Microneedle-Assisted Percutaneous Delivery of a Tetramethylpyrazine-Loaded Microemulsion

Qiang, Zhang; Yu, Yinglan; Bi, Xiaolin; Zhang, Ren; Di, Liuqing

doi:10.3390/molecules22112022

Cited by 10 publications

(7 citation statements)

References 31 publications

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“…Alternatively, incorporating surfactants has been explored as a strategy, albeit less popular, to improve the fabrication process and overall performance of dissolving MAPs. − With this approach, the surfactant used functions mostly as an external plasticizer to reduce the overall rigidity and brittleness of the dissolving MAPs upon drying. Doing so enables the ease of demolding without fracturing the microneedle tips .…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Impact of Surfactants on the Performance of Dissolving Microneedle Array Patches

et al. 2022

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The need for biocompatible polymers capable of dissolving in the skin while exhibiting reasonable mechanical features and delivery efficiency limits the range of materials that could be utilized in fabricating dissolving microneedle array patches (MAPs). The incorporation of additives, such as surfactants, during microneedle fabrication might be an alternative solution to overcome the limited range of materials used in fabricating dissolving MAPs. However, there is a lacuna in the knowledge on the effect of surfactants on the manufacture and performance of dissolving MAPs. The current study explores the role of surfactants in the manufacture and performance of dissolving MAPs fabricated from poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) loaded with the model drugs, ibuprofen sodium and itraconazole. Three nonionic surfactants, Lutrol F108, Pluronic F88, and Tween 80, in solutions at varying concentrations (0.5, 1.0, and 2.0% w/w) were loaded into these dissolving MAPs. It was discovered that all of the dissolving MAPs that incorporated surfactant displayed a lower reduction in the microneedle height (≈10%) relative to the control formulation (≈20%) when subjected to a compressive force of 32 N. In addition, the incorporation of surfactants in some instances enhanced the insertion profile of these polymeric MAPs when evaluated using ex vivo neonatal porcine skin. The incorporation of surfactant into ibuprofen sodium-loaded dissolving MAPs improved the insertion depth of MAPs from 400 μm down to 600 μm. However, such enhancement was not apparent when the MAPs were loaded with the model hydrophobic drug, itraconazole. Skin deposition studies highlighted that the incorporation of surfactant enhanced the delivery efficiency of both model drugs, ibuprofen sodium and itraconazole. The incorporation of surfactant enhanced the amount of ibuprofen sodium delivered from 60.61% up to ≈75% with a majority of the drug being delivered across the skin and into the receptor compartment. On the other hand, when surfactants were added into MAPs loaded with the model hydrophobic drug itraconazole, we observed enhancement in intradermal delivery efficiency from 20% up to 30%, although this did not improve the delivery of the drug across the skin. This work highlights that the addition of nonionic surfactant is an alternative formulation strategy worth exploring to improve the performance and delivery efficiency of dissolving MAPs.

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Section: Introductionmentioning

confidence: 99%

Elucidating the Impact of Surfactants on the Performance of Dissolving Microneedle Array Patches

et al. 2022

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“…Arima et al have reported that the flux of 4-biphenylyl acetate, which is a prodrug of the non-steroidal anti-inflammatory drug, across tape-stripped skin was greater than that through full-thickness skin [ 40 ]. Furthermore, the tetramethylpyrazine microemulsion showed a two-fold increase in drug permeation across skin treated with microneedles compared with formulation alone [ 41 ]. A combination of microneedle with microemulsion to deliver celecoxib increased skin permeation more than microemulsion alone [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma

et al. 2023

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This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.

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“…However, there is little literature regarding the use of MNs in combination with microemulsions. Zu et al demonstrated that MN pretreatment in combination with drug-loaded microemulsions increased the percutaneous delivery of a hydrophilic compound both in vitro and in vivo (16). However, that study evaluated a single formulation; therefore, the effects of various formulation parameters were not considered.…”

Section: Discussionmentioning

confidence: 99%

“…However, little work has been done to evaluate drug delivery into the skin using drug-loaded microemulsions in combination with MNs. A recent study has shown that MN pretreatment increased systemic delivery of tetramethylpyrazine from a microemulsion formulation compared to microemulsion delivery through intact skin (16). This initial study shows the promise for combination treatment of microemulsions and MNs for cutaneous drug delivery.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Skin Retention and Drug Permeation through Intact and Microneedle Pretreated Skin after Application of Propranolol Loaded Microemulsions

Kelchen

Brogden

2018

Pharm Res

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Purpose Topical beta-blockers are efficacious for treating infantile hemangiomas, but no formulations have been specifically optimized for skin delivery. Our objective was to quantify skin concentrations and drug permeation of propranolol (a nonselective beta-blocker) after application of microemulsions to intact and microneedle pretreated skin. Methods Four propranolol-loaded microemulsions were characterized for droplet size, surface charge, conductivity, pH, drug solubility, and drug release. Skin concentrations and drug permeation through skin were quantified using LC-MS. Skin-to-receiver ratios were used to compare the microemulsion formulations to a drug-in-PBS solution. Results Propranolol solubility was significantly greater in microemulsions vs PBS. Cumulative drug release from the microemulsions over 24 h ranged from 13 to 26%. Skin concentrations and drug permeation through intact skin was significantly higher from PBS; however, the skin-to-receiver ratios were significantly higher for water-rich microemulsions compared to PBS or surfactant-rich microemulsions. Microneedle pretreatment significantly increased skin concentrations for all formulations. Skin-to-receiver ratios significantly increased after microneedle pretreatment for surfactant-rich microemulsions. Conclusions Microemulsion formulation can be altered to elicit different drug delivery profiles through MN-treated skin. This could be advantageous for maximizing local skin drug concentrations and improving dosing schedules for infantile hemangioma treatment.

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Microneedle-Assisted Percutaneous Delivery of a Tetramethylpyrazine-Loaded Microemulsion

Cited by 10 publications

References 31 publications

Elucidating the Impact of Surfactants on the Performance of Dissolving Microneedle Array Patches

Elucidating the Impact of Surfactants on the Performance of Dissolving Microneedle Array Patches

Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma

In Vitro Skin Retention and Drug Permeation through Intact and Microneedle Pretreated Skin after Application of Propranolol Loaded Microemulsions

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