Application of Advanced Technologies—Nanotechnology, Genomics Technology, and 3D Printing Technology—In Precision Anesthesia: A Comprehensive Narrative Review
Abstract
:1. Introduction
2. Application of Nanotechnology in the Anesthesia Field
2.1. Anesthesia and Nanotechnology
2.1.1. Nanotechnology in Inhalation Anesthesia
2.1.2. Nanotechnology in Local Anesthesia
Local Anesthetic Drugs | Nanoparticle Type | Application Path | Test Method | Results | Duration of Efficacy |
---|---|---|---|---|---|
Bupivacaine | 15 nm micellar bupivacaine formulation (M-Bup) and 100 nm liposomal bupivacaine formulation | Local anesthesia | Tail injection in rats [25] | It showed an extended residence time in the local vasculature, with M-Bup showing the most prominent effect; there was also a reduction in systemic drug distribution [25]. | M-Bup provides 4.5 h of local anesthesia [25]. |
Muhilamellar liposomes | Local anesthesia | Brachial plexus anesthesia in rabbits [28], intravenous drip in rabbits’ ears [29] | There was a prolonged effect of local anesthetics [28], with a significantly reduced drug toxicity to the central nervous system and heart [29]. | In the BP-MLV group, the plasma concentration of bupivacaine was lower within the first 10 min (p < 0.05) and higher after 24 h (p < 0.05). The radiolabeling in the BP group decreased between 4 and 24 h, while in the BP-MLV group, it decreased between 1 and 2 days [28]. | |
Polymerized alginate nanoparticles [27, 30], large multicapsular liposomes (Bupisome) encapsulated in Ca-alginate cross-linked hydrogels (Bupigel) | Local anesthesia | In vitro and in vivo testing in mice, physicochemical property determination [27], and subcutaneous injection in mice [30] | It has good stability, low cytotoxicity, and a strong intensity of action [27]. There was a prolonged duration of the analgesic effect [27,30], with Bupigel outperforming Bupisome. | BVC (bupivacaine) is completely released in the solution after 350 min (100%), while the complete release of BVC present in the nanoparticle takes a longer time [27]. | |
Large multivesicular vesicles | Local anesthesia | Healthy volunteers received subcutaneous injections [53] | Delayed elimination and prolonged redistribution of plasma results in prolonged pharmacodynamic effects [53]. | The time to reach the maximum plasma concentration of the liposomal formulation increased by 7-fold (262 +/− 149 min vs. 37.5 +/− 16 min, p < 0.01) [53]. | |
Liposomal bupivacaine (LEB) | Local anesthesia | Intra-articular soft tissue injection in dogs [54] | Dogs administered with LEB are less likely to require rescue analgesia and receive lower doses of opioid medications compared to dogs administered with 0.5 BH [54]. | In the LEB group, three dogs requiring rescue analgesia were identified at 8 h (n = 2) and 16 h (n = 1) post-extubation, based on a CSU-CAPS pain score ≥ 2. In the 0.5 BH group, among the 10 dogs requiring rescue analgesia, 7 dogs first exhibited these symptoms within 6 (n = 4) to 8 (n = 3) hours post-extubation [54]. | |
Liposomal suspension of bupivacaine | Local anesthesia | Sciatic nerve blockade in dogs [55] | The blockade characteristics of bupivacaine liposomal suspension are effective and long-lasting [55]. | In the treatment of 10 cases with bupivacaine with dexmedetomidine (BUP-DEX), all functions completely disappeared at 6 h. In all cases, all functions recovered within 96 h and 24 h after administration of bupivacaine liposome suspension (BLS) and BUP-DEX, respectively [55]. | |
