Entrapping bupivacaine-loaded emulsions in a crosslinked-hydrogel increases anesthetic effect and duration in a rat sciatic nerve block model

Davis, Brett; Erickson, Sierra; Wojtalewicz, Susan; Simpson, Andrew; Metcalf, Cameron S.; Sant, Himanshu; Shea, Jill E.; Gale, Bruce K.; Agarwal, Jayant P.

doi:10.1016/j.ijpharm.2020.119703

Cited by 11 publications

(13 citation statements)

References 36 publications

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“…The controlled release of the particles was evaluated using previously described methods. 15,16 In brief, 100 μL of each formulation ( n = 4) was placed into a 10 kDa dialysis bag with 1 mL of 1x PBS. The bags were then placed into 50 mL conical tubes filled with a 1xPBS sink.…”

Section: Methodsmentioning

confidence: 99%

“…The sink was sampled and completely replaced at predetermined timepoints: 24, 48, 72, 96, 144, 198, 228, 300 and 444 h. Drug concentrations of collected sink samples were quantified using ultraviolet visible spectrophotometer and analyzed at 272 nm using the 2 nd derivative noise reduction method. 15,16…”

Section: Methodsmentioning

confidence: 99%

“…13,14 However, current products are lacking in affordability and are controversial on efficacy. 15,16 Research indicates that the local anesthetic products with more robust material properties, namely higher viscosity, remain in the administration site for longer durations. Additionally, there is evidence that increased viscosity and the presence of microparticles may slow in vivo uptake by providing protection from phagocytic cells.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, there is evidence that increased viscosity and the presence of microparticles may slow in vivo uptake by providing protection from phagocytic cells. 16–19…”

Section: Introductionmentioning

confidence: 99%

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Evaluating the influence of particle morphology and density on the viscosity and injectability of a novel long-acting local anesthetic suspension

Wojtalewicz

Vizmeg

Erickson³

et al. 2022

J Biomater Appl

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Proper pain management is well understood to be one of the fundamental aspects of a healthy postoperative recovery in conjunction with mobility and nutrition. Approximately, 10% of patients prescribed opioids after surgery continue to use opioids in the long-term and as little as 10 days on opioids can result in addiction. In an effort to provide physicians with an alternative pain management technique, this work evaluates the material properties of a novel local anesthetic delivery system designed for controlled release of bupivacaine for 72 hours. The formulation utilizes solid-lipid microparticles that encapsulate the hydrophobic molecule bupivacaine in its free-base form. The lipid microparticles are suspended in a non-crosslinked hyaluronic acid hydrogel, which acts as the microparticle carrier. Two different particle manufacturing techniques, milling and hot homogenization, were evaluated in this work. The hot homogenized particles had a slower and more controlled release than the milled particles. Rheological techniques revealed that the suspension remains a viscoelastic fluid when loaded with either particle type up to 25% (w/v) particles densities. Furthermore, the shear thinning properties of the suspension media, hyaluronic acid hydrogel, were conserved when bupivacaine-loaded solid-lipid microparticles were loaded up to densities of 25% (w/v) particle loading. The force during injection was measured for suspension formulations with varying hyaluronic acid hydrogel concentrations, particle densities, particle types and particle sizes. The results indicate that the formulation viscosity is highly dependent on particle density, but hyaluronic acid hydrogel is required for lowering injection forces as well as minimizing clogging events.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Additionally, there is evidence that increased viscosity and the presence of microparticles may slow in vivo uptake by providing protection from phagocytic cells. 16–19…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluating the influence of particle morphology and density on the viscosity and injectability of a novel long-acting local anesthetic suspension

Wojtalewicz

Vizmeg

Erickson³

et al. 2022

J Biomater Appl

Self Cite

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“…Local anesthetics in gel formulations had been recently described for topical use [13][14][15]. However, a variety of systems in hydrogels have been also reported for injectable administration of bupivacaine [16,17], lidocaine [7,[18][19][20][21][22][23], and ropivacaine [6,24]. Additionally, local anesthetic-loaded PL-based hydrogels have been studied as matrices for inorganic compounds such as Ca/Na-rich bioglass [25], prodrug light-triggered release (Zhang et al, 2020), polymeric nanoparticles [26], and lanolin/oleic acid lipid-mixture [27].…”

Section: Introductionmentioning

confidence: 99%

Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation

Mariano

Papini

Faria

et al. 2021

BioMed Research International

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This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic. For this purpose, poloxamer- (PL-) based hydrogels were synthesized for evaluating the influence of polymer concentration, hydrophilic-lipophilic balances, and binary system formation on biopharmaceutical properties and pharmacological performance. Transition temperatures were shifted, and rheological analysis revealed a viscoelastic behavior with enhanced elastic/viscous modulus relationship ( G ’ / G ” = 1.8 to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model ( R 2 = 0.923 –0.989), indicating the drug diffusion from hydrogels to the medium. RVC-PL hydrogels were potentially biocompatible evoking low cytotoxic effects (in fibroblasts and Schwann cells) and mild/moderate inflammation signs on sciatic nerve nearby histological evaluation. In vivo pharmacological assays demonstrated that PL407 and PL407/338 evoked differential analgesic effects, by prolonging the sensory blockade duration up to ~340 and 250 min., respectively. All those results highlighted PL407 and PL407/338 as promising new strategies for sustaining analgesic effects during the postoperative period.

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Effect of Active Pharmaceutical Ingredient, Lipid Composition, and Thermal Processing on the Physical Stability of Local Anesthetic-loaded Lipid Microparticles

Erickson,

Vizmeg,

Shuckra

et al. 2023

J Pharm Innov

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Entrapping bupivacaine-loaded emulsions in a crosslinked-hydrogel increases anesthetic effect and duration in a rat sciatic nerve block model

Cited by 11 publications

References 36 publications

Evaluating the influence of particle morphology and density on the viscosity and injectability of a novel long-acting local anesthetic suspension

Evaluating the influence of particle morphology and density on the viscosity and injectability of a novel long-acting local anesthetic suspension

Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation

Effect of Active Pharmaceutical Ingredient, Lipid Composition, and Thermal Processing on the Physical Stability of Local Anesthetic-loaded Lipid Microparticles

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