TY - JOUR

T1 - In vivo dermal delivery of bleomycin with electronic pneumatic injection

T2 - drug visualization and quantification with mass spectrometry

AU - Bik, Liora

AU - van Doorn, Martijn

AU - Hansen, Anders C. N.

AU - Janfelt, Christian

AU - Olesen, Uffe H.

AU - Haedersdal, Merete

AU - Lerche, Catharina M.

AU - Hendel, Kristoffer

PY - 2022

Y1 - 2022

N2 - Background Intralesional bleomycin (BLM) administration by needle injection is effective for keloids and warts but has significant drawbacks, including treatment-related pain and operator-depended success rates. Electronic pneumatic injection (EPI) is a promising, less painful, needle-free method that potentially enables precise and controlled dermal drug delivery. Here, we aimed to explore the cutaneous pharmacokinetics, biodistribution patterns, and tolerability of BLM administered by EPI in vivo. Research Design and Methods In a pig model, EPI with BLM or saline (SAL) were evaluated after 1, 48 and 216 hours. Mass spectrometry quantification and imaging were used to assess BLM concentrations and biodistribution patterns in skin biopsies. Tolerability was assessed by scoring local skin reactions (LSR) and measuring transepidermal water loss (TEWL). Results Directly after BLM injection a peak concentration of 109.2 mu g/cm(3) (43.9-175.2) was measured in skin biopsies. After 9 days BLM was undetectable. EPI resulted in a focal BLM biodistribution in the mid-dermal delivery zone resembling a triangular shape. Mild LSRs were resolved spontaneously and TEWL was unaffected. Conclusions BLM administered by EPI resulted in quantifiable and focal mid-dermal distribution of BLM. The high skin bioavailability holds a great potential for clinical effects and warrants further evaluation in future human studies.

AB - Background Intralesional bleomycin (BLM) administration by needle injection is effective for keloids and warts but has significant drawbacks, including treatment-related pain and operator-depended success rates. Electronic pneumatic injection (EPI) is a promising, less painful, needle-free method that potentially enables precise and controlled dermal drug delivery. Here, we aimed to explore the cutaneous pharmacokinetics, biodistribution patterns, and tolerability of BLM administered by EPI in vivo. Research Design and Methods In a pig model, EPI with BLM or saline (SAL) were evaluated after 1, 48 and 216 hours. Mass spectrometry quantification and imaging were used to assess BLM concentrations and biodistribution patterns in skin biopsies. Tolerability was assessed by scoring local skin reactions (LSR) and measuring transepidermal water loss (TEWL). Results Directly after BLM injection a peak concentration of 109.2 mu g/cm(3) (43.9-175.2) was measured in skin biopsies. After 9 days BLM was undetectable. EPI resulted in a focal BLM biodistribution in the mid-dermal delivery zone resembling a triangular shape. Mild LSRs were resolved spontaneously and TEWL was unaffected. Conclusions BLM administered by EPI resulted in quantifiable and focal mid-dermal distribution of BLM. The high skin bioavailability holds a great potential for clinical effects and warrants further evaluation in future human studies.

KW - Bleomycin

KW - drug delivery

KW - LC-MS

KW - MALDI

KW - needle-free injection

KW - skin

KW - ASSISTED TOPICAL DELIVERY

KW - FRACTIONAL LASER

U2 - 10.1080/17425247.2022.2035719

DO - 10.1080/17425247.2022.2035719

M3 - Journal article

C2 - 35107046

VL - 19

SP - 213

EP - 219

JO - Expert Opinion on Drug Delivery

JF - Expert Opinion on Drug Delivery

SN - 1742-5247

IS - 2

ER -