Fluorinated Polymer Mediated Transmucosal Peptide Delivery for Intravesical Instillation Therapy of Bladder Cancer.

Surgical intervention combined with intravesical instillation of chemotherapeutics to clear residual cancer cells after operation is the current standard treatment method for bladder cancer. However, the poor bioavailability of active pharmaceutical ingredients for bladder cancer cells on account of the biological barriers of bladder mucosa, together with significant side effects of currently used intravesical medicine, have limited the clinical outcomes of localized adjuvant therapy for bladder cancer. Aiming at improved intravesical instillation therapy of bladder cancer, a fluorinated polyethylenimine (F-PEI) is employed here for the transmucosal delivery of an active venom peptide, polybia-mastoparan I (MPI), which shows selective antiproliferative effect against various bladder cancer cell lines. Upon simple mixing, MPI and F-PET would coassemble to form stable nanoparticles, which show greatly improved cross-membrane and transmucosal penetration capacities compared with MPI alone or nonfluorinated MPI/PEI nanoparticles. MPI/F-PEI shows higher in vivo tumor growth inhibition efficacy for local treatment of a subcutaneous tumor model. More excitingly, as further demonstrated in an orthotopic bladder cancer model, MPI/F-PEI offers remarkably improved therapeutic effects compared to those achieved by free MPI or the first-line bladder cancer drug mitomycin C. This work presents a new transmucosal delivery carrier particularly promising for intravesical instillation therapy of bladder cancer.

Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy.

OBJECTIVE: The aim of this work was the development of mucoadhesive sublingual films, prepared using a casting method, for the administration of oxycodone. MATERIALS AND METHODS: A solvent casting method was employed to prepare the mucoadhesive films. A calibrated pipette was used to deposit single aliquots of different polymeric solutions on a polystyrene plate lid. Among the various tested polymers, hydroxypropylcellulose at low and medium molecular weight (HPC) and pectin at two different degrees of esterification (PC) were chosen for preparing solutions with good casting properties, capable of producing films suitable for mucosal application. RESULTS AND DISCUSSION: The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8 min, ranged from 60% to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction in elasticity has been observed in films containing a higher drug dose; nevertheless, the formulation maintained satisfactory flexibility and resistance to elongation. CONCLUSIONS: HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues.

Mucus is a viscoelastic gel layer that typically protects exposed surfaces of the gastrointestinal (GI) tract, lung airways, and other mucosal tissues. Particles targeted to these tissues can be efficiently trapped and removed by mucus, thereby limiting the effectiveness of such drug delivery systems. In this study, we experimentally and theoretically demonstrated that cylindrical nanoparticles (NPs), such as mesoporous silica nanorods and calcium phosphate nanorods, have superior transport and trafficking capability in mucus compared with spheres of the same chemistry. The higher diffusivity of nanorods leads to deeper mucus penetration and a longer retention time in the GI tract than that of their spherical counterparts. Molecular simulations and stimulated emission of depletion (STED) microscopy revealed that this anomalous phenomenon can be attributed to the rotational dynamics of the NPs facilitated by the mucin fibers and the shear flow. These findings shed new light on the shape design of NP-based drug delivery systems targeted to mucosal and tumor sites that possess a fibrous structure/porous medium.

Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers.

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.

Exploring Mechanisms of Lipid Nanoparticle-Mucus Interactions in Healthy and Cystic Fibrosis Conditions.

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerge as versatile non-viral gene delivery systems that can help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics (BD) simulations. Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery.

Cell-penetrating peptides for transmucosal delivery of proteins.

Enabling non-invasive delivery of proteins across the mucosal barriers promises improved patient compliance and therapeutic efficacies. Cell-penetrating peptides (CPPs) are emerging as a promising and versatile tool to enhance protein and peptide permeation across various mucosal barriers. This review examines the structural and physicochemical attributes of the nasal, buccal, sublingual, and oral mucosa that hamper macromolecular delivery. Recent development of CPPs for overcoming those mucosal barriers for protein delivery is summarized and analyzed. Perspectives regarding current challenges and future research directions towards improving non-invasive transmucosal delivery of macromolecules for ultimate clinical translation are discussed.

