Background:Numerous studies have established that probiotics or prebiotics can relieve the symptoms of allergic rhinitis (AR), but their mechanism of action remain underexplored. This study aimed to observe the clinical efficacy of probiotics combined with prebiotics in seasonal AR patients and explore their underlying mechanisms. Methods:We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. The test group was given probiotics combined with prebiotics, whereas the placebo group was administered simulated preparation for 90 days. Outcome measures included total nasal symptom score (TNSS), visual analog scale, rhinitis quality of life questionnaire, fractional exhaled nitric oxide, and the rate and intensity of Loratadine use. Serum TNF-α, INF-γ, IL-4, IL-17, and IgE levels were measured by enzyme-linked immunosorbent assay. Intestinal microbiota was detected by 16S rRNA gene sequencing and quantitative PCR. Short-chain fatty acids were analyzed by gas chromatography-mass spectrometry. Results:106 participants (N = 53 for both test group and placebo group) completed the study. From baseline to day 91, mean difference between groups (MDBG) in the reduction of TNSS was -1.1 (-2.2, -0.1) (P = 0.04); MDBG in the increment of TNF-α was 7.1 pg/ml (95% CI: 0.8, 13.4, P = 0.03); the INF-γ level was significantly increased (P = 0.01), whereas that of IL-17 (P = 0.005) was significantly decreased in the test group, whilst mean difference within groups was not statistically significant in the placebo group; MDBG in the increment of acetate was 12.4% (95% CI: 7.1%, 17.6%, P <0.001). After the administration of probiotics and prebiotics, the composition and metabolic function of the intestinal microbiota were significantly altered and positively related to the beneficial effect on seasonal AR patients. Conclusion:Probiotics combined with prebiotics administered for 90 days significantly attenuated the symptoms of seasonal AR patients, which may related to fluctuations in the composition and metabolic function of the intestinal microbiota and further ameliorating host immunity.

The safety and efficacy of intratympanic (IT) histamine (HIS) injection as an adjuvant to increase the inner ear penetration of dexamethasone (DEX) was investigated in this study. IT injections of DEX-only, 1% HIS+DEX and 4% HIS+DEX were performed in mice with noise-induced hearing loss. An inflammatory reaction in the middle ear was observed only in the 4% HIS+DEX group although no serious cytotoxic effects on the organ of Corti (OC) were observed at that concentration. Compared with the DEX-only group, the perilymphatic concentration of DEX was approximately two times higher in the 1% HIS+DEX group and approximately five times higher in the 4% HIS+DEX group. The expression of the DEX receptor in the cochlea was significantly increased in the 4%-HIS+DEX group. HIS appeared to induce transient damage the microstructure of the RWM with recovery observed within 3 weeks. The 1 and 4% HIS + DEX groups showed a significant recovery of the OC compared with the control group and they also achieved significantly better hearing restoration at 8 kHz in the DPOAE hearing test (P < .05) when compared to the DEX-only group. IT HIS temporarily disrupts the structure of the RWM and middle ear mucosa and significantly enhances the inner ear penetration of DEX. Therefore, IT HIS injection could be a simple and effective adjuvant therapy to increase perilymph concentration of DEX and achieve OC recovery after cochlear damage.

Steroids (anti-inflammatory drugs) combined with antioxidants are frequently prescribed to treat cisplatin (CP)-induced hearing loss in the clinic. Compared to systemic administration of free drugs, local drug delivery systems offer better therapeutic qualities and patient compliance since they not only can bypass the blood-labyrinth barrier but also can perform sustained release. In this work, dexamethasone (DEX) and lipoic acid (LA) non-spherical microcrystals (MCs) were prepared without complicated chemical modification. Following a series of physical characterizations, including morphology, stability and injectability, dissolution and round window membrane distribution of MCs, DEX MCs, LA MCs and the simple mixture of DEX MCs + LA MCs (combination group) were administered in guinea pigs by intratympanic injection. We found that LA MCs enabled improvement of DEX absorption in the combination group compared to a single dose. In addition, no significant morphological changes or inflammatory responses were observed in cochlear tissue, indicating good biocompatibility. Finally, the combination group also demonstrated synergistic therapeutic effect for protecting hair cells against CP-induced damage. The local co delivery of DEX MCs and LA MCs offers a new strategy for the treatment of CP-induced inner ear injury since they provide sustained anti-inflammatory and antioxidant effects simultaneously.

Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness. The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity. Among them, thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection. This smart biomaterial could transform to semisolid phase when the temperature increased. Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe, efficient, and sustained inner ear drug administration. This article introduces the key techniques and the latest progress in this field.

Neurotology disorders such as vertigo, tinnitus, and hearing loss affect a significant proportion of the population (estimated 39 million in the United States with moderate to severe symptoms). Yet no pharmacological treatments have been developed, in part due to limitations in effective drug delivery to the anatomically protected inner ear compartment. Intratympanic delivery, a minimally invasive injection performed in the office setting, offers a potential direct route of administration. Currently, off-label use of therapeutics approved to treat disorders via systemic administration are being injected intratympanically, mostly in the form of aqueous solutions, but provide variable levels of drug exposure for a limited time requiring repeated injections. Hence, current drug delivery approaches for neurotology disorders are sub-optimal. This review, following a description of pharmacokinetic considerations of the inner ear, explores the merits of novel delivery approaches toward the treatment of neurotology disorders. Methodologies employing local delivery to the inner ear are described, including direct intracochlear delivery as well as intratympanic methods of infusion and injection. Intratympanic injection delivery formulation strategies including hydrogels, polymers and nanoparticulate systems are explored. These approaches represent progress toward more effective delivery options for the clinical treatment of a variety of neurotology disorders.