Optimised NLC: a nanotechnological approach to improve the anaesthetic effect of bupivacaine

Silva, Gustavo Henrique Rodrigues da; Ribeiro, Lígia Nunes de Morais; Mitsutake, Hery; Guilherme, Viviane A.; Castro, Simone R.; Breitkreitz, Márcia Cristina; Paula, Eneida de

doi:10.1016/j.ijpharm.2017.06.066

Cited by 38 publications

(43 citation statements)

References 57 publications

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“…The blending procedure (hybridization) seemed not to affect the structural organization of the NLC, since XAN-NLC/LDC-PLC exhibited a bimodal LA release profile -with an initial high burst effect followed by sustained releasedecisive to achieve an optimized LA action. 41 The release of LDC was longer sustained than that of PLC in the hybrid hydrogels, in a similar way to the release from NLC suspensions. 7 The higher hydrophobic character and encapsulation efficiency by NLC could explain the differential release profile of LDC.…”

Section: Discussionmentioning

confidence: 57%

Nanohybrid hydrogels designed for transbuccal anesthesia

Ribeiro

Franz-Montan

Breitkreitz

et al. 2018

IJN

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BackgroundLocal anesthesia in dentistry is by far the most terrifying procedure for patients, causing treatment interruption. None of the commercially available topical formulations is effective in eliminating the pain and phobia associated to the needle insertion and injection.Materials and methodsIn this work we prepared a nanostructured lipid-biopolymer hydrogel for the sustained delivery of lidocaine–prilocaine (LDC-PLC) for transbuccal pre-anesthesia. The lipid was composed of optimized nanostructured lipid carriers (NLC) loaded with 5% LDC-PLC (NLC/LDC-PLC). The biopolymer counterpart was selected among alginate, xanthan (XAN), and chitosan matrices. The XAN-NLC hydrogel presented the most uniform aspect and pseudoplastic rheological profile, as required for topical use; therefore, it was selected for subsequent analyses. Accelerated stability tests under critical conditions (40°C; 75% relative humidity) were conducted for 6 months, in terms of drug content (mg/g), weight loss (%), and pH.ResultsIn vitro LDC-PLC release profile through Franz diffusion cells revealed a bimodal kinetics with a burst effect followed by the sustained release of both anesthetics, for 24 hours. Structural analyses (fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy) gave details on the molecular organization of the hybrid hydrogel, confirming the synergic interaction between the components. Safety and efficacy were evaluated through in vitro cell viability (3T3, HaCat, and VERO cells) and in vivo antinociceptive (tail-flick, in mice) tests, respectively. In comparison to a control hydrogel and the eutectic mixture of 5% LDC-PLC cream (EMLA®), the XAN-NLC/LDC-PLC hybrid hydrogel doubled and quadrupled the anesthetic effect (8 hours), respectively.ConclusionConsidering such exciting results, this multifaceted nanohybrid system is now ready to be further tested in clinical trials.

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Section: Discussionmentioning

confidence: 57%

Nanohybrid hydrogels designed for transbuccal anesthesia

Ribeiro

Franz-Montan

Breitkreitz

et al. 2018

IJN

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“…Also, based on the toxicological profile data, doses were calculated for dimethylacetamide derivatives. In case when toxicological studies and studies of local anesthetic effects were carried out in different specimen of animals, the dose conversion factors were used from (Freireich et al 1966).…”

Section: Substances and Drugsmentioning

confidence: 99%

“…Great progress has been made in the stereopharmacology of bupivacaine, ropivacaine, etc. (Da Silva et al 2017). However, it is becoming more important worldwide not just to develop novel effective molecules for a given type of local anesthesia, but rather to invent promising drug delivery systems (Riberio et al 2017), which would allow, first, localizing the pharmacological effect at most, secondly, managing the profile of unwanted effects, and, finally, bringing the efficacy and safety of anesthetic relief to a qualitatively new level.…”

