Prophylactic antibiotics has no benefit for outcome in clean myringoplasty-A register-based cohort study from SwedEar.

OBJECTIVES: To investigate if prophylactic antibiotics (PA) in conjunction with myringoplasty of clean and uninfected ears entails a reduction of postoperative infections within 6 weeks after surgery, and whether it affects the healing rate of the tympanic membrane (TM) at follow-up, 6-24 months after surgery. DESIGN: A retrospective cohort study of prospectively collected data. SETTING: Data extracted from The Swedish Quality Register for Ear Surgery (SwedEar), the years 2013-2019. PARTICIPANTS: All patients in SwedEar with a registered clean conventional myringoplasty (tympanoplasty type I) including a follow-up visit. MAIN OUTCOME MEASURES: The effect of PA use on TM healing rate at follow-up and postoperative infection within 6 weeks of surgery. RESULTS: In the study group (n = 1665) 86.2% had a healed TM at follow-up. There was no significant difference between the groups that had PA administered (87.2%) or not (86.1%). A total of 8.0% had a postoperative infection within 6 weeks. Postoperative infection occurred in 10.2% of the group that received PA (n = 187) compared with 7.7% of the group that did not receive PA. However, this difference was not statistically significant. Postoperative infection within 6 weeks significantly lowered the frequency of healed TMs. CONCLUSION: PA administered during clean conventional myringoplasty does not improve the chance of having a healed TM at follow up, nor decrease the risk of having a postoperative infection within 6 weeks after surgery.

Direct Delivery of Antisense Oligonucleotides to the Middle and Inner Ear Improves Hearing and Balance in Usher Mice.

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane injection, and topical tympanic membrane application. We demonstrate, for the first time, that ASOs delivered directly to the ear correct Ush1c expression in inner ear tissue, improve cochlear hair cell transduction currents, restore vestibular afferent irregularity, spontaneous firing rate, and sensitivity to head rotation, and successfully recover hearing thresholds and balance behaviors in USH1C mice. We conclude that local delivery of ASOs to the middle and inner ear reach hair cells and can rescue both hearing and balance. These results also demonstrate the therapeutic potential of ASOs to treat hearing and balance deficits associated with Usher syndrome and other ear diseases.

Biocompatibility and Therapeutic Effect of 3 Intra-Tympanic Drug Delivery Vehicles in Acute Acoustic Trauma.

INTRODUCTION: The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. MATERIALS AND METHODS: After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (n = 15), hyaluronic acid (HA) + D (n = 17), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP) + D (n = 24). RESULTS: No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (<1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. DISCUSSION/CONCLUSION: HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.

Comparison of intratympanic dexamethasone therapy and hyperbaric oxygen therapy for the salvage treatment of refractory high-frequency sudden sensorineural hearing loss.

OBJECTIVE: This study aimed to compare the efficacy of intratympanic dexamethasone (ITD) therapy and hyperbaric oxygen(HBO) therapy for the salvage treatment of patients with high-frequency sudden sensorineural hearing loss (SSNHL) after the failure of conventional therapy. MATERIALS AND METHODS: 104 refractory high-frequency SSNHL patients were enrolled in our study. Among them, 31 received ITD alone (ITD group), 32 received HBO alone (HBO group) and 41 received no salvage therapies (control group). Hearing outcomes were determined by pure-tone average measured by audiometry. The total effective rates in the hearing recovery and improvement of tinnitus were calculated before and after salvage treatment. RESULTS: There was no significant difference of the total effective rates in the hearing recovery between ITD and HBO group (p = 0.368). However, ITD therapy showed much better improvements of tinnitus than HBO therapy (p = 0.039). After ITD and HBO therapy, there were no significant differences in hearing gains at 2 and 4 KHz between ITD and HBO group (p = 0.468 and 0.934, respectively). Nevertheless, ITD therapy showed significant improvements of hearing gains at 8 KHz (p = 0.049) compared to that of HBO therapy. CONCLUSION: ITD therapy may have better improvements of tinnitus and hearing gains at 8 KHz than HBO therapy in patients with refractory high-frequency SSNHL.

Effects of intratympanic dexamethasone on noise-induced hearing loss: An experimental study.

