Lingxiao Xie

Transmucosal drug products, such as aerosols, films, semisolids, suppositories, and tablets, have been developed for the treatment of various human diseases and conditions. Transmucosal drug absorption is highly influenced by the biological structures of the mucosa and the physiological environment specific to the administration route (e.g., nasal, rectal, and vaginal). Over the last few decades, in vitro permeation testing (IVPT) using animal tissues or in vitro cell cultures have been utilized as a cost-effective and efficient tool for evaluating drug release and permeation behavior, assisting in formulation development and quality control of transmucosal drug delivery systems. This review summarizes the key mucosal permeation barriers associated with representative transmucosal administration routes, as well as considerations for IVPT method development. It highlights various IVPT methods, including vertical diffusion cell, flow-through diffusion cell, Ussing chamber, and transwell systems. Additionally, future perspectives are discussed, such as the use of optical methods to study in vitro drug permeation and the development of in vitro–in vivo correlation (IVIVC) for transmucosal drug development. The potential of IVPT as part of in vitro bioequivalence assessment strategies for locally acting transmucosal drug products is also highlighted.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults with high mortality. In order to improve prognosis and survival of UM patients, it is critical to inhibit tumor progression and metastasis as early as possible after the initial presentation/diagnosis of the disease. Sustained local delivery of antitumor therapeutics in the posterior region can potentially achieve long-term UM inhibition, improve target therapeutic delivery to the posterior segments, as well as reduce injection frequency and hence improved patient compliance. To address the highly unmet medical need in UM therapy, a bioinspired in situ gelling hydrogel system composed of naturally occurring biopolymers collagen and hyaluronic acid was developed in the present research. Curcumin with anti-cancer progression, anti-metastasis effects, and good ocular safety was chosen as the model therapeutic. The developed in situ gelling delivery system gelled at 37 °C within two minutes and demonstrated excellent biocompatibility and slow degradation. The curcumin-loaded nanoparticle/hydrogel composite was able to sustain release payload for up to four weeks. The optimized nanoparticle/hydrogel composite showed effective inhibition of human UM cell proliferation. This novel nanoparticle/in situ hydrogel composite demonstrated a great potential for the treatment of the rare and devastating intraocular cancer.