Section: Introductionmentioning

confidence: 99%

On local anesthetic action of some dimethylacetamide compounds

Новиков¹,

Blinova²,

Семелева³

et al. 2018

RRP

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The study aim was to explore local anesthetic properties of some tertiary and quaternary derivatives of dimethylacetamide. Materials and methods. The study was performed on white laboratory mice and rats of both sexes, male Agouti guinea pigs, and isolated sciatic nerves of lake frog. In the focus of the study there were two quaternary and eight tertiary compounds of dimethylacetamide with substituted anion with some amino and carbonic acids residue. A local anesthetic property was predicted by computational analysis. Acute toxicity of the most promising substances was studied in mice through subcutaneous route. Local anesthetic activity of tertiary compounds LKhT-3-00, LKhT-4-00 and quaternary LKhT-12-02 was studied on models of terminal, infiltration and conduction anesthesia. The influence of substances on mixed nerve conduction was investigated on lake frog’s isolated sciatic nerves. Results and discussion. The greatest probability of the local anesthetic activity during computational analysis was estimated for the tertiary derivatives of dimethylacetamide LKhT-3-00 and LKhT-4-00 and for the quaternary compound LKhT-12-02. According to their toxicological profile, the compounds belong to moderately toxic substances (class 3). On the model of terminal and infiltration anesthesia, substances LKhT-3-00 and LKhT-4-00 at concentrations of 0.5-1% rapidly cause deep and prolonged anesthesia. On the models of conduction anesthesia, the quaternary derivative of dimethylacetamide LKhT-12-02 has the greatest analgesic effect. The duration of the effect of the substance is over 3 hours. All the investigated compounds block sciatic nerve conduction. The longest effect is registered for LKhT-12-02. Conclusions. Dimethylacetamide derivatives at concentrations of 0.5-1.0% exhibit a local anesthetic activity, and are effective for terminal, conduction and infiltration anesthesia. Their effect is due to blockade of nerve conduction.

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“…NLC are excellent carriers for LA, being able to prolong the anaesthesia time, as reported for different agents, mainly at topical administration [2,[13][14][15]. Local anaesthetics can be encapsulated into the lipid core of NLC in the poorly water-soluble, neutral (uncharged) form so that these formulations, unlike the commercial injectable LA formulas, have a pH above 7 [12].…”

Section: Introductionmentioning

confidence: 99%

Designed for Dentistry, Articaine in NLC Improves Anaesthesia at Inflamed Tissues

Silva¹,

Lemes²,

Geronimo³

et al. 2020

Proceedings of the 5th World Congress on Recent Advances in Nanotechnology

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Although used on a regular basis, local anaesthetics fail in places where inflammation is present, a problem for routine dental care. Intrinsic factors of the inflammatory process prevent anaesthetics from performing their function, at safe doses. The encapsulation of local anaesthetics in nanostructured lipid carriers (NLC) produces formulations with good physicochemical characteristics and improved anaesthetic effect. In that sense we developed an NLC formulation for articaine (ATC), a local anaesthetic with increasing use in dentistry. The developed formulation showed average particle sizes of 237.6 ± 3.3 nm, low polydispersity (PDI=0.169 ±0.015) and negative zeta potentials (-42.1 ± 0.5 mV), suitable for parenteral application. ATC was successfully encapsulated (%EE = 66.8 ± 2.3%) in such lipid nanocarriers. When tested in vivo, in a rodent carrageenan-induced inflammation model, NLC-ATC decreased by 35% the inflammatory hyperalgesia response, in relation to free articaine. These results had encouraged us to propose further clinical evaluation tests to test the formulation in dentistry.

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Optimised NLC: a nanotechnological approach to improve the anaesthetic effect of bupivacaine

Cited by 38 publications

References 57 publications

Nanohybrid hydrogels designed for transbuccal anesthesia

Nanohybrid hydrogels designed for transbuccal anesthesia

On local anesthetic action of some dimethylacetamide compounds

Designed for Dentistry, Articaine in NLC Improves Anaesthesia at Inflamed Tissues

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