsion-induced polymersomes provide a stable and effective platform for delivering tetrodotoxin for local anesthesia.
- This EIP/TTX/SOS formulation demonstrates potential for long-duration pain management with an improved safety profile.
- The developed system overcomes TTX toxicity limitations, paving the way for advanced pain control strategies.
Related Concept Videos
01:27Local Anesthetics: Chemistry and Structure-Activity Relationship
4.5K
Local anesthetics (LAs) are drugs that induce a temporary loss of sensation in a limited body area, preventing pain. Cocaine was the first local anesthetic discovered in the late 19th century. Cocaine is a benzoic acid ester obtained from the leaves of coca shrubs and was often used for its psychotropic effects. Cocaine was first isolated in 1860 by Albert Niemann. Sigmund Freud studied the physiological actions of cocaine. Carl Koller later introduced it into clinical practice in 1884 as a...
4.5K
01:23Local Anesthetics: Common Agents and Their Applications
504
Local anesthetics (LAs) are commonly used for various applications in medical and dental procedures. Some of the common agents used are cocaine, lidocaine, and bupivacaine.
Cocaine is an ester of benzoic acid and methylecgogine. It is used to anesthetize and vasoconstrict locally. Currently, it is used primarily for topical applications. It is beneficial for surgeries on the upper respiratory tract, providing anesthesia and shrinking the mucosa. Cocaine in the form of cocaine hydrochloride is...
Cocaine is an ester of benzoic acid and methylecgogine. It is used to anesthetize and vasoconstrict locally. Currently, it is used primarily for topical applications. It is beneficial for surgeries on the upper respiratory tract, providing anesthesia and shrinking the mucosa. Cocaine in the form of cocaine hydrochloride is...
504
01:13Local Anesthetics: Pharmacokinetics
824
The potency and duration of action of local anesthetics (LAs) are determined by their pharmacokinetics. Pharmacokinetics describes how LAs are absorbed, distributed, metabolized, and eliminated from the body. When administered to the vascular tissues, LAs are quickly absorbed and enter the systemic circulation, reducing their localized effects. Adding vasoconstrictors such as epinephrine to LAs reduces their absorption into the systemic circulation, making them clinically effective. The...
824
01:30Local Anesthetics: Clinical Application as Surface, Infiltration, and Conduction Block Anesthesia
1.2K
Depending on the target organ, local anesthetics (LAs) can be administered via various routes. In surface anesthesia, LAs are applied directly to the surface of the skin or mucous membranes. It is widely used for topical skin numbing before venipuncture or minor surgical procedures. Commonly used surface local anesthetics are lidocaine or benzocaine sprays or creams. Surface anesthesia occurs within 5 minutes and lasts for about 60 minutes. One of the main disadvantages of topical anesthesia is...
1.2K
01:23Local Anesthetics: Mechanism of Action
2.3K
Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
2.3K
01:29Local Anesthetics: Clinical Application as Epidural Anesthesia
474
Epidural anesthetics are administered in the fat-filled epidural space, the outermost part of the spinal canal. This technique is commonly employed for pain management and anesthesia during lower abdomen and pelvis surgeries or labor and delivery.
Since epidural anesthetics can be infused through an epidural catheter, all types of drugs, including short-acting ones, can be administered. Chloroprocaine and lidocaine are examples of short and long-duration anesthetics, respectively. Bupivacaine...
Since epidural anesthetics can be infused through an epidural catheter, all types of drugs, including short-acting ones, can be administered. Chloroprocaine and lidocaine are examples of short and long-duration anesthetics, respectively. Bupivacaine...
474