AIM: Aim of the study was to evaluate the effect of intratympanic steroid treatment on hearing based on oto-acoustic emission. METHODS: A total of 16 healthy female Wistar albino rats weighing were used in this study. They were divided in to 2 groups and each group was exposed to noise at 110dB for 25min to induce acoustic trauma. Intratympanic dexamethasone was administered to the middle ears of animals in the experimental group on the same day as exposure to noise. The control group was given 0.09% saline solution. Distortion product otoacoustic emission measurements were performed on days 7 and 10. RESULTS: There were no differences between the emission results of two groups before treatment at 4004, 4761, 5652, 6726, and 7996Hz. There were significant group differences on measurement days 7 and 10 at all frequencies. CONCLUSION: Our study revealed a significant difference in DPOAE measurements on days 7 and 10 between the experimental and control groups. We detected a positive effect of dexamethasone on noise-induced hearing loss.

Rate of tympanic membrane perforation after intratympanic steroid injection.

PURPOSE: To determine the rate of persistent tympanic membrane perforation after intratympanic steroid injection. To determine which comorbid conditions and risk factors are associated with prolonged time to perforation closure following intratympanic steroid injection. MATERIALS AND METHODS: Clinical data were gathered for patients who had undergone intratympanic steroid injection to treat sudden sensorineural hearing loss or Ménière's disease. Primary outcomes analysis included rate of persistent tympanic membrane perforation, defined as perforation at least 90days following last injection, and time to perforation healing. Age, sex, number of injections, smoking status, diabetes mellitus, previous head and neck irradiation, and concurrent oral steroids, were analyzed as potential predictors of persistent perforation. RESULTS: One hundred ninety two patients were included in this study. Three patients (1.6%) had persistent tympanic membrane perforations. All three patients received multiple injections. One patient underwent tympanoplasty for repair of persistent perforation. The median time to perforation healing was 18days. There was no statistically significant variable associated with time to perforation healing. However, patients with prior history of head and neck radiation averaged 36.5days for perforation healing compared to 17.5days with no prior history of radiation and this approached statistical significance (p=0.078). CONCLUSIONS: The rate of persistent tympanic membrane perforation following intratympanic steroid injection is low. Patients with a history of radiation to the head and neck may be at increased risk for prolonged time for closure of perforation.

Safety and Efficacy of Chitosan-Dextran Hydrogel in the Middle Ear in an Animal Model.

OBJECTIVES: To investigate the efficacy of chitosan-dextran hydrogel (CDH) in preventing postoperative adhesions between the tympanic membrane (TM) and intratympanic structures, and to evaluate its ototoxicity in an animal study. METHODS: In the first step, ototoxicity was evaluated with 7 male albino guinea pigs (GPs) via auditory brainstem responses (ABR) before and 4 weeks after unilateral intratympanic injection of CDH and saline solution contralaterally. In the second step, 12 GPs underwent bilateral ear surgery. The middle ear (ME) mucosa was abraded, and the cavity was filled with CDH on one side and packed with Gelfoam on the contralateral side. A control group of 6 GPs underwent the same procedure except that no material was applied in the ME. The animals were euthanized at the end of the 7th week, and otomicroscopic findings were noted and the temporal bones harvested for the histologic examination. The findings were scored and compared. RESULTS: There was no statistically significant difference between the pre- and postoperative ABR thresholds. In the otomicroscopic findings, the most prominent difference between the two groups was the presence of retraction of the TM in the Gelfoam group. The histopathologic findings revealed a higher degree of inflammation in the Gelfoam group compared with the CDH group. CONCLUSION: This study demonstrated that CDH has no ototoxic effects in GPs. Its use as an ME packing material revealed significantly less TM retraction and inflammatory reaction compared with Gelfoam.

No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor.