Inhalable metal-organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy.

Cuproptosis shows enormous application prospects in lung metastasis treatment. However, the glycolysis, Cu+ efflux mechanisms, and insufficient lung drug accumulation severely restrict cuproptosis efficacy. Herein, an inhalable poly (2-(N-oxide-N,N-diethylamino)ethyl methacrylate) (OPDEA)-coated copper-based metal-organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA (siPDK) is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy, namely OMP. After inhalation, OMP shows highly efficient lung accumulation and long-term retention, ascribing to the OPDEA-mediated pulmonary mucosa penetration. Within tumor cells, OMP is degraded to release Cu2+ under acidic condition, which will be reduced to toxic Cu+ to induce cuproptosis under glutathione (GSH) regulation. Meanwhile, siPDK released from OMP inhibits intracellular glycolysis and adenosine-5'-triphosphate (ATP) production, then blocking the Cu+ efflux protein ATP7B, thereby rendering tumor cells more sensitive to OMP-mediated cuproptosis. Moreover, OMP-mediated cuproptosis triggers immunogenic cell death (ICD) to promote dendritic cells (DCs) maturation and CD8+ T cells infiltration. Notably, OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1 (PD-L1) expression and induces soluble PD-L1 secretion, and thus synergizes with anti-PD-L1 antibodies (aPD-L1) to reprogram immunosuppressive tumor microenvironment, finally yielding improved immunotherapy efficacy. Overall, OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1.

Novel Double-Layer Dissolving Microneedles for Transmucosal Sequential Delivery of Multiple Drugs in the Treatment of Oral Mucosa Diseases.

The development of transmucosal drug delivery systems is a practical requirement in oral clinical practice, and controlled sequential delivery of multiple drugs is usually required. On the basis of the previous successful construction of monolayer microneedles (MNs) for transmucosal drug delivery, we designed transmucosal double-layer sequential dissolving MNs using hyaluronic acid methacryloyl (HAMA), hyaluronic acid (HA), and polyvinyl pyrrolidone (PVP). MNs have the advantages of small size, easy operation, good strength, rapid dissolution, and one-time delivery of two drugs. Morphological test results showed that the HAMA-HA-PVP MNs were small and intact in structure. The mechanical strength and mucosal insertion test results indicated the HAMA-HA-PVP MNs had appropriate strength and could penetrate the mucosal cuticle quickly to achieve transmucosal drug delivery. The in vitro and in vivo experiment results of the double-layer fluorescent dyes simulating drug release revealed that MNs had good solubility and achieved stratified release of the model drugs. The results of the in vivo and in vitro biosafety tests also indicated that the HAMA-HA-PVP MNs were biosafe materials. The therapeutic effect of drug-loaded HAMA-HA-PVP MNs in the rat oral mucosal ulcer model demonstrated that these novel HAMA-HA-PVP MNs quickly penetrated the mucosa, dissolved and effectively released the drug, and achieved sequential drug delivery. Compared to monolayer MNs, these HAMA-HA-PVP MNs can be used as double-layer drug reservoirs for controlled release, effectively releasing the drug in the MN stratification by dissolution in the presence of moisture. The need for secondary or multiple injections can be avoided, thus improving patient compliance. This drug delivery system can serve as an efficient, multipermeable, mucosal, and needle-free alternative for biomedical applications.

Inhalable pH-responsive DNA tetrahedron nanoplatform for boosting anti-tumor immune responses against metastatic lung cancer.

Despite advancements in the treatment of pulmonary cancer, the existence of mucosal barriers in lung still hampered the penetration and diffusion of therapeutic agents and greatly limited the therapeutic benefits. In this work, we reported a novel inhalable pH-responsive tetrahedral DNA nanomachines with simultaneous delivery of immunomodulatory CpG oligonucleotide and PD-L1-targeting antagonistic DNA aptamer (CP@TDN) for efficient treatment of pulmonary metastatic cancer. By precisely controlling the ratios of CpG and PD-L1 aptamer, the obtained CP@TDN could specifically release PD-L1 aptamer to block PD-1/PD-L1 immune checkpoint axis in acidic tumor microenvironment, followed by endocytosis by antigen-presenting cells to generate anti-tumor immune activation and secretion of anti-tumor cytokines. Moreover, inhalation delivery of CP@TDN showed highly-efficient lung deposition with greatly enhanced intratumoral accumulation, ascribing to the DNA tetrahedron-mediated penetration of pulmonary mucosa. Resultantly, CP@TDN could significantly inhibit the growth of metastatic orthotopic lung tumors via the induction of robust antitumor responses. Therefore, our work presents an attractive approach by virtue of biocompatible DNA tetrahedron as the inhalation delivery system for effective treatment of metastatic lung cancer.

