Betamethasone Sodium Phosphate Research Articles

The World Health Organization Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns (ACTION-III) Trial: study protocol for a multi-country, multi-centre, double-blind, three-arm, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at high probability of late preterm birth in hospitals in low- resource countries

BackgroundPreterm birth complications are the leading cause of newborn and under-5 mortality. Over 85% of all preterm births occur in the late preterm period, i.e. between 34 and < 37 weeks of gestation. Antenatal corticosteroids (ACS) prevent mortality and respiratory morbidity when administered to women at high risk of an early preterm birth, i.e. < 34 weeks’ gestation. However, the benefits and risks of ACS in the late preterm period are less clear; both guidelines and practices vary between settings. Emerging evidence suggests that the benefits of ACS may be achievable at lower doses than presently used. This trial aims to determine the efficacy and safety of two ACS regimens compared to placebo, when given to women with a high probability of late preterm birth, in hospitals in low-resource countries.MethodsWHO ACTION III trial is a parallel-group, three-arm, individually randomized, double-blind, placebo-controlled trial of two ACS regimens: dexamethasone phosphate 4 × 6 mg q12h or betamethasone phosphate 4 × 2 mg q 12 h. The trial is being conducted across seven sites in five countries—Bangladesh, India, Kenya, Nigeria, and Pakistan. Eligible women are those with a gestational age between 34 weeks 0 days and 36 weeks 5 days, who have a high probability of preterm birth between 12 h and 7 days (up to 36 weeks 6 days gestation). The primary outcome is a composite of stillbirth or neonatal death within 72 h of birth or use of newborn respiratory support within 72 h of birth or prior to discharge from hospital, whichever is earlier. Secondary outcomes include safety and health utilization measures for both women and newborns. The sample size is 13,500 women.DiscussionThis trial will evaluate the benefits and possible harms of ACS when used in women likely to have a late preterm birth. It will also evaluate a lower-dose ACS regimen based on literature from pharmacokinetic studies. The results of this trial will provide robust critical evidence on the safe and appropriate use of ACS in the late preterm period internationally.Trial registrationISRCTN11434567. Registered on 7 June 2021.

Glutathione-Responsive and Hydrogen Sulfide Self-Generating Nanocages Based on Self-Weaving Technology To Optimize Cancer Immunotherapy.

As an ideal drug carrier, it should possess high drug loading and encapsulation efficiency and precise drug targeting release. Herein, we utilized a template-guided self-weaving technology of phase-separated silk fibroin (SF) in reverse microemulsion (RME) to fabricate a kind of hyaluronic acid (HA) coated SF nanocage (HA-gNCs) for drug delivery of cancer immunotherapy. Due to the hollow structure, HA-gNCs were capable of simultaneous encapsulation of the anti-inflammatory drug betamethasone phosphate (BetP) and the immune checkpoint blockade (ICB) agent PD-L1 antibody (αPD-L1) efficiently. Another point worth noting was that the thiocarbonate cross-linkers used to strengthen the SF shell of HA-gNCs could be quickly broken by overexpressed glutathione (GSH) to reach responsive drug release inside tumor tissues accompanied by hydrogen sulfide (H2S) production in one step. The synergistic effect of released BetP and generated H2S guaranteed chronological modulation of the immunosuppressive tumor microenvironment (ITME) to amplify the therapeutic effect of αPD-L1 for the growth, metastasis, and recurrence of tumors. This study highlighted the exceptional prospect of HA-gNCs as a self-assistance platform for cancer drug delivery.

Comparison of side effects of different steroids used in intratympanic injections

ObjectivesThis study aimed to compare the side effects of different steroids used in the intratympanic injections (IT). MethodsOne hundred and sixty patients diagnosed with sudden sensorineural hearing loss and undergoing IT were assigned to four groups based on the type or concentration of steroids administered (Group DM5: 5 mg/ml Dexamethasone sodium phosphate; Group DM10: 10 mg/ml Dexamethasone sodium phosphate; Group MP: 40 mg/ml Methylprednisolone sodium succinate; Group BM: 4 mg/ml Betamethasone sodium phosphate). Each group comprised 40 patients, and all participants received IT six times. The study assessed and compared the degrees and duration of pain, dizziness, and tympanic membrane damage following IT. Patients were asked to report the pain they felt using the numeric rating scale (NRS). ResultsNRS scores for pain after IT showed significant differences among the four groups (p < 0.001). The average NRS scores for pain in each group were as follows: Group DM5: 1.53 ± 1.04; Group DM10: 1.45 ± 1.30; Group MP: 4.33 ± 2.22; Group BM: 6.03 ± 1.46. The durations of pain after IT also exhibited significant differences among the four groups (p < 0.001), with the longest duration observed in Group MP at 31.93 ± 15.20 min. ConclusionDifferent types of steroids could lead to varying degrees of pain when used in IT. Betamethasone could cause the most severe pain, and methylprednisolone could result in the longest duration of pain.

