Rapid Sublingual Delivery of Piroxicam from Electrospun Cyclodextrin Inclusion Complex Nanofibers

Abstract

Piroxicam (Px) is a nonsteroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis and rheumatoid arthritis. It is administered orally; however, its poor water solubility causes low loading to the nonconventional drug delivery systems (DDSs), such as electrospun fibers. Furthermore, the rapid dissolution of DDS and fast release of the embedded drugs are crucial for oral delivery of drugs to patients who are unconscious or suffering from dysphagia. In this regard, this study reports the development of rapidly dissolving cyclodextrin (CD)-based inclusion complex (IC) nanofibers by waterborne electrospinning for fast oral delivery of Px. Scanning electron microscopy analysis revealed the formation of bead-free fibers with a mean diameter range of 170-500 nm at various concentrations of Px; increasing the Px loading decreased the fiber diameter. The formation of IC was demonstrated by X-ray diffraction (XRD) analysis by the disappearance of crystalline peaks of Px. Likewise, differential scanning calorimetry (DSC) analysis showed the disappearance of the melting peak of the embedded Px due to IC formation. Both Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) confirmed the presence of Px within the fibers. ¹H NMR experiments demonstrated Px preservation in the fibers after six months. Px-loaded nanofibers were employed for sublingual drug delivery. To mimic the environment of the mouth, the nanofibers were treated with artificial saliva, which revealed the instant dissolution of the nanofibers. Furthermore, dissolution experiments were performed on the tissues wetted with artificial saliva, where the dissolution of the fibers could be extended to a few seconds, demonstrating the suitability of the materials for sublingual oral drug delivery. Overall, this paper, for the first time, reports the rapid oral delivery of Px from polymer-free CD fibers produced by waterborne electrospinning without the requirement of any carrier polymer and toxic solvent.

Figure 1

(a) Chemical structures of HP-β-CD and Px and (b) a cartoon showing the inclusion complexation between the HP-β-CD and Px. (c) The production of nanofibers by waterborne electrospinning of IC solutions to be used for the sublingual delivery of Px.

Figure 2

(a) Optical photos of the HP-β-CD/Px mats prepared at various Px:HP-β-CD molar ratios ((i) 0.1:1; (ii) 0.25:1, (iii) 0.5:1, (iv) 1:1). (b) Photos of the Px:HP-β-CD mat (0.25:1) during folding many times.

Figure 3

Scanning electron microscopy images of HP-β-CD/Px nanofibers prepared at various Px:HP-β-CD molar ratios: (a) 0.1:1, (b) 0.25:1, (c) 0.5:1, and (d) 1:1. The bottom panel shows the size-distribution plots of the respective nanofibers.

Figure 4

(Left panel) FTIR spectra of the (a) Px powder, (b) HP-β-CD fibers, and (c–f) Px/HP-β-CD fibers ((c) 0.1:1, (d) 0.25:1, (e) 0.5:1, and (f) 1:1), and (right panel) displays the narrow range of the respective FTIR spectra of the materials.

Figure 5

Normalized TGA thermograms of the Px powder, HP-β-CD, and HP-β-CD/Px nanofibers of various molar ratios indicated.

Figure 6

DSC curves of the Px powder and HP-β-CD/Px fibers of various molar ratios.

Figure 7

Wide-angle XRD patterns of the (a) Px, (b) HP-β-CD fibers, and Px/HP-β-CD fibers of various molar ratios (c) 0.25:1, (d) 0.5:1, and (e) 1: 1, respectively.

Figure 8

¹H and ¹³C NMR spectra of the HP-β-CD fibers and HP-β-CD/Px fibers (1:0.5) in d₆-DMSO.

Figure 9

(A) The dissolution of the HP-β-CD/Px nanofibers prepared at various molar ratios (a) HP-β-CD control; (b) 0.25: 1 (Px: HP-β-CD); and (c) 0.5: 1 (Px: HP-β-CD) in artificial saliva. The photos were captured from Supporting Information Video 1. (B) Time-dependent in vitro release of Px from the HP-β-CD/Px nanofibers of different compositions in PBS (pH: 7.4).

Figure 10

Dissolution of the HP-β-CD (a) and Px/HP-β-CD nanofibers prepared at various molar ratios ((b) 0.1:1, (c) 0.25:1 and (d) 0.5:1 with respect to HP-β-CD) on tissues wetted with artificial saliva. The photos were captured from Supporting Information Video 2.