CONTEXT: Heparin-binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane (TM). OBJECTIVE: Our aim was to determine whether the doses of HB-EGF delivered in a sustained release hydrogel into a middle ear mouse model, would be measurable in the systemic circulation. We also aimed to observe, in the scenario that the intended dose was absorbed directly into the circulation, whether these levels could be measured above the background levels of HB-EGF in the circulation. METHODS: A total of 12 mice had transtympanic injections of 5 µg/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10 µg/kg of HB-EGF. Intravenous blood samples were collected at 0-, 3-, 24-, 168-, 288- and 720-h post-injection. A double-antibody sandwich one-step process enzyme-linked immunosorbent assay (ELISA) was used to determine the level of HB-EGF in the serum. RESULTS: No mice in the transtympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls. DISCUSSION: The inability of the positive control to measure levels above background, suggest the total dose used in our studies, even if 100% absorbed into the system circulation is insignificant. CONCLUSIONS: HB-EGF at the doses and delivery method proposed for treatment of chronic TM perforation in a mouse model are likely to have no measurable systemic effect.

Hearing outcome does not depend on the interval of intratympanic steroid administration in idiopathic sudden sensorineural hearing loss.

We studied the effect of intratympanic steroid administration with different intervals on hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The subjects were 197 consecutive patients (197 ears) with ISSNHL (hearing level ≥40 dB, interval between onset and treatment ≤30 days). They received systemic administration of prednisolone (100 mg followed by tapered doses) combined with intratympanic injection of dexamethasone (4 mg/ml). Intratympanic injection was performed once a week for 4 weeks in 105 patients (long-interval group), or 4 times in 1 week in 92 patients (short-interval group). The hearing outcomes were evaluated at two points of time: 1 week from the start of treatment, and 1-2 months after the completion of treatment when the hearing level reached a plateau. There was no significant difference in the cure rate, marked-recovery rate, recovery rate, hearing gain, hearing level, or percent hearing improvement between the long- and short-interval groups at either point of time. Multiple regression analysis also showed that the final hearing level did not depend on the interval of intratympanic steroid injection. These results indicate that the hearing outcome of ISSNHL does not improve even if the interval of intratympanic injection is shortened. This implies that a lower total number of intratympanic steroid injections may be as effective as the present protocol.

The impact of topical and systemic enoxaparin sodium use on traumatic tympanic membrane perforation and myringosclerosis.

The objective of this study is to investigate the effect of topical and systemic enoxaparin sodium on the healing pattern of experimentally induced tympanic membrane perforation and formation of myringosclerosis. A total of 24 Wistar-Albino strain rats were included in the study. Standard myringotomies were performed on each rat. In the first group, isotonic serum physiologic was dropped on external ear canal (control group). Topical enoxaparin was dropped on external ear canal and daily topical doses of enoxaparin were dropped on external ear canal of the rats for 14 days (topical treatment group). Third group received subcutaneous injections of enoxaparin for 14 days (systemic treatment group). Five micrometer thick sections of the bullae of the rats were stained with H&E. Inflammation, edema and sclerotic lesions and neovascularization observed in the lamina propria layer of the tympanic membrane, and total thickness of the tympanic membrane were evaluated. In intergroup comparisons, significant difference in the distribution pattern of severity of inflammation in all three groups was not observed (p = 0.784, p > 0.05). Total TM thickness differed among all three groups (p = 0.028, p < 0.05). A statistically significant difference was observed between the systemic enoxaparin and the control groups (p = 0.022, p < 0.05). A statistically significant difference was observed between the topical enoxaparin and the control groups (p = 0.037, p < 0.05). However, comparison between the topical and systemic treatment groups could not reveal any statistically significant intergroup difference (p = 0.682, p > 0.05). A significant difference was not observed among three groups as for the distribution of myringosclerotic plaques, severity of edema and neovascularization in the lamina propria (p = 0.539, p > 0.05), (p = 0.063, p > 0.05), (p = 0.152, p > 0.05). Topical and systemic enoxaparin treatment did not prevent formation of sclerotic plaques; however, it decreased TM thickness significantly in comparison with the control group.

The effect of ofloxacin otic drops on the regeneration of human traumatic tympanic membrane perforations.

