Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections

Abstract

Chronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability. Microneedles (MNs) are emerging as a minimally invasive method to enhance ocular drug delivery. This study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)–based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays’ reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MN arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch. Graphical abstract

Optimal Design of Novel Microemulsions-Based Two-Layered Dissolving Microneedles for Delivering Fluconazole in Treatment of Fungal Eye Infection

“…The mechanical strengths of two-layered dissolving MNs with and without FLUZ were 21.57 N ± 1.04 and 20.85 ± 1.09 N, respectively, indicating that FLUZ loaded into the inner layer (1.27% w / w ) did not significantly change the mechanical strength of the two-layered dissolving MNs. To completely insert into the cornea (600 µm thick), the estimated insertion forces were 5.70 ± 0.51 N/121 array or 0.05 N per needle in control and 5.18 ± 0.49 N/121 array or 0.04 N per needle in optimal formulation ( Figure 5 B), referring to the appropriate insertion forces to use as an ocular device patch (0.05–0.15 N) with minimally invasive corneal tissue [ 22 , 37 , 38 ].…”

“…The ability of FLUZ-MEs-loaded two-layered dissolving MNs to complete insertion on corneal tissue was tested on the artificial membrane polymeric film (Parafilm M ® ; Bemis NA, Neenah, WI, USA). This MN array was placed on the 5 layers of polymeric film (mimics the corneal thickness around 650 µm) [ 37 ] and then used the insertion force from the previous study for 30 s. The number of visible dots on the polymeric film surface were counted under a Dino-Lite digital microscope (Hsinchu, Taiwan). The insertion ability of the MNs was calculated by the following Equation (3).…”

“…To evaluate the depth of insertion, the artificial membranes from the previous study were removed from each artificial membrane layer and the last remaining visible dot under a digital microscope was observed to calculate the depth. Each artificial membrane layer’s thickness is 0.13 mm [ 37 ]. Moreover, the fluorescein-sodium-loaded two-layered MNs were applied on the porcine corneal tissue for 3 min.…”

Recent Advancements in Microneedle Technology for Multifaceted Biomedical Applications

“…Moreover, it was found that AMP-B-loaded dissolving MNs showed significant antifungal activity compared to plain drugs. Furthermore, MNs maintain the activity of drugs [ 222 ].…”

Dissolving microneedle patches loaded with amphotericin B microparticles for localised and sustained intradermal delivery: Potential for enhanced treatment of cutaneous fungal infections

“…Various formulations for AmB DMP were prepared using aqueous blends of PVA and PVP as matrices. PVP and PVA were chosen because they are both safe [49,50], and can form mechanically strong DMP to deliver hydrophobic drugs, as demonstrated by several studies [18,[51][52][53][54]. Furthermore, AmB and PVP complexes exhibited comparable antifungal effects to AmB with less toxicity [54].…”