Comparison of Intravascular Versus Intramuscular Betamethasone Phosphate on Neonatal Outcomes in the Cases of Imminent Preterm Birth

Comparison of Intravascular Versus Intramuscular Betamethasone Phosphate on Neonatal Outcomes in the Cases of Imminent Preterm Birth

Postnatal budesonide improved lung function in preterm lambs exposed to antenatal steroids and chorioamnionitis.

A combination of budesonide and surfactant decreases the rates of BPD in infants and lung injury in preterm sheep. Whether this combination will show benefit in the setting of chorioamnionitis and antenatal steroids is not known. Ewes at 123 ± 1 day gestational age received intra-amniotic (IA) injections of 10 mg LPS before being randomized to receive either 0.25 mg/kg maternal betamethasone phosphate and acetate or saline by intramuscular (IM) injection at 48 and 24 h prior to delivery at 125 ± 1 day. Lambs (N = 6-9/group) underwent intentionally injurious ventilation for 15 min, then lambs received surfactant mixed with either: (1) saline; or (2) Budesonide 0.25 mg/kg and were ventilated for 4 h. Compared with LPS-exposed animals that received no IM steroid treatment, betamethasone exposed fetuses had improved hemodynamic stability, lung compliance, and ventilation efficiency. The addition of budesonide to surfactant further improved markers of injury and pro-inflammatory cytokine mRNA in both betamethasone IM or no IM lambs exposed to LPS IA. Antenatal betamethasone and IA LPS exposures decreased budesonide levels in the fetal lung and plasma. Antenatal betamethasone stabilizes physiologic parameters in LPS treated lambs. Budesonide mixed with surfactant further decreases injury and improves respiratory physiology in betamethasone treated animals. Antenatal betamethasone improved lung and systemic physiology in the setting of intra-amniotic LPS. The addition of budesonide to the surfactant further improved lung function. Budesonide levels in the plasma and lung were lower in lambs exposed to either LPS or LPS and Betamethasone animals, and these findings were not explained by increased esterification in the lungs. The combination of antenatal steroids and budesonide with surfactant had the lowest markers of pro-inflammatory cytokines in the lung of LPS exposed animals.

Biphasic release of betamethasone from an injectable HA hydrogel implant for alleviating lumbar disc herniation induced sciatica

Epidural steroid injection (ESI) is a common therapeutic approach for managing sciatica caused by lumbar disc herniation (LDH). However, the short duration of therapeutic efficacy and the need for repeated injections pose challenges in LDH treatment. The development of a controlled delivery system capable of prolonging the effectiveness of ESI and reducing the frequency of injections, is highly significant in LDH clinical practice. In this study, we utilized a thiol-ene click chemistry to create a series of injectable hyaluronic acid (HA) based release systems loaded with diphasic betamethasone, including betamethasone dipropionate (BD) and betamethasone 21-phosphate disodium (BP) (BD/BP@HA). BD/BP@HA hydrogel implants demonstrated biocompatibility and biodegradability to matched neuronal tissues, avoiding artificial compression following injection. The sustained release of betamethasone from BD/BP@HA hydrogels effectively inhibited both acute and chronic neuroinflammation by suppressing the nuclear factor kappa-B (NF-κB) pathway. In a mouse model of LDH, the epidural administration of BD/BP@HA efficiently alleviated LDH-induced sciatica for at least 10 days by inhibiting the activation of macrophages and microglia in dorsal root ganglion and spinal dorsal horn, respectively. The newly developed HA hydrogels represent a valuable platform for achieving sustained drug release. Additionally, we provide a simple paradigm for fabricating BD/BP@HA for epidural injection, demonstrating greater and sustained efficiency in alleviating LDH-induced sciatica compared to traditional ESI and displaying potentials for clinical translation. This system has the potential to revolutionize drug delivery for co-delivery of both soluble and insoluble drugs, thereby making a significant impact in the pharmaceutical industry. Statement of SignificanceLumbar disc herniation (LDH) is a common degenerative disorder leading to sciatica and spine surgery. Although epidural steroid injection (ESI) is routinely used to alleviate sciatica, the efficacy is short and repeated injections are required. There remains challenging to prolong the efficacy of ESI. Herein, an injectable hyaluronic acid (HA) hydrogel implant by crosslinking acrylated-modified HA (HA-A) with thiol-modified HA (HA-SH) was designed to achieve a biphasic release of betamethasone. The hydrogel showed biocompatibility and biodegradability to match neuronal tissues. Notably, compared to traditional ESI, the hydrogel better alleviated sciatica in vivo by synergistically inhibiting the neuroinflammation in central and peripheral nervous systems. We anticipate the injectable HA hydrogel implant has the potential for clinical translation in treating LDH-induced sciatica.