Protamine-mediated efficient transcellular and transmucosal delivery of proteins.

Proteins and peptides often require frequent needle-based administrations. Here, we report a non-parenteral delivery method for proteins through physical mixing with protamine, an FDA-approved peptide. Protamine was shown to promote tubulation and rearrangement of cellular actin, leading to enhanced intracellular delivery of proteins compared to poly(arginine)8 (R8). While the R8-mediated delivery resulted in significant lysosomal accumulation of the cargo, protamine directed the proteins to the nuclei with little lysosomal uptake. Intranasal delivery of insulin mixed with protamine effectively reduced blood glucose levels in diabetic mice 0.5 h after administration and the effect lasted for ∼6 h, comparable to subcutaneously injected insulin at the same dose. In mice, protamine was shown to overcome mucosal and epithelial barriers and modulate adherens junctions, promoting insulin penetration to the lamina propria layer for systemic absorption.

Three-Dimensional Oral Mucosal Equivalents as Models for Transmucosal Drug Permeation Studies.

Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm2/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4-5 cell layers with basal cells still undergoing mitosis. The optimum period at the air-liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca2+, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes' differentiation and inflammatory conditions, etc.).

Ethosomal gel for rectal transmucosal delivery of domperidone: design of experiment, in vitro, and in vivo evaluation.

Despite high efficiency of domperidone (DOM) in prophylaxis of emesis accompanied with radiotherapy and chemotherapy, it still can bother cancer patients by its powerful side effects and difficulty of its oral administration. The study was designed to develop and optimize DOM loaded ethosomal gel for rectal transmucosal delivery. Ethosomal formulations were prepared using a 21, 51 full-factorial design where the impact of lecithin concentration and additives were investigated. The optimum ethosomal vesicles were subsequently incorporated in Carbopol gel base where rheological behavior, spreadability, mucoadhesion, and in vivo pharmacokinetic parameters were studied. Based on Design Expert® software (Stat Ease, Inc., Minneapolis, MN), the optimum formulation illustrated entrapment efficiency of 70.02%±5.52%, and vesicular size of 112 ± 3.3 nm, polydispersity index of 0.32 ± 0.01, zeta potential of -59 ± 0.28 mV, and % drug released after 6 h of 76.30%±2.45%. Moreover, ex vivo permeation through rabbit intestinal mucosa increased four times compared to free DOM suspension. The gel loaded with ethosomes showed excellent mucoadhesion to rectal mucosa. DOM ethosomal gel showed a raise in Cmax and AUC0-48 of DOM by twofolds compared to free DOM gel. The study suggested that ethosomes incorporated in gels could be an efficient candidate for rectal transmucosal delivery of DOM.

Synthesis of Methacryloylated Hydroxyethylcellulose and Development of Mucoadhesive Wafers for Buccal Drug Delivery.

Non-ionic hydroxyethylcellulose (HEC) has limited mucoadhesive properties for application in transmucosal drug delivery. In this study, HEC was chemically modified by reaction with glycidyl methacrylate. This allowed introducing the methacryloyl groups to HEC structure to make it capable of forming covalent bonds with the sulfhydryl groups present in the mucin glycoprotein to achieve enhanced mucoadhesive properties. The results showed a successful modification of HEC as confirmed by 1H NMR and FTIR spectroscopies. The quantification of methacryloyl moieties was conducted using HPLC. The toxicity studies using in vivo planaria acute toxicity assay, in vivo planaria fluorescent test, and in vitro MTT assay with Caco-2 cell line confirmed that the chemical modification of HEC does not result in any toxicological effects. Mucoadhesive wafers were developed based on parent and modified HEC as a model dosage form for buccal delivery. The mucoadhesive properties of modified HEC assessed using a tensile test were found to be significantly better compared to unmodified HEC.