Microcapsules | Local anesthesia | Assessment of catheter microdialysis in healthy volunteers [56] | The extended-release properties of microcapsules allow a prolonged duration of anesthesia [56]. | After injection of microcapsules, the concentration of bupivacaine increased within 24–34 h. After 96 h, 78% of the injection sites with microcapsules still had analgesic effects, significantly longer than the bupivacaine solution (p < 0.001) [56]. | |
Prilocaine | Liposomes | Local anesthesia for oral cavity | Maxillary infiltration anesthesia in healthy volunteers [31] | Prilocaine does not seem to benefit from liposome encapsulation [31]. | The median (and interquartile range) onset time for all formulations of gingival anesthesia was 2 (0) minutes, with no significant difference between them (p > 0.05) [31]. |
Liposomes complexed with hydroxypropyl-β-cyclodextrin | Local anesthesia | In vivo assessment of anesthetic effects in guinea pigs [32] | The duration of the anesthetic effect was negatively correlated with the initial lag time of PRL hydrochloride in the core of aqueous vesicles [32]. | Dual-loaded liposomes containing 2% of the total drug dose exhibited optimal therapeutic activity and were significantly superior to the corresponding 2% single-loaded vesicles. They not only showed the shortest onset time (100% blockade of reflexes at 5 min) but also the longest duration of anesthesia effect (100% blockade of reflexes at 35 min) [32]. | |
Lidocaine | Liposomes | Surface local anesthesia | Skin test on the palmar side of the forearm of volunteers [26] | Lidocaine liposome anesthesia has a longer duration than regular preparation [26]. | The average pain score of 5% liposomal lidocaine was higher than the non-liposomal 5% lidocaine formulation, but the difference reached statistical significance only at 15 min [26]. |
Lidocaine-Prilocaine | Hybrid Nano Film | Local anesthesia | Permeability test of porcine buccal mucosa, tail-flick test in mice [24] | It is more permeable and has a longer anesthetic effect; it is not cytotoxic to 3T3 and HACAT cell lines [24]. | The obtained material showed a sustained release profile of LDC-PLC for over 8 h, and the permeability of pig buccal mucosa was nearly double that of the control group. Then, the in vivo efficacy of the PCT/NLC formulation was compared to biopolymer films and commercial drugs, demonstrating the longest anesthetic effect (>7 h) in mice through a tail flick test [24]. |
Mepivacaine | Liposomes | Oral local anesthesia | Oral injection [33], oral maxillary infiltration [34] in healthy volunteers | It extends the duration of anesthesia, reduces injection discomfort [33], and allows systemic absorption similar to that of vasoconstrictor local anesthesia [34]. | Healthy volunteers experienced median ranges of induction latency (LP) (2–8 min), pulpal anesthesia (PA) (20–45 min), and soft tissue anesthesia (STA) (120–180 min) after infiltration anesthesia with the following formulations of lidocaine: MVC 2%EPI, MVC 2%LUV, MVC 3%LUV, and MVC 3% [33]. |
Ropivacaine | Liposomes | Oral local anesthesia | Maxillary infiltration in healthy volunteers [35] | Liposome formulations lack vasoconstrictors and may be a safer alternative [35]. | They observed a maximum drug concentration (Tmax) of 50 (±14.1) minutes [35]. |