A case of anti-laminin γ1 (p200) pemphigoid developed after dipeptidyl peptidase-4 inhibitor administration.

A 73-year-old man with diabetes mellitus was referred to our department for ultraviolet treatment for erythematous skin lesions with itching. On dipeptidyl peptidase-4 inhibitor (DPP-4i) sitagliptin (Januvia®) for diabetes mellitus, the erythematous skin lesions appeared and spread to the whole body. At the initial visit, erythema multiforme-like skin lesions with crusts were observed on the trunk and extremities, and the patient was suspected to have drug eruption. Histopathology demonstrated eosinophilic infiltration in the superficial dermis and inflammatory cell infiltration in the epidermis. Sitagliptin was discontinued, and erythematous lesions improved with oral prednisolone. Thereafter the patient was treated with phototherapy and betamethasone sodium phosphate infusion for residual prurigo. However, blistering skin lesions appeared 5 months later. Histopathological findings were subepidermal blisters with eosinophilic abscess, and bullous pemphigoid was suspected. CLEIAs for autoantibodies to desmoglein 1 (Dsg1), Dsg3 and BP180 were negative. Direct immunofluorescence showed linear depositions of immunoglobulin G (IgG) and C3 at the epidermal basement membrane zone, and indirect immunofluorescence detected IgG anti-epidermal basement membrane zone antibodies, reacting with the dermal side of 1M NaCl-split normal human skin. IgG antibodies reacted with 200 kDa laminin γ1 (p200) by immunoblotting using dermal extracts. These results indicated that this patient was diagnosed with anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration. Although reports of DPP-4i-related bullous pemphigoid have accumulated, cases of anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration are rarely reported.

A Pharmacovigilance Study of Drug-Induced Glaucoma Utilizing the Japanese Adverse Event Reporting System.

Clinically, glaucoma is a serious problem because it is asymptomatic until a relatively late stage in most cases, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of glaucoma with the causative drugs using a spontaneous reporting system database. Data were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on reports of glaucoma caused by all drugs, we calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for glaucoma. Among 609 reports of adverse events corresponding to glaucoma (46%, women), the most frequently implicated drug were steroids (prednisolone, betamethasone sodium phosphate, triamcinolone acetonide, and fluorometholone), pregabalin, ranibizumab, crizotinib, tacrolimus hydrate, darbepoetin alfa, and foscarnet sodium hydrate. Among 207 reports involved in angle-closure glaucoma (86%, women), anticholinergic drug and antidepressants ranked high and showed signals. Signals were also detected in bromazepam (ROR, 69.7; 95% CI, 30.9-157.5), oral brotizolam (ROR, 16.6; 95% CI, 6.18-44.8), and oral milnacipran hydrochloride (ROR, 22.8; 95% CI, 8.46-61.4) for angle-closure glaucoma. A national pharmacovigilance database enabled us to identify the drugs that frequently induce glaucoma. The likelihood of the reporting of glaucoma varied among the drugs, which should be used carefully in clinical practice to avoid it.

Analysis of Corticosteroid-Induced Glaucoma Using the Japanese Adverse Drug Event Reporting Database.