Development of a Mucoadhesive Vehicle Based on Lyophilized Liposomes for Drug Delivery through the Sublingual Mucosa.

A pharmaceutical vehicle based on lyophilized liposomes is proposed for the buccal administration of drugs aimed at systemic delivery through the sublingual mucosa. Liposomes made of egg phosphatidylcholine and cholesterol (7/3 molar ratio) were prepared and lyophilized in the presence of different additive mixtures with mucoadhesive and taste-masking properties. Palatability was assayed on healthy volunteers. The lyophilization cycle was optimized, and the lyophilized product was compressed to obtain round and capsule-shaped tables that were evaluated in healthy volunteers. Tablets were also assayed regarding weight and thickness uniformities, swelling index and liposome release. The results proved that lyophilized liposomes in unidirectional round tablets have palatability, small size, comfortability and buccal retention adequate for sublingual administration. In contact with water fluids, the tablets swelled, and rehydrated liposomes were released at a slower rate than permeation efficiency determined using a biomimetic membrane. Permeability efficiency values of 0.72 ± 0.34 µg/cm2/min and 4.18 ± 0.95 µg/cm2/min were obtained for the liposomes with and without additives, respectively. Altogether, the results point to the vehicle proposed as a liposomal formulation suitable for systemic drug delivery through the sublingual mucosa.

In vitro and in vivo evaluation of 3D printed sodium alginate/polyethylene glycol scaffolds for sublingual delivery of insulin: Preparation, characterization, and pharmacokinetics.

Delivery of therapeutic peptides via sublingual administration is extremely desired and 3D printed scaffolds are potential candidates as carriers to enhance insulin delivery. 3D printed sublingual sodium alginate (SA)/polyethylene glycol (PEG) composite scaffolds were produced for enhancing insulin delivery by examining the chemical, morphological, mechanical, thermal, cytotoxic, and pharmacokinetic features. The tensile strength and flexibility of scaffolds increased after loading insulin due to the crystalline structure of insulin. Furthermore, insulin-loaded 9SA/3PEG scaffolds showed ultrafast wetting (<1 s), disintegration (<6 s), and also dissolution (<30 s) according to Hixson-Crowell kinetic model. The cell viability of L929 cells on 3D printed scaffolds was examined and these scaffolds could be safely applied on animals. Pharmacokinetic parameters and blood glucose level were evaluated following sublingual administration of scaffolds to type-1 diabetic rats. A single dose of scaffold presented a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min and it lasted for 12 h by increasing the bioavailability of insulin. Scaffolds indicated a sustained profile for serum insulin levels, which continued to increase slightly after 3 h during the study. The polymeric scaffold with a high safety and efficacy holds a new promising delivery strategy for administering injectable insulin through the sublingual route.

Oral transmucosal delivery of eletriptan for neurological diseases.

Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.

Ovalbumin and cholera toxin delivery to buccal mucus for immunization using microneedles and comparison of immunological response to transmucosal delivery.

The oral mucosa is an effective site for vaccination. However, for oral mucosal vaccines, delivery of the right dose of vaccine is not possible due to the water-rich environment. In this study, the buccal mucosa, which is easy to access using a microneedle array in the oral cavity, was selected as the administration site. The immune responses to the use of microneedles to conventional transmucosal delivery were compared. In addition, the adjuvant effect of the addition of cholera toxin (CT) to the drug formulation was observed. Two kinds of patches were prepared: (1) Ovalbumin (OVA) was dip coated only on the tips of microneedles (C-OVA-MN) and (2) OVA was coated on the surface of a flat disk patch substrate without microneedles (C-OVA-D). The drug delivery properties of C-OVA-MN and C-OVA-D were investigated using fluorescent-labeled OVA (OVA/FITC). Each patch was administered to mice twice, 2 weeks apart, and then antibody titers were measured. A microneedle patch can deliver vaccine into the epithelium of the buccal mucosa in a short period of time compared to transmucosal delivery. A microneedle system of C-OVA-MN showed a high serum IgG titer. In addition, CT triggered CD8+ and CD4+ T cell-mediated immune responses. Through this study, we present the possibility of a new method of vaccination to the buccal mucosa using microneedles and CT adjuvant. Illustration of delivery of vaccine to the oral mucosal epithelium using a microneedle patch: Ovalbumin (OVA)-coated microneedle (C-OVA-MN) consists of tip, step, and coating formulation. Microneedle patch coated with OVA formulation is targeting buccal mucosa, which is easy to access in the oral cavity. OVA is delivered to the buccal epithelium precisely using a microneedle patch, and OVA is delivered by transmucosal route using a disk patch.

