Microporation Techniques for Enhanced Delivery of Therapeutic Agents

Abstract

Perhaps the greatest barrier to development of the field of transmembrane drug delivery is that only a limited number of drugs are amenable to administration by this route. The highly lipophilic nature and barrier function of the uppermost layer of the skin, the stratum corneum, for example, restricts the permeation of hydrophilic, high molecular weight and charged compounds into the systemic circulation. Other membranes in the human body can also present significant barriers to drug permeation. In order to successfully deliver hydrophilic drugs, and macromolecular agents of interest, including peptides, DNA and small interfering RNA, many research groups and pharmaceutical companies Worldwide are focusing on the use of microporation methods and devices. Whilst there are a variety of microporation techniques, including the use of laser, thermal ablation, electroporation, radiofrequency, ultrasound, high pressure jets, and microneedle technology, they share the common goal of enhancing the permeability of a biological membrane through the creation of transient aqueous transport pathways of micron dimensions across that membrane. Once created, these micropores are orders of magnitude larger than molecular dimensions and, therefore, should readily permit the transport of hydrophilic macromolecules. Additionally, microporation devices also enable minimally-invasive sampling and monitoring of biological fluids. This review deals with the innovations relating to microporation-based methods and devices for drug delivery and minimally invasive monitoring, as disclosed in recent patent literature.

Microneedle/nanoencapsulation-mediated transdermal delivery: Mechanistic insights

“…Dye solubility would affect the release and molecular diffusion steps of the hypothesized mechanism. Higher solubility was reported to increase drug flux across MN-treated skin since the dermis does not represent a distinct barrier to hydrophilic drugs once the SC is bypassed [45]. For instance, Stahl et al [46] demonstrated enhanced MN-driven permeation of the more hydrophilic permeants paracetamol and diclofenac compared to the lipophilic drugs ibuprofen and ketoprofen, irrespective of molecular weights.…”

Microneedles for drug delivery: trends and progress

“…The use of MN as a DD system is an important development as the potential to allow a wider scope of molecules to be transdermally delivered through the skin is greatly increased (Dhamech et al, 2010;Gittard et al, 2010;Milewski et al, 2010;Singh et al, 2010). The amount of drug that is delivered can also be increased.…”

Breaching the skin barrier through temperature modulations

“…RF-induced thermal ablation involves a mechanism that is somewhat similar to microporation, during which resistive heating is used. Devices are equipped with an array of micro-electrodes capable of generating an electric current into the skin in the radiofrequency range (100-500 kHz), thus inducing localised heating, liquid evaporation and the removal of cells [103,104]. This results in the creation of transient aqueous microchannels across the SC, which augment the transport of water soluble entities through the skin [103].…”

“…Devices are equipped with an array of micro-electrodes capable of generating an electric current into the skin in the radiofrequency range (100-500 kHz), thus inducing localised heating, liquid evaporation and the removal of cells [103,104]. This results in the creation of transient aqueous microchannels across the SC, which augment the transport of water soluble entities through the skin [103]. Transpharma Medical, which has now been acquired by Syneron Medical (Yokneam, Israel) developed the ViaDor® RF device (formerly known as ViaDerm®) (Fig.…”