OBJECTIVE: To investigate the effects of direct application of ofloxacin otic drops on human traumatic tympanic membrane perforations (TMPs). STUDY DESIGN: Prospective, sequential allocation, controlled clinical study. SETTING: Tertiary university hospital. PARTICIPANTS: In total, 149 patients with traumatic TMPs were recruited. They were allocated sequentially to two groups: a conservative observation group (n = 75) and a ofloxacin drops-treated group (n = 74). MAIN OUTCOME MEASURES: The closure rate, closure time and rate of otorrhoea were compared between the groups at 6 months. RESULTS: In total, 145 patients were analysed. The closure rates of medium perforations between the groups were not significantly different (P = 0.35); however, the ofloxacin drops-treated group had a significantly shorter closure time for medium perforations than the observation group (P < 0.01). Additionally, the ofloxacin drops-treated group showed improvement in the closure rate of large perforations (P = 0.02) and a significantly shorter mean closure time (P < 0.01) than the observation group. However, purulent otorrhoea was not significantly different between the groups (P = 0.37). CONCLUSIONS: The present findings indicate that the moist eardrum environment resulting from topical application of ofloxacin drops shortened the closure time and improved the closure rate, but did not affect hearing improvement or increase the rate of middle ear infection of large traumatic TMPs. Thus, although traumatic TMPs tend to heal spontaneously, moist therapy can be considered for traumatic, large TMPs in the clinic.

Selecting appropriate dose regimens for AM-101 in the intratympanic treatment of acute inner ear tinnitus.

Inhibition of cochlear N-methyl-D-aspartate (NMDA) receptors with AM-101, a small molecule antagonist delivered by intratympanic injection, represents a novel approach to treat acute tinnitus triggered by glutamate excitotoxicity. An earlier double-blind, randomized, placebo-controlled phase II clinical trial (TACTT0) had demonstrated a significant and dose-dependent improvement in tinnitus triggered by acute acoustic trauma or otitis media from baseline to day 90. A second phase II trial (TACTT1) now sought to evaluate the most appropriate dose regimen for this treatment. Outcomes from the TACTT1 trial showed no significant difference in tinnitus improvement between a single-dose treatment and a dose regimen comprising three doses over 2 weeks. Taken together, three injections over 3 consecutive days showed the best results in the two phase II trials, suggesting that repeated and concentrated inhibition of cochlear NMDA receptors provides best treatment effects, while keeping the procedural impact on patients short.

Intratympanic dexamethasone versus high dosage of betahistine in the treatment of intractable unilateral Meniere disease.

PURPOSE: The objective of our randomized, double-blind study was to compare the effectiveness of intratympanic (IT) dexamethasone versus high-dosage of betahistine in the treatment of patients with intractable unilateral Meniere disease (MD). MATERIALS AND METHODS: Sixty six patients with definite unilateral MD were randomly divided in two groups: Group A received a combination of IT dexamethasone (DX) and identical-appearing placebo pills while Group B received a combination of high-dosage betahistine and IT saline. Intratympanic injections were repeated for three times with an interlude of 3days. High-dosage of betahistine entailed 144mg/day. Mean outcome measures consisted of vertigo control, pure tone average (PTA), speech discrimination score, Functional Level Score, Dizziness Handicap Inventory and Tinnitus Handicap Inventory. RESULTS: Fifty nine patients completed the study and were available at 12months for analysis. In Group A complete vertigo control (class A) was attained in 14 patients (46.6%) and substantial control (class B) in 7 patients (20%). In Group B, 12 patients (41%) achieved complete vertigo control (class A), 5 patients (17%) substantial control (class B). There is no statistical difference in vertigo control between the two treatment groups. In Group A hearing was unchanged in 14 patients and improved in 4 patients, while in Group B hearing was unchanged in 16 patients and improved in 2 patients. CONCLUSIONS: Our preliminary results demonstrate that high-dosage of betahistine achieved similar outcomes as IT dexamethasone in the control of vertigo and hearing preservation.

After myringotomy, can topical Mesna application be an alternative method to ventilation tube application?

