Skin pre-ablation and laser assisted microjet injection for deep tissue penetration.

Abstract

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. 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. 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). 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.