Tetracaine (TTC) | Polymeric nanoparticles (PLA NPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) | Local anesthesia | In vitro and in vivo tests in mice [57] | Each system has its advantages, with TTC NLCs being the more promising system for long-term anesthesia [57]. | Free TTC demonstrated complete permeation within 8 h, while TTC NLC showed lower permeation rates than TTC PLA NPs in the first 12 h but higher permeation rates than PLA NPs after 12 to 72 h. TTC SLNs provided the most effective in vitro permeation, with sustained efficiency lasting until the end of 72 h [57]. |
2.1.3. Nanotechnology in Perioperative Pain Management
3. Genomics and Anesthesia
3.1. Pharmacogenomics
3.1.1. CYP1
3.1.2. CYP2
CYP2C9
CYP2C19
CYP2D6
- Opioids
- Antiemetic
- Beta-blockers
3.1.3. CYP3
3.2. Disease Genomics
3.3. Decision Modeling
4. Research and Application of 3D Printing in the Anesthesia Field
4.1. Three-Dimensional Printing Technology
4.2. Three-Dimensional Printing and Anesthesia
4.2.1. Three-Dimensional Printing and Anatomical Models
4.2.2. Three-Dimensional Printing and Anesthesia Equipment
5. Future, Limitations, and Outlook of Precision Anesthesia
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug Classification | Representative Drugs | CYP450 Metabolizing Enzymes [108,109,110,111,112,113] | Other Special Genes | |
---|---|---|---|---|
Related Genes | Related Variant Subtypes | |||
Local anesthetics | Lidocaine Ropivacaine | CYP1A2 CYP3A4 CYP3A5 | CYP1A2 a: Thr83Met, lu168Gln, Phe186Leu, Ser212Cys, Gly299Ala, hr438Ile [114] | SCN5A b [115] MC1R c [116] |
Benzodiazepines | Midazolam Diazepam | CYP2C19 CYP3A4 CYP3A5 | CYP2C19 *2/*3/*17 CYP3A4 *1B CYP3A5 *1/*3/*6/*7 | - |
Inhalation of narcotics | Halothane Sevoflurane Isoflurane | CYP2E1 | CYP2E1 *1A/*5B/*6/*7B | RYR1 d [117] MC1R [118] |
Opioid analgesics | Fentanyl | CYP2D6 | CYP2D6 1/*2/*3/*4/*5/*6/*10/*17/*35/*41 [119] CYP3A4 *1/*1G CYP3A5 *1/*3 [120] CYP2B6 *6 | COMTb e [121] UGTb f [122] ABCB1b g OPRM1b h [123] OPRK1b i MDR1 [124] |
Codeine | CYP2B6 | |||
Morphine | CYP3A4 | |||
Tramadol | CYP3A5 CYP1C2 CYP1D2 CYP2B11 CYP2C41 CYP2D2 CYP2D15 [125,126] | |||
Intravenous anesthetics | Propofol | CYP2B6 CYP2C9 | CYP2B6 *4/*6 CYP2C9 *2 | UGT1A9 [111] GABA [127] |
Non-steroidal anti-inflammatory drugs | Aspirin Celecoxib | CYP2C8 CYP2C9 | CYP2C8 *1/*2/*3 CYP2C9 *1/*2/*3 | PTGS1 PTGS2 j [128] |
Neuromuscular blocking drugs | Succinylcholine Vecuronium-Bromide Rocuronium | CYP3A4 CYP2C19 | - | BCHE k [129] SLCO1B1 ABCB1 [115] RYR1 nAChR l [130] |
Anticoagulants | Warfarin Clopidogrel | CYP2C9 CYP2C19 | CYP2C9 *1/*2/*3 CYP2C19 *1/*2/*3/*9/*12/*14/*17 [130] | VKORC1 m [131] |
Antiemetic | Tropisetron Granisetron | CYP2D6 CYP3A4 | CYP2D6 *1/*2/*3/*4/*5/*6/*9/*41 | 5-HT3B [132] ABCB1 SLC22A1 n |
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Gu, S.; Luo, Q.; Wen, C.; Zhang, Y.; Liu, L.; Liu, L.; Liu, S.; Chen, C.; Lei, Q.; Zeng, S. Application of Advanced Technologies—Nanotechnology, Genomics Technology, and 3D Printing Technology—In Precision Anesthesia: A Comprehensive Narrative Review. Pharmaceutics 2023, 15, 2289. https://doi.org/10.3390/pharmaceutics15092289
Gu S, Luo Q, Wen C, Zhang Y, Liu L, Liu L, Liu S, Chen C, Lei Q, Zeng S. Application of Advanced Technologies—Nanotechnology, Genomics Technology, and 3D Printing Technology—In Precision Anesthesia: A Comprehensive Narrative Review. Pharmaceutics. 2023; 15(9):2289. https://doi.org/10.3390/pharmaceutics15092289
Chicago/Turabian StyleGu, Shiyao, Qingyong Luo, Cen Wen, Yu Zhang, Li Liu, Liu Liu, Su Liu, Chunhua Chen, Qian Lei, and Si Zeng. 2023. "Application of Advanced Technologies—Nanotechnology, Genomics Technology, and 3D Printing Technology—In Precision Anesthesia: A Comprehensive Narrative Review" Pharmaceutics 15, no. 9: 2289. https://doi.org/10.3390/pharmaceutics15092289