Mayes S, Ferrone M. Abstract Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. Clinical evaluation of a continuous minimally invasive glucose flux sensor placed over ultrasonically permeated skin. Comparison of transdermal delivery systems In addition to more than drugs formulated as creams and ointments, there are now 19 drugs or drug combinations administered using FDA-approved transdermal delivery systems Fig. Transdermal protein delivery by a coadministered peptide identified via phage display.
Recently, peptides have been examined as enhancers of skin permeability. The magainin was only effective when used in synergistic combination with a surfactant chemical enhancer, which served the dual purpose of increasing skin permeability to the drug as well as increasing penetration of magainin into the stratum corneum. Although vaccines are typically macromolecules, viral particles, or other large supramolecular constructs, their small microgram doses facilitate the possibility of transdermal delivery. Using Fourier transform infrared FTIR spectroscopy as a screening tool, they proposed that effective and non-irritating enhancers should alter stratum corneum lipid CH2 symmetric stretching which correlates with increased skin permeability and avoid changes in stratum corneum protein amide I band absorption which correlates with skin irritation. Table of Contents Alerts.
Conventional chemical enhancers Recognizing the need to increase skin permeability, second-generation delivery strategies have turned largely to the development of chemical enhancers 11 The effect of heat on skin permeability.
Weniger BG, Papania M.
Practical considerations for optimal transdermal drug delivery.
The oral route of medication is usually not suited and parenteral therapy has various limitations and drawbacks. A recently approved iontophoretic patch enables patients to periodically activate the patch to administer literzture bolus of fentanyl based on their need for pain relief 8 Table 1.
Bull World Health Organ. Noninvasive and minimally invasive methods for transdermal glucose monitoring.
Induction of cytotoxic T-lymphocytes by electroporation-enhanced needle-free skin immunization. A transdermal patch TP is a ltierature patch that is placed on skin for delivery of medication through skin into the blood stream.
In addition, transdermal systems are non-invasive and can be self-administered. A small subset of these enhancers that increase skin permeability without irritation have been used successfully to deliver small molecules, but have had limited impact on the problem of delivering hydrophilic compounds or macromolecules.
Excitement about this approach is exemplified by completion of phase 3 clinical trails and submission for registration in Europe by Sanofi Pasteur Paris and Becton Dickinson Franklin Lakes, NJ, USA for their microneedle-based influenza vaccine Table 2 ; major investments in Iomai for their transdermal vaccine patch portfolio; and a growing number of academic and industry laboratories engaging in this field of research.
In addition to recommendations on the site and duration of TDDS application and proper patch disposal, clinicians must consider 1 potential problems with cutting patches as a method of dosage adjustment, 2 safety concerns related to the electric conductivity of metal-containing patches, 3 appropriate strategies for managing patch adhesion failures, and 4 the advisability of writing on patches for medication safety or compliance reasons.
The magainin was only effective when used in synergistic combination with a surfactant chemical enhancer, which served the dual purpose of increasing skin permeability to the drug as well as increasing penetration of magainin into the stratum corneum.
In conventional medicine, the antiemetic treatment comes along with certain side effects. Nat Rev Drug Discov. Under different conditions, ultrasound can also be used to generate cavitational bubble activity, which has different effects and is discussed below.
Transdermal drug delivery
These methods have special promise, because they appear broadly capable of delivering not only small molecules, but macromolecules and vaccines as well.
The TDDS can deliver certain medications to systemic circulation in a more convenient and effective way than conventional dosage form.
Over the past 5 years —that rate has more than tripled to a new transdermal delivery system every 7. The microscopic length scales of localized skin disruption caused by thermal ablation have resulted in the procedure being well tolerated.
However, microneedles are also unique in that they are physically invasive, which raises additional safety and sterility considerations. After applying a naltrexone patch, blood levels of naltrexone reached the therapeutic range. Vaccine delivery using microneedles has also been a focus for research. Such a study was carried out, examining close to different pairs literahure chemical enhancers formulated to have more than compositions Chaturvedula A, et al. Significant advances in patch technology, and public acceptance, have enabled the recent surge in first-generation transdermal patches reaching the market Box 2.
Microneedles A conceptually straightforward way to selectively permeabilize the stratum corneum is to pierce it with very short needles. The associated pain and muscle stimulation can be avoided by using closely spaced microelectrodes that constrain the electric field within the stratum corneum These designs characteristically are composed of four layers: The various chemical enhancers can be integrated into small, inexpensive patches that patients find convenient.
Thermal ablation Thermal ablation selectively heats the skin surface to generate micron-scale perforations in the stratum corneum. Enhancement of transdermal delivery of 6-beta-naltrexol via a codrug linked to hydroxybupropion. The plot is shown in Figure 1. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. Although effective, applications of cavitational ultrasound may be limited by the need for a sophisticated device that only increases skin permeability at the nanometer scale and thereby may not be broadly applicable to macromolecules and vaccines.
Likewise, non-cavitational ultrasound has found use for transdermal delivery of anti-inflammatories in the context of physical therapy, but does not appear suitable for delivery of large compounds.