Sodium-2-mercaptoethanesulfonate (Mesna) is a mucolytic substance that is also used for chemically assisted tissue dissection in otological surgery. We investigated the effects of Mesna as a chemical agent on the closing time of perforation of the eardrum in an experimental animal model. We performed simple myringotomy with a knife on 44 tympanic membranes of 22 rats. Four rats were excluded from the study because of serosity in their ears. Rats were divided into two study groups and a control group. These groups were the Mesna-administered group (Group A) (8 rats, 15 tympanic membranes), the saline-administered group (Group B) (8 rats, 14 tympanic membranes) and the control (native) group (6 rats, 11 tympanic membranes) (Group C). We applied Mesna locally for 20 min following myringotomy. Examination was made with an otoendoscope on days 1, 2, 3, 5, and 7, and patency rates were recorded. According to our results, we found that the closing time of the tympanic membrane was significantly longer in the Mesna group than in the saline administrated and native group. After myringotomy procedure, the application of a single dose of Mesna may contribute to the recovery duration of middle-ear pathologies by delaying the closing time of tympanic membrane perforation. However, Mesna cannot be an alternative method for the application of ventilation tubes.

Effects of polylactic acid film on middle ear mucosa and cochlear function in Guinea pigs.

Our aim was to assess the effects of polylactic acid (PLA) on middle ear mucosa and cochlea, to be used as a film barrier for postoperative adhesion prevention in the middle ear. Twenty-one albino Guinea pigs were included in the study. A window was opened on both tympanic bulla and on one side PLA material was placed in the middle ear and on the other side only fenestration was performed and used as a control. All Guinea pigs underwent evaluation of tympanic membranes microscopically; functional hearing was analyzed by auditory brainstem responses preoperatively, in the first and the sixth month. All Guinea pigs were killed on the sixth month for histopathologic evaluation of their temporal bones. There was no statistical difference between both groups regarding hearing thresholds, interpeak wave latencies preoperatively and on first and the sixth months postoperatively. Histopathological evaluation revealed no specific changes. There was a mild local inflammation both in the PLA implanted and control ears. PLA film barrier most likely has no toxic effects on Guinea pig middle ear and does not show any ototoxic side effects.

Effects of basic fibroblast growth factor dose on traumatic tympanic membrane perforation.

OBJECTIVE: To compare the healing outcomes of higher and lower doses of basic fibroblast growth factor (bFGF) on human traumatic tympanic membrane perforation (TMP). STUDY DESIGN: Prospective clinical study. METHODS: All patients with traumatic TMP were treated by direct application of bFGF, and were sequentially allocated into one of two groups: lower-dose group (2-3 drops of bFGF solution daily, approximately 0.1-0.15 mL) and higher-dose group (5-6 drops of bFGF solution daily, approximately 0.25-0.3 mL). The results of closure rate, closure time, and rate of otorrhea between the higher- and lower-dose groups were compared at 3 months. RESULTS: In total, 126 patients were included in this study. The higher-dose group showed significantly improved purulent otorrhea rate compared with the lower-dose group (p < 0.01) for perforations of the same size, although the closure rate of the middle-sized perforations did not differ significantly between higher- and lower-dose groups (p > 0.05). However, the lower-dose group had a significantly shorter closure time of 5 d compared with the higher-dose group (p < 0.05). In addition, although the lower-dose group showed shorter healing times (about 3 d) compared to the higher-dose group for large-sized perforations, the dosage of bFGF did not significantly affect the large-sized perforation closure rate (p > 0.05) or closure time (p > 0.05). Nine large-sized perforations with secondary purulent otorrhea achieved complete closure, with closure times of 7-25 (14.2 ± 5.8) d. CONCLUSION: This study suggested that continued daily application of a lower dose of bFGF not only shortens the closure time of human traumatic TMP but also avoids secondary purulent otorrhea.

Sustained release of triamcinolone acetonide from an intratympanically applied hydrogel designed for the delivery of high glucocorticoid doses.

The pharmacokinetic properties and tolerability of a triamcinolone acetonide poloxamer 407 hydrogel for intratympanic application were investigated in a guinea pig model. Evaluation of in vivo release kinetics showed very high initial perilymph drug levels, with clinically relevant levels present for a minimum of 10 days. Assessment of auditory brainstem response thresholds showed a minimal, delayed and transient threshold shift, which was apparent on day 3 and resolved by day 10. No relevant histological changes of the middle and inner ear structures were noted, and hair cell counts showed no significant differences between treated and untreated ears. Thus, the triamcinolone-acetonide-loaded poloxamer 407 hydrogel is an effective vehicle for sustained high-dose inner ear glucocorticoid delivery.