Transmucosal Delivery of Self-Assembling Photosensitizer-Nitazoxanide Nanocomplexes with Fluorinated Chitosan for Instillation-Based Photodynamic Therapy of Orthotopic Bladder Tumors.

Theoretically, on account of improved local bioavailability of photosensitizers and attenuated systemic phototoxicity, intravesical instillation-based photodynamic therapy (PDT) for bladder cancer (BCa) would demonstrate significant advantages in comparison with the intravenous route. Actually, the low transmucosal efficiency, hypoxia regulation deficiency, as well as the biosafety risks of intravesical drug agents all have greatly limited the clinical development of instillation-based PDT for BCa. Herein, based on our recent findings on bladder intravesical vectors and photodynamic treatment, we explore and find that the conventional antiparasitic agent nitazoxanide (NTZ) by mixing with chlorine e6 (Ce6) conjugated human serum albumin (HSA), HSA-Ce6, is capable of forming self-assembled HSA-Ce6/NTZ nanoparticles (NPs). Then, the HSA-Ce6/NTZ complexes further fabricate with fluorinated chitosan (FCS), the synthesized transmucosal carrier, to form a biocompatible nanoscale system HSA-Ce6/NTZ/FCS NPs, which exhibit remarkably improved transmucosal delivery and uptake capacities compared with HSA-Ce6/NTZ alone or non-fluorinated HSA-Ce6/NTZ/CS NPs. Meanwhile, due to the metabolic regulation of tumor cells by NTZ, the tumor hypoxia could be efficaciously ameliorated to further favor PDT. This work represents a new photosensitizer nanomedicine formulation for the perfection of PDT performance through the modulation of tumor hypoxia by clinically approved agents. Thus, intravesical instillation of HSA-Ce6/NTZ/FCS NPs with favorable biocompatibility, followed by cystoscope-mediated PDT, could achieve a dramatically improved therapeutic effect to ablate orthotopic bladder tumors.

Mucoadhesion and Mechanical Assessment of Oral Films.

Aligned with efforts to overcome shortcomings of conventional oral dosage forms, mucoadhesive oral thin films have been the focus of drug development. Transmucosal drug delivery through oral cavity is a popular alternative to deliver many drugs due to several advantages over conventional oral delivery including greater bioavailability due to bypassing the first-pass effect and avoiding enzymatic or acid-related degradation in the gastrointestinal tract, faster onset of action, and better patient compliance particularly in geriatric and pediatric patients. Furthermore, among solid transmucosal delivery platforms, buccal and sublingual strips or patches are more attractive due to their flexibility, ease of administration, high patient compliance, and fast dissolution. They are also more stable compared to oral gels making them a desirable candidate to deliver many small and large molecules locally or systemically. Mucoadhesion and mechanical properties of oral films are crucial in their performance, and therefore ways to measure these properties are also similarly important. Since they are relatively new to the pharmaceutical market, there are currently no FDA-recommended or USP standard methods available to characterize such dosage forms. This review intends to cover and discuss various methods cited in the literature to measure and evaluate mucoadhesive and mechanical properties of oral films.

On the Suitability of Porcine Labial Mucosa as a Model for Buccal Mucosal Drug Delivery Research.

Contrary to human, porcine mucosa of the inner side of the lip is parakeratinized. Thus, although desirable due to its large surface area, it does not closely resemble human buccal mucosa to be considered a suitable model for systemic drug delivery research. Nevertheless, it can be utilized for comparative screening of topical or systemic delivery of bioactive agents, mostly lipophilic such as cannabinoids.