Microneedle-Assisted Percutaneous Delivery of Paeoniflorin-Loaded Ethosomes

Abstract

Paeoniflorin, the main component of total glucosides of paeony (TGP), shows good therapeutic effects in arthritis, but has low bioavailability when administered orally. Avoiding such a deficiency for topical administration would expand its clinical application. This study aimed to avoid these limitations by using nanotechnology (ethosomes) and a physical approach (microneedles). Paeoniflorin-loaded ethosomal formulation (TGP-E) was optimized and evaluated in terms of entrapment efficiency (EE), particle size (PS), zeta potential (ZP), polydispersity index (PDI) and morphology. TGP-E was prepared by the hot injection method and optimized by single-factor tests and an orthogonal experimental design. The optimized paeoniflorin-loaded ethosomes had EE of 27.82 ± 1.56%, PS of 137.9 ± 7.57 nm with PDI of 0.120 ± 0.005, ZP of −0.74 ± 0.43 mV. Ethosomes showed a nearly spherical shape under the transmission electron microscope (TEM). The optimal microneedle-assisted (MN-assisted) conditions were obtained at a microneedle length of 500 μm, a pressure of 3 N and an action time of 3 min. The cumulative penetration amounts (Qn) of TGP solution transdermal (ST) and MN-assisted TGP solution transdermal (MST) were 24.42 ± 8.35 μg/cm2 and 548.11 ± 10.49 μg/cm2, respectively. Qn of TGP-E transdermal (PT) and MN-assisted TGP-E transdermal (MPT) were 54.97 ± 4.72 μg/cm2 and 307.17 ± 26.36 μg/cm2, respectively. These findings indicate that use of ethosomes and microneedles can both enhance the penetration ofpaeoniflorin, but for the water-soluble drug, there is no obvious synergism between nanotechnology and microneedles for enhancing penetration in a transdermal drug delivery system.

Acid-Treated Water-Soluble Chitosan Suitable for Microneedle-Assisted Intracutaneous Drug Delivery

“…Recently, microneedle (MN)-assisted TDDSs have been widely investigated as they could create micron-sized holes, which provide a direct channel of mass transport regardless of drug type. Depending on the type of drug formulation and desired pharmacokinetic response in a body, numerous MN arrays had been fabricated in various sizes and geometries with diverse materials [19,20,21,22]. Although metal MNs prepared using silicon or ceramics can enhance the permeability of skin [23,24], complicate fabrication procedures employing conventional lithography, poor drug loading capacity, and health hazards arising from the breakage of these materials are limitations [25,26].…”

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics

“…However, this action depends on the particle size, MN-induced pore size, and the skin ability to recover. Compared with drug-loaded NPs, a small-molecule drug is expected to penetrate through the pores left by MNs in the skin [ 101 ]. Moreover, compared with micron-sized particles, drug-loaded NPs can more easily pass the skin barrier through the MN pores.…”

Optical Coherence Tomography and Microdialysis for Microneedle-Mediated Penetration Enhancement Study of Paeoniflorin-Loaded Ethosomes

“…Ex vivo skin permeation of TGP-S (or TGP-E) and MN-assisted TGP-S (or TGP-E) [14]: control condition and microneedletreated skin samples were fixed in the upper and lower chambers of a diffusion cell, with the dermis side facing the receptor compartment and the stratum corneum facing the donor compartment. The receiver compartment was filled with saline.…”

“…Theoretically, the combination of various methods to promote penetration should better promote the percutaneous absorption of drugs [13]. Ethosomes and microneedles are both relatively effective ways to promote penetration [14]. For topical preparations, crossing the skin barrier to corium is the premise that drugs can be absorbed into the systemic circulation by the capillaries spread to the dermis through diffusion and thus exert therapeutic effect [15].…”