Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate

Kaur, Monika; Ita, Kevin; Popova, Inna E.; Parikh, Sanjai J.; Bair, Daniel A.

doi:10.1016/j.ejpb.2013.10.007

Cited by 86 publications

(64 citation statements)

References 36 publications

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“…34) SEM images also demonstrate that MNs successfully puncture and create obvious micropores on the skin, indicative of SC barrier disruption. 17,[39][40][41][42] This finding could imply that these micropores can serve as a significant pathway for the transportation of molecules across the skin. In addition, CLSM images also suggest that MN can effectively facilitate FD-4 transport into the skin as a result of SC opening.…”

Section: Discussionmentioning

confidence: 98%

The Combination of Microneedles with Electroporation and Sonophoresis to Enhance Hydrophilic Macromolecule Skin Penetration

Petchsangsai

Rojanarata

Opanasopit

et al. 2014

Biological & Pharmaceutical Bulletin

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The objective of the present work was to investigate the effects of 3 combinatorial techniques (microneedle (MN), electroporation (EP), and sonophoresis (SN)) on the in vitro skin permeation of the hydrophilic macromolecular compound fluorescein isothiocyanate-dextran (FD-4; molecular weight (MW) 4.4 kDa). Assessment of the in vitro skin permeation of FD-4 was performed in porcine skin. MN, EP, and SN were used as physical enhancement methods, given the potential of their various mechanisms. The total cumulative amount of FD-4 that permeated through treated skin using 2 or 3 combined methods, i.e., MN EP, MN SN, EP SN, and MN EP SN, was investigated. Microconduits created by MN alone and in combination with the other techniques were observed under confocal laser scanning microscopy (CLSM). The histology of the treated skin was examined. In vitro skin permeation experiments revealed that the total cumulative amount of FD-4 that permeated porcine skin using 3 combined techniques (MN EP SN) was greater than the amount observed using a single method or 2 combinations (MN EP, MN SN, SN EP). The histological images indicate no noticeable damage in the skin treated with all of the enhancement methods. These results suggest that MN EP SN may serve as a potentially effective combination strategy to transdermally deliver various hydrophilic macromolecules without causing structural alterations or skin damage.Key words microneedle; electroporation; sonophoresis; hydrophilic macromolecule; fluorescein isothiocyanate-dextran Skin is the largest organ in our bodies, covering an area of approximately 2 m 2 and providing contact between our bodies and the external environment. The main function of skin is to act as a barrier to prevent the loss of tissue water and the entrance of foreign molecules. 1) The barrier properties of skin are attributed to the outermost layer, the stratum corneum (SC), which is highly hydrophobic. Although SC is 10-20 µm thick, it only allows small, potent lipophilic drugs to permeate the skin. Most hydrophilic macromolecules, such as peptides and proteins, are unable to permeate passively. Therefore, enhancement techniques are required to assist in the transport of such macromolecules across the skin. 2,3) In this study, physical enhancement methods were intentionally highlighted, including microneedles (MN), electroporation (EP), and sonophoresis (SN). Although the implementation of these methods is different, they mutually seek to bypass or remove the SC. 4) MN are micron-sized needles that can breach the SC to create holes large enough for various molecules to pass through. The average needle lengths range from 100 to 1500 µm, which is long enough to pierce the SC and upper layers of viable epidermis. Nevertheless, the needles do not puncture the deeper dermis layer, where numerous nerve endings are located. In other words, the needles are minimally invasive and do not create a sense of pain. Interestingly, the needle holes are considerably larger than macromolecular sizes; therefore, the macromol...

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Section: Discussionmentioning

confidence: 98%

The Combination of Microneedles with Electroporation and Sonophoresis to Enhance Hydrophilic Macromolecule Skin Penetration

Petchsangsai

Rojanarata

Opanasopit

et al. 2014

Biological & Pharmaceutical Bulletin

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“…The receptor fluid was continuously, magnetically stirred during the studies. The procedure followed Bpoke and patch^mechanism where micropores were created by insertion and removal of the microneedles before the drug formulation was applied [19]. Microneedles were manually inserted at the desired skin treatment site and removed after 1 min in an identical protocol as in dye binding studies.…”

Section: In Vitro Permeation Studies Using Vertical Franz Diffusion Cmentioning

confidence: 99%

“…Molecules can be placed at a desired depth in the skin [5] with relatively low microbial ingress [18] using needles of various lengths. Increase in microneedle density, insertion time, length, number of applications [19,20], and force of insertion [21] have been reported to increase the in vitro diffusion rate of drugs across the skin. Microneedle treatment significantly enhanced the transdermal delivery of PEGylated naltrexone prodrug [22], nanoencapsulated dye [23], verapamil hydrochloride and amlodipine [19], and mannitol [11].…”

Section: Introductionmentioning

confidence: 98%

Enhanced skin delivery of vismodegib by microneedle treatment

Nguyen

Banga

2015

Drug Deliv. and Transl. Res.

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The present study investigated the effects of microneedle treatment (maltose microneedles, Admin Pen™ 1200, and Admin Pen™ 1500) on in vitro transdermal delivery of vismodegib with different needle lengths, skin equilibration times, and microneedle insertion durations. The influence of microneedle treatment on the dimensions of microchannels (dye binding, calcein imaging, histology, and confocal microscopy studies), transepidermal water loss, and skin permeability of vismodegib was also evaluated. Skin viscoelasticity was assessed using a rheometer, and microneedle geometry was characterized by scanning electron microscopy. Permeation studies of vismodegib through dermatomed porcine ear skin were conducted using vertical Franz diffusion cells. Skin irritation potential of vismodegib formulation was assessed using an in vitro reconstructed human epidermis model. Results of the in vitro permeation studies revealed significant enhancement in permeation of vismodegib through microneedle-treated skin. As the needle length increased from 500 to 1100 and 1400 μm, drug delivery increased from 14.50 ± 2.35 to 32.38 ± 3.33 and 74.40 ± 15.86 μg/cm(2), respectively. Positive correlation between drug permeability and microneedle treatment duration was observed. The equilibration time was also found to affect the delivery of vismodegib. Thus, changes in microneedle length, equilibration time, and duration of treatment altered transdermal delivery of vismodegib.

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“…This enhancement of amlodipine besylate flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05 mg/cm 2 /hr in comparison to passive diffusion flux of 0.19 mg/cm 2 /hr [17]. The difference in flux values was also statistically significant.…”

Section: Metal Microneedlesmentioning

confidence: 88%

“…Metal microneedles can be made from different metals including stainless steel [17,38,39] (Fig. 3) and titanium [40e43].…”

Section: Metal Microneedlesmentioning

confidence: 99%

Transdermal delivery of drugs with microneedles: Strategies and outcomes

Ita

2015

Journal of Drug Delivery Science and Technology

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Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate

Cited by 86 publications

References 36 publications

The Combination of Microneedles with Electroporation and Sonophoresis to Enhance Hydrophilic Macromolecule Skin Penetration

The Combination of Microneedles with Electroporation and Sonophoresis to Enhance Hydrophilic Macromolecule Skin Penetration

Enhanced skin delivery of vismodegib by microneedle treatment

Transdermal delivery of drugs with microneedles: Strategies and outcomes

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