TY - JOUR
T1 - Dissolving polymeric microneedle arrays for enhanced site-specific acyclovir delivery
AU - Pamornpathomkul, Boonnada
AU - Ngawhirunpat, Tanasait
AU - Tekko, Ismaiel A
AU - Vora, Lalitkumar
AU - McCarthy, Helen O
AU - Donnelly, Ryan F
N1 - Copyright © 2018 Elsevier B.V. All rights reserved.
PY - 2018/8/30
Y1 - 2018/8/30
N2 - Acyclovir is widely indicated for the treatment of herpes labialis (cold sores), typically caused by the herpes simplex virus type 1 (HSV-1). However, topical acyclovir has poor efficacy, due to its low skin permeability. The purpose of this study was, therefore, to evaluate the ability of dissolving polymeric microneedle (MN) arrays to improve the local delivery of acyclovir. Acyclovir-loaded dissolving MN arrays (0.49 cm2) were formulated from aqueous blends of Gantrez® S-97 with 361 needles per array (589 ± 9.29 μm height). MN penetrated excised neonatal porcine skin, showing sufficient mechanical strength to resist compression and maintained their appearance after application of a 0.089 N per needle force for 30 s. Dissolution of the needles was observed within 15 min after application to skin and the needles had completely dissolved at 2 h in vitro. In vitro skin permeation studies revealed that the percentage of total acyclovir loading which permeated the skin over a 24 h period using MNs was approximately 45 times higher than that of a commercial cream formulation (Lipsore®). The accumulation of acyclovir at the basal epidermis, the target site of the herpes simplex virus, using MNs was a total of 21.5 μg/cm3in vitro, which is approximately 5 times greater than the 99% inhibition of viral cytopathic effect (ID99) required for HSV infections. This level was also 16 times higher than that obtained using the cream formulation. An in vivo study showed that the use of acyclovir-loaded dissolving MN arrays successfully provided intradermal delivery of acyclovir over a 48 h period and the drug levels in the skin delivered using MN arrays (45.09 ± 13.28 μg/cm3) were superior to those generated by the cream formulation (4.55 ± 1.37 μg/cm3). Accordingly, acyclovir-loaded dissolving MN arrays could be a promising approach for effective local delivery of acyclovir.
AB - Acyclovir is widely indicated for the treatment of herpes labialis (cold sores), typically caused by the herpes simplex virus type 1 (HSV-1). However, topical acyclovir has poor efficacy, due to its low skin permeability. The purpose of this study was, therefore, to evaluate the ability of dissolving polymeric microneedle (MN) arrays to improve the local delivery of acyclovir. Acyclovir-loaded dissolving MN arrays (0.49 cm2) were formulated from aqueous blends of Gantrez® S-97 with 361 needles per array (589 ± 9.29 μm height). MN penetrated excised neonatal porcine skin, showing sufficient mechanical strength to resist compression and maintained their appearance after application of a 0.089 N per needle force for 30 s. Dissolution of the needles was observed within 15 min after application to skin and the needles had completely dissolved at 2 h in vitro. In vitro skin permeation studies revealed that the percentage of total acyclovir loading which permeated the skin over a 24 h period using MNs was approximately 45 times higher than that of a commercial cream formulation (Lipsore®). The accumulation of acyclovir at the basal epidermis, the target site of the herpes simplex virus, using MNs was a total of 21.5 μg/cm3in vitro, which is approximately 5 times greater than the 99% inhibition of viral cytopathic effect (ID99) required for HSV infections. This level was also 16 times higher than that obtained using the cream formulation. An in vivo study showed that the use of acyclovir-loaded dissolving MN arrays successfully provided intradermal delivery of acyclovir over a 48 h period and the drug levels in the skin delivered using MN arrays (45.09 ± 13.28 μg/cm3) were superior to those generated by the cream formulation (4.55 ± 1.37 μg/cm3). Accordingly, acyclovir-loaded dissolving MN arrays could be a promising approach for effective local delivery of acyclovir.
U2 - 10.1016/j.ejps.2018.05.009
DO - 10.1016/j.ejps.2018.05.009
M3 - Article
C2 - 29777854
SN - 0928-0987
VL - 121
SP - 200
EP - 209
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
ER -