TGF-α/HA complex promotes tympanic membrane keratinocyte migration and proliferation via ErbB1 receptor.

Tympanic membrane perforations are common and represent a management challenge to clinicians. Current treatments for chronic perforations involve a graft surgery and require general anaesthesia, including associated costs and morbidities. Bioactive molecules (e.g. growth factors, cytokines) play an important role in promoting TM wound healing following perforation and the use of growth factors as a topical treatment for tympanic membrane perforations has been suggested as an alternative to surgery. However, the choice of bioactive molecules best suited to promote wound healing has yet to be identified. We investigated the effects of hyaluronic acid, vitronectin, TGF-α, IL-24 and their combinations on migration, proliferation and adhesion of cultured human tympanic membrane-derived keratinocytes (hTM), in addition to their possible mechanisms of action. We found that TGF-α, TGF-α/HA and TGF-α/IL-24 promoted wound healing by significantly increasing both migration and proliferation. TGF-α and/or HA treated cells showed comparable cell-cell adhesion whilst maintaining an epithelial cell phenotype. With the use of receptor binding inhibitors for ErbB1 (AG1478) and CD44 (BRIC235), we revealed that the activation of ErbB1 is required for TGF-α/HA-mediated migration and proliferation. These results suggest factors that may be incorporated into a tissue-engineered membrane or directly as topical treatment for tympanic membrane perforations and hence reduce the need for a surgery.

Effects of oral intake of cetirizine HCl and desloratadine molecules on the middle ear mucosa: an experimental animal study.

We have planned to demonstrate histopathologic effects of mid- or long-term oral use of desloratadine and cetirizine HCl molecules on middle ear mucosa of rats. Thirty-six rats were randomized equally into six groups. Desloratadine groups received once daily doses of 1 mg/ml desloratadine for 30 (D30 Group) or 60 (D60 Group) days. The Cetirizine study groups were given once daily doses of 1 mg/ml cetirizine for 30 (S30 Group) or 60 (S60 Group) days. Control groups were given 2 cc physiologic saline using orogastric gavage method through a 12 G gavage catheter for 30 (K30 Group) or 60 (K60) days. At the end of 30 days, D30, S30 and K30 Groups were sacrificed. Tissue samples harvested from groups were evaluated between 1 and 4 Grades for histological characteristics of middle ear canal, eardrum, middle ear epithelium and connective tissue, edema, vascular congestion and inflammatory cells. In the control group no pathological finding was encountered in rats sacrificed on 30 and 60 days. No statistical difference was observed when groups were compared on external ear epithelial tissue, external ear sebaceous gland, middle ear inflammation, and middle ear capillary dilatation both on 30 and 60 days. Tympanic membrane collagen was more evident in D30 and D60 groups when compared with C30 and C60 groups. Comparison of histopathological grading results between 30 and 60 days revealed no significant changes. In conclusion, oral intake of cetirizine and desloratadine preparations has effects of tympanic membrane collagen, degrees of edema and vascular congestion being more prominent with desloratadine molecule.

A Pseudo-Surfactant Chemical Permeation Enhancer to Treat Otitis Media via Sustained Transtympanic Delivery of Antibiotics.

Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable noninvasive drug delivery across skin-like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, can compromise gelation, formulation stability, and drug diffusion. To overcome this challenge, differing interactions between CPEs and the hydrogel system are explored, especially those with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and those with methyl laurate (ML), a nonionic counterpart with a similar length alkyl chain. Notably, the use of ML effectively decouples permeation enhancement from gelation, enabling sustained delivery across TMs to treat acute otitis media (AOM), which is not possible with the use of SDS. Ciprofloxacin and ML are shown to form a pseudo-surfactant that significantly boosts transtympanic permeation. The middle ear ciprofloxacin concentration is increased by 70-fold in vivo in a chinchilla AOM model, yielding superior efficacy and biocompatibility than the previous highest-performing formulation. Beyond improved efficacy and biocompatibility, this single-CPE formulation significantly accelerates its progression toward clinical deployment.