Etravirine-loaded dissolving microneedle arrays for long-acting delivery

Rojekar, Satish; Vora, Lalitkumar K.; Tekko, Ismaiel A.; Volpe‐Zanutto, Fabiana; McCarthy, Helen; Vavia, Pradeep R.; Donnelly, Ryan F.

doi:10.1016/j.ejpb.2021.04.024

Cited by 70 publications

(32 citation statements)

References 69 publications

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“…The drug content in AmB-NE-DMN was quantified by dispersing DMN patch into a glass vial containing 10 mL water, sonicated for 15 min, and diluted with 10 mL methanol, followed by sonicated for a further 15 min. Then, 200 μL was taken into 1.5 mL tubes and mixed with 0.8 mL acetonitrile to precipitate PVP polymer while the drug remained dissolved [ 37 ]. This dispersion was centrifuged at 14,800 rpm for 10 min, and the supernatant was collected for HPLC analysis.…”

Section: Methodsmentioning

confidence: 99%

Nanoemulsion-based dissolving microneedle arrays for enhanced intradermal and transdermal delivery

Nasiri

Vora

Ershaid

et al. 2021

Drug Deliv. and Transl. Res.

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The development of dissolving microneedles (DMN) is one of the advanced technologies in transdermal drug delivery systems, which precisely deliver the drugs through a rapid dissolution of polymers after insertion into the skin. In this study, we fabricated nanoemulsion-loaded dissolving microneedle (DMN) arrays for intradermal and transdermal drug delivery. For this task, model drug (amphotericin B, AmB)-loaded nanoemulsion (NE) were prepared by the probe-sonication method. AmB-loaded-NE was prepared using Capmul MCM C-8 EP/NF, Tween® 80, poly(vinyl alcohol) (PVA-10 kDa), and poly (vinyl pyrrolidone) (PVP-360 kDa or K29/32) by using SpeedMixer™, followed by probe-sonication and evaluated for particle size and polydispersity index (PDI). Transmission electron microscopy (TEM) was also used to assess the particle size before and after DMN casting. AmB-NE embedded DMN arrays were found to be strong enough, revealed efficient skin insertion, and penetrated down to the fourth layer (depth ≈ 508 μm) of Parafilm M® (validated skin model). Ex vivo skin deposition experiments in full-thickness neonatal porcine demonstrated that after 24 h, AmB-NE-DMN arrays were able to deposit 111.05 ± 48.4 µg/patch AmB into the skin. At the same time, transdermal porcine skin permeation studies showed significantly higher permeability of AmB (29.60 ± 8.23 μg/patch) from AmB-NE-DMN compared to MN-free AmB-NE patches (5.0 ± 6.15 μg/patch) over 24 h. Antifungal studies of optimized AmB-NE-DMN, AmB-loaded discs and drug-free DMN against Candida albicans, confirmed the synergistic activity of Campul-MCM C-8, used in the nanoemulsion formulation. This study establishes that nanoemulsion based dissolving microneedle may serve as an efficient system for intradermal as well as transdermal drug delivery. Graphical abstract

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Section: Methodsmentioning

confidence: 99%

Nanoemulsion-based dissolving microneedle arrays for enhanced intradermal and transdermal delivery

Nasiri

Vora

Ershaid

et al. 2021

Drug Deliv. and Transl. Res.

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“…Images of the needles removed for testing and the remaining baseplate are shown in the article by Li et al [68]. Additionally, Rojekar et al described the procedures performed with solvent gradients (acetonitrile:water) to promote the precipitation of the polymers and PVA/PVP and, thus, allow the quantification of etravirine without interference from the MN matrix [70].…”

Section: Drug or Protein Contentmentioning

confidence: 99%

“…Regarding the mode of application, this can be conducted manually, with the aid of applicators previously calibrated to a single force value or with the equipment described in the mechanical characterization tests. Interestingly, some studies employed the same parameters in both tests, while others used the failure force value obtained to define the application force in the insertion test or to choose the most promising device in terms of mechanical resistance [38,41,51,56,70]. In addition to insertion force and mechanical strength, MN insertion capability is influenced by needle geometry and skin fixation support.…”

Section: Mechanical Properties In Vitro Assaysmentioning

confidence: 99%

“…As shown in Figure 6C, in comparison to the analyses of the nanostructured systems after their preparation, the stability studies investigated the maintenance of particle size (n = 19) and, less frequently, the polydispersity index (n = 9) and morphological appearance by TEM (n = 8) after insertion into the MN. The maintenance of MN mechanical characteristics was measured in 3 studies [70,77,78]. Considering all the stability studies, it is important to note that 40.74% reported the follow-up times after MN preparation, and 29.63% reported the storage temperature of the MN.…”

Section: Stability Assaysmentioning

confidence: 99%

“…Significant differences were also observed between the number of studies that characterized the nanostructured systems in terms of particle size, PDI, and zeta potential, before and after mixing in the MN polymer matrix. One possible cause for this difference relates to analytical limitations, as some studies highlighted that the polymer could interfere with the analysis [63,70]. Nevertheless, only 40.3% of the studies described the determination of the content of the substances in the MN.…”

Section: Assays Employed In Mn Analysismentioning

confidence: 99%

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Dissolving Microneedles Developed in Association with Nanosystems: A Scoping Review on the Quality Parameters of These Emerging Systems for Drug or Protein Transdermal Delivery

2021

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The largest organ of the body provides the main challenge for the transdermal delivery of lipophilic or high molecular weight drugs. To cross the main barrier of the skin, the stratum corneum, many techniques have been developed and improved. In the last 20 years, the association of microneedles with nanostructured systems has gained prominence for its versatility and for enabling targeted drug delivery. Currently, the combination of these mechanisms is pointed to as an emerging technology; however, some gaps need to be answered to transcend the development of these devices from the laboratory scale to the pharmaceutical market. It is known that the lack of regulatory guidelines for quality control is a hindrance to market conquest. In this context, this study undertakes a scoping review of original papers concerning methods applied to evaluate both the quality and drug/protein delivery of dissolving and hydrogel-forming microneedles developed in association with nanostructured systems.

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