Glaucoma is the most common cause of blindness, which significantly reduces quality of life. Most glaucoma cases are primary glaucoma; nevertheless, many patients suffer from glaucoma caused by drugs, such as corticosteroids. A comprehensive review of the risks associated with corticosteroid-induced glaucoma is limited. Therefore, we used the Japanese Adverse Drug Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency (PMDA) to analyze the risk factors associated with glaucoma and the trends and characteristics of corticosteroid-induced glaucoma. We did not find sex or age differences associated with the onset of glaucoma. Hierarchical clustering and principal component analysis revealed that triamcinolone acetonide and betamethasone sodium phosphate, which are used around the eyes in Japan, are more likely to induce intraocular pressure (IOP) elevation compared with other corticosteroids. Increased IOP is a direct cause of glaucoma. Based on these findings, it may be necessary to limit or avoid the use of these corticosteroids.

Remote-controllable dosage management through a wearable iontophoretic patch utilizing a cell phone.

With regard to medical treatment through operations, remote control is possible, however, the area of remote-controllable drug treatment is yet to be established. In this study, a prototyped remote-controllable dosage management system that allows patients and caregivers to administer therapeutic drugs via an internet line without touching the dosage device or formulation was developed. This system consists of a transmitter (System A) located away from the patient, and a dosage device (System B) equipped with a receiver (B1), dosage management unit (B2), and a drug treatment unit (B3) that can be installed on the patient. Additionally, Bluetooth® is adopted to communicate from System A to System B. In the present study, System A was incorporated into a cell phone, and System B was a constant-current iontophoresis (IP) device, which was applied on excised pig skin. Sodium salt of betamethasone phosphate (BP-Na+) was selected as a model drug, and the in vitro skin permeation of BP- was evaluated. As a result, by transmitting the administration information incorporated in System A through B1 to B2, the optimal current was passed between the IP electrodes in B3, and the skin permeation of BP- was obtained by remote control. That is, the skin permeation of BP- was obtained by the current flowing from the IP device. The permeation amount decreased when the voltage load was stopped. These results suggested that remote control from System A enables dosing management of bioactive substances from dosage devices applied on the skin, intracutaneously, or subcutaneously without being near the patient. Although various trials are still required to complete the remote-controlled system, the patient does not have to go to the hospital except to take injections. Such drug administrations would lead to decreased medical expenses and increased quality of life for patients.

Effects of compound betamethasone on vocal fold wound healing in rabbit model: A preliminary study.

The compound betamethasone is widely used to prevent scarring in dermatology. This study aims to explore the effects of compound betamethasone on vocal fold (VF) wound healing. Prospective animal study in rabbits. Eighteen rabbits underwent bilateral VF stripping and three rabbits served as controls. 0.1 mL of compound betamethasone (1mL: betamethasone sodium phosphate 5mg and betamethasone dipropionate 2mg) was injected into the right VF of each rabbit, and 0.1mL 0.9% saline was injected into the contralateral VF. Endoscopy was performed for morphologic observation. Six larynges were harvested for histological analysis at 3 days, 7 days, and 1month. The VFs were stained with hematoxylin and eosin (H&E), Alcian blue, and Masson' trichrome staining. In morphological analysis, there was no visible difference between betamethasone-treated and saline-treated VFs at 3 and 7 days. After 1month, more VF scars appeared on the saline-treated VFs than the VFs treated with betamethasone. Inflammatory cell number showed significant difference between both VFs at 3 days (p=.037) and 7 days (p=.045). No significant different was found in epithelial thickness at 1month between the betamethasone and saline groups. The collagen in the saline-treated VFs was significantly denser than that of the betamethasone-treated group (p=.037). There was also a significant increase in the level of hyaluronic acid(HA) in betamethasone-injected VFs in comparison to the saline-injected VFs (p=.006). Based on this study, compound betamethasone can improve VF healing. Our findings suggest that VF injection with compound betamethasone helps to minimize scarring by increasing HA level and decreasing collagen density.

Development of a Novel Process for the Preparation of the Anti-Inflammatory Drug Betamethasone Sodium Phosphate

In this paper, we report our efforts for the development of a novel and improved preparation of the anti-inflammatory steroidal active pharmaceutical ingredient, namely, betamethasone sodium phosphate. Starting from commercially available betamethasone, the synthetic strategy involved the mesylation of the hydroxyl group at C21 position, followed by the key phosphorylation reaction of the mesylate derivative with potassium di-tert-butyl phosphate, the hydrolysis of the di-tert-butyl ester intermediate under mild acidic conditions, and the final salification. The developed process allowed us to obtain the desired betamethasone sodium phosphate in 68% overall yield at multi-kg scale ≥ 99.9% HPLC purity. Cost-effectiveness of the process, impurity profiling, and material quality are also discussed.

