Berberine hydrochloride-loaded liposomes-in-hydrogel microneedles achieve the efficient treatment for psoriasis

Abstract

Psoriasis is a common immune-mediated squamous skin disease, primarily characterized by the over proliferation of keratinocytes and a significant thickening of the stratum corneum. Traditional systemic drug delivery therapies often fall short due to low drug bioavailability and significant toxic side effects. Topical medications, while capable of achieving local or systemic treatment via transdermal routes, face limitations in psoriasis patients due to the abnormal thickening of the epidermis, which reduces skin permeability and hampers drug penetration efficiency. Hydrogel microneedles, as an emerging transdermal drug delivery technology, offer significant advantages such as high permeability, ease of use, low toxicity and side effects, and controlled release. Therefore, this study developed a liposome-hydrogel microneedle delivery system for the administration of berberine hydrochloride. We successfully prepared berberine hydrochloride-loaded liposomes (Ber-LPs) with high encapsulation efficiency and good stability, and integrated them into hydrogel microneedles crosslinked with PVA and PEGDA (Ber-LPs-PEGDA&PVA MNs) through a photocuring method. These microneedles exhibit an intact structure, high mechanical strength, and effective skin penetration. In vivo studies on anti-psoriatic effects showed that, compared to the model group, Ber-LPs-PEGDA&PVA MNs significantly alleviated imiquimod-induced psoriasis-like symptoms in mice, reduced skin epidermal thickness, decreased the expression levels of inflammatory cytokines, and lowered the expression of CD31 and VEGF, demonstrating excellent therapeutic efficacy. Additionally, the microneedles exhibited good drug release properties, antioxidant capacity, and biocompatibility. The novel hydrogel microneedle drug delivery system developed in this study offers a safe and effective solution for the treatment of psoriasis, with significant potential for clinical application.

Keywords: Antioxidant; Hydrogel microneedles; Inflammatory skin diseases; Liposomes; Psoriasis.

Graphical abstract

Fig. 1

Preparation and characterization of Ber-LPs. (A) Schematic Diagram of the Preparation Process of Ber-LPs. (B) TEM Image of Ber-LPs. (C) Particle Size Distribution of Ber-LPs. (D) Zeta Potential Graph of Ber-LPs. (E) Response Surface Optimization Design for the Preparation of Ber-LPs.

Fig. 2

Preparation and characterization of MNs. (A) Schematic diagram for the preparation of Ber-LPs-PEGDA&PVA MNs arrays. (B) The design of MNs body. (C) Infrared spectra of PEGDA, PVA, and PEGDA&PVA. (D) Schematic diagram of the texture analyzer test for the mechanical properties of MNs. (E) Mechanical strength of PEGDA&PVA MNs and PEGDA MNs. (F) Digital camera images of Ber-LPs-PEGDA&PVA MNs. (G) The THUNDER images of Ber-LPs-PEGDA&PVA MNs. (H) SEM side view of PEGDA&PVA MNs. (I) SEM top view of PEGDA&PVA MNs. (J) SEM side view of PEGDA MNs. (K) SEM top view of PEGDA MNs.

Fig. 3

The formation process of PEGDA&PVA interpenetrating polymer networks.

Fig. 4

In vitro experiments of MNs. (A) Franz diffusion cell diagram for transdermal diffusion. (B) Cumulative release curve per unit area (mean ± SD, n = 3). (C) Skin recovery status after application of Ber-LPs-PEGDA&PVA MNs. (D) H&E staining of skin biopsy sections after application of Ber-LPs-PEGDA&PVA MNs. (E) Scavenging rates of DPPH and ABTS (F) by Ber-LPs-PEGDA&PVA MNs at different concentrations. (G) Hemolysis rates of extracts from Ber-LPs-PEGDA&PVA MNs at different concentrations; inset shows images of the hemolysis test. (H) Cell viability of L929 cells after incubation with extracts from Ber-LPs-PEGDA&PVA MNs for 24 h and 48 h at different concentrations. Data are presented as mean ± SD, n = 3, ∗p < 0.05, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001, ns > 0.05.

Fig. 5

Therapeutic effects of different groups on psoriasis models. (A) Schematic diagram of the establishment and treatment of the IMQ-induced psoriasis model. (B) Photographs of the dorsal skin of mice treated with different groups. (C) H&E staining of mouse skin sections. (D) Changes in body weight during treatment. (E) Epidermal thickness of the skin measured from skin sections. Data are presented as mean ± SD (n = 5), with ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001 indicating statistical significance.

Fig. 6

Therapeutic effects of different groups on psoriasis models. (A) Spleen index. (B) Digital images of the spleen. (C) Positive expression rate of CD31 in mouse skin sections. (D) Positive expression rate of VEGF in mouse skin sections. (E) Immunohistochemical micrographs of CD31 and VEGF in mouse skin sections. (F) Expression levels of IFN-γ, TNF-α, IL-17, and IL-23 in the serum of psoriasis mice from different formulation groups. (G) Expression levels of CAT, GSH-Px, MDA, and SOD in the skin tissues of psoriasis mice from different formulation groups. Data are presented as mean ± SD (n = 5), Data are presented as mean ± SD, n = 3, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001, ns > 0.05.