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dcyphr | Temporal pressure enhanced topical drug delivery through micropore formation

Abstract

Administering a medication through the skin is called transdermal drug delivery (TDD). Currently, transdermal drug delivery is limited because not all drugs can penetrate through the skin. This study adds a pressure treatment to the skin, which increases micropores and gap junctions, while decreasing tight junctions. This means the skin is more permeable to the drug, and drugs like insulin can be given topically after a pressure treatment with an 80% efficient yield.

Aims

This study aims to make transdermal drug delivery (TDD) applicable to more drugs by including a pressure treatment before applying the drug to the skin.

Introduction

Transdermal drug delivery (TDD) is an easy, noninvasive method to administer drugs and can treat a variety of diseases. Since not all drugs are permeable to the skin, options like lasers, needles, pressure jets, and ultrasound waves are common ways to allow the drugs to enter the body. But these methods can be painful, risk infection, and require expensive machinery to complete. This study uses magnets to help alter the permeability of the skin and help drug delivery. The way this works is two magnets are placed so they pinch the target skin at a certain pressure for a certain amount of time. The magnets are removed and the drug is applied to the skin. This increased drug delivery in nanoparticles, dextran molecules, and insulin in mice. The optimized pressure and time is .28 MPa and 1-5 minutes.

Results and Methods

The TDD of the pressure treated skin was compared to the TDD of microneedling as a positive control, and no pressure treatment or microneedling as a negative control. Immunoassays and microscopy were used to visualize the absorption of the medications, as well as the altered skin environment after the pressure treatments and medication application. ELISA was used in the clinical application to see how much insulin entered the bloodstream after treatment.

 

Nanoparticles and Dextran Molecules

Nanoparticles and dextran molecules were used so that the research team could study how many different particle sizes were affected by the pressure treatment. In general, the smaller weight particles seemed to have better TDD after pressure treatments. Fluorescent nanoparticles were used so that the researchers could track the efficiency of TDD. For the nanoparticles, the pressure treatment worked as well as microneedling, and worked 9 fold better than normal skin. The pressure treatment also allowed the nanoparticles to be absorbed uniformly throughout the treated area, unlike the normal mouse skin, where the medication tended to be absorbed near follicles. 

 

There different pressures tested were .14, .28, and .40 MPa. The .14 pressure condition absorbed about 5 fold the normal condition, and the .28 and .40 conditions absorbed about 7 to 9 fold the normal condition. This makes it most favorable to use the .28 pressure because it maximized absorption while minimizing damage to the skin. 

 

When testing how long to apply pressure, it is clear that the longer the pressure is applied, the more TDD is able to successfully occur. 1 or 5 minute treatments were optimal.

 

Rabbit and pig skin were also tested in this study, and showed similar results in that the pressure treatment of .28 MPa increased TDD without damage to the skin.

 

Discussion

The safest and most effective pressure treatments were applying magnets for 1 or 5 minutes at .28 MPa, but these conditions could be created though any type of pressure generator, not necessarily magnets. These conditions were successful in mice, rabbit, and pig models. Diabetic mouse models showed that 10 fold concentrations of topical insulin, compared to the injected concentration, could be effective after 5 minute pressure treatments. This study also showed that insulin delivery through the pressure treated skin could be as time effective as the traditional injection or microneedling administrations.

 

The pressure treatment in this study is significantly safer, cheaper, and  less painful than some other methods that try to make TDD easier. The small micropore size formed after pressure treatment poses a significantly lower infection risk than needling techniques.

Further research should be done to optimize this exciting new therapy to human skin and drugs.

Conclusion

Treating the skin with pressure before applying topical drugs increases the transdermal drug delivery efficiency, and should be studied further to optimize human skin and drugs.