Betamethasone-loaded dissolvable microneedle patch for oral ulcer treatment

Oral inflammatory disease (OID) is among the most common oral lesions, affecting people’s quality of life and even leading to oral cancer. Oral ulcers are the most common OID. However, the pain and fear caused by the localized injection of hormones hinder the clinical treatment of oral ulcers. To address this problem, soluble hyaluronic acid (HA) microneedle patches (BSP-BDP@HAMN) containing betamethasone 21-phosphate sodium (BSP) and betamethasone 17,21-dipropionate (BDP) were fabricated for potential application in oral ulcers. BSP-BDP@HAMNs had the sufficient mechanical strength to penetrate the rat tongue abdomen mucosa with an insertion depth of approximately 207 ± 3 µm. The rapidly solubilized HA microneedle carrier released BSP and BDP into the ulcer base within 3 min of entering the mucosa. Cellular assays have shown that BDP@HAMNs have wound healing-promoting and anti-inflammatory effects. Compared with topical injections and creams, BSP-BDP@HAMNs not only penetrated the ulcer surface painlessly but also worked deep in the ulcer for a long time. In conclusion, the proposed BSP-BDP@HAMN patch can improve the comfort and efficacy of oral ulcer treatment, thus providing a new prospect for oral ulcer treatment.

Injectable Anti-Inflammatory Supramolecular Nanofiber Hydrogel to Promote Anti-VEGF Therapy in Age-Related Macular Degeneration Treatment.

Age-related macular degeneration (AMD) is a major cause of visual impairment and severe vision loss worldwide, while the currently available treatments are often unsatisfactory. Previous studies have demonstrated both inflammation and oxidative-stress-induced damage to the retinal pigment epithelium are involved in the pathogenesis of aberrant development of blood vessels in wet AMD (wet-AMD). Although antivascular endothelial growth factor (VEGF) therapy (e.g., Ranibizumab) can impair the growth of new blood vessels, side effects are still found with repeated monthly intravitreal injections. Here, an injectable antibody-loaded supramolecular nanofiber hydrogel is fabricated by simply mixing betamethasone phosphate (BetP), a clinic anti-inflammatory drug, anti-VEGF, the gold-standard anti-VEGF drug for AMD treatment, with CaCl2 . Upon intravitreal injection, such BetP-based hydrogel (BetP-Gel),while enabling long-term sustained release of anti-VEGF to inhibit vascular proliferation in the retina and attenuate choroidal neovascularization, can also scavenge reactive oxygen species to reduce local inflammation. Remarkably, such BetP-Gel can dramatically prolong the effective treatment time of conventional anti-VEGF therapy. Notably, anti-VEGF-loaded supramolecular hydrogel based on all clinically approved agents may be readily translated into clinical use for AMD treatment, with the potential to replace the current anti-VEGF therapy.

FOXO1 Is a Key Mediator of Glucocorticoid-Induced Expression of Tristetraprolin in MDA-MB-231 Breast Cancer Cells.

The mRNA destabilizing factor tristetraprolin (TTP) functions as a tumor suppressor by down-regulating cancer-associated genes. TTP expression is significantly reduced in various cancers, which contributes to cancer processes. Enforced expression of TTP impairs tumorigenesis and abolishes maintenance of the malignant state, emphasizing the need to identify a TTP inducer in cancer cells. To search for novel candidate agents for inducing TTP in cancer cells, we screened a library containing 1019 natural compounds using MCF-7 breast cancer cells transfected with a reporter vector containing the TTP promoter upstream of the luciferase gene. We identified one molecule, of which the enantiomers are betamethasone 21-phosphate (BTM-21-P) and dexamethasone 21-phosphate (BTM-21-P), as a potent inducer of TTP in cancer cells. We confirmed that BTM-21-P, DXM-21-P, and dexamethasone (DXM) induced the expression of TTP in MDA-MB-231 cells in a glucocorticoid receptor (GR)-dependent manner. To identify potential pathways linking BTM-21-P and DXM-21-P to TTP induction, we performed an RNA sequencing-based transcriptome analysis of MDA-MB-231 cells at 3 h after treatment with these compounds. A heat map analysis of FPKM expression showed a similar expression pattern between cells treated with the two compounds. The KEGG pathway