Skin pre‐ablation and laser assisted microjet injection for deep tissue penetration
Authors: Jang Hun‐Jae , Yeo Seonggu , Yoh Jack J. 
Published: October 2016

Background and Aims

For conventional needless injection, there still remain many unresolved issues such as the potential for cross‐contamination, poor reliability of targeted delivery dose, and significantly painstaking procedures. As an alternative, the use of microjets generated with Er:YAG laser for delivering small doses with controlled penetration depths has been reported. In this study, a new system with two stages is evaluated for effective transdermal drug delivery. First, the skin is pre‐ablated to eliminate the hard outer layer and second, laser‐driven microjet penetrates the relatively weaker and freshly exposed epidermis. Each stage of operation shares a single Er:YAG laser that is suitable for skin ablation as well as for the generation of a microjet.

Methods

In this study, pig skin is selected for quantification of the injection depth based on the two‐stage procedure, namely pre‐ablation and microjet injection. The three types of pre‐ablation devised here consists of bulk ablation, fractional ablation, and fractional–rotational ablation. The number of laser pulses are 12, 18, and 24 for each ablation type. For fractional–rotational ablation, the fractional beams are rotated by 11.25° at each pulse. The drug permeation in the skin is evaluated using tissue marking dyes. The depth of penetration is quantified by a cross sectional view of the single spot injections. Multi‐spot injections are also carried out to control the dose and spread of the drug.

Results

The benefits of a pre‐ablation procedure prior to the actual microjet injection to the penetration is verified. The four possible combinations of injection are (a) microjet only; (b) bulk ablation and microjet injection; (c) fractional ablation and microjet injection; and (d) fractional‐rotational ablation and microjet injection. Accordingly, the total depth increases with injection time for all cases. In particular, the total depth of penetration attained via fractional pre‐ablation increased by 8 ∼ 11% and that of fractional–rotational pre‐ablation increased by 13 ∼ 33%, when compared with the no pre‐ablation or microjet only cases. A noticeable point is that the fraction‐rotational pre‐ablation and microjet result is comparable to the bulk ablation and microjet result of 11 ∼ 42%. The penetration depth underneath ablated stratum corneum (SC) is also measured in order to verify the pre‐ablation effect. The penetration depths for each case are (a) 443  104 µm; (b) 625  98 µm; (c) 523  95 µm; and (d) 595  141 µm for microjet only, bulk ablation and microjet, fractional ablation and microjet, and fractional–rotational ablation and microjet, respectively. This is quite beneficial since any healing time associated with ablation is significantly reduced by avoiding hard‐core bulk ablation. Thus the bulk pre‐ablation and microjet may well be superseded by the less invasive fractiona–rotational ablation followed by the microjet injection. The density of micro‐holes is 1.27 number/mm2 for fractional ablation and 4.84 number/mm2 for fractional–rotational ablation. The penetration depths measured underneath the ablated SC are 581 µm (fractional ablation and microjet) and 691 µm (fractional–rotational ablation and microjet).

Conclusions

Fractional–rotational ablation increases number of micro‐holes in a unit area, enabling fast reepithelialization and high drug delivery efficiency. Optimization of system parameters such as ablation time, number of ablations, and injection time will eventually ensure a macromolecule delivery technique with the potential to include vaccines, insulins, and growth hormones, all of which require deeper penetration into the skin. Lasers Surg. Med. 49:387–394, 2017. © 2016 Wiley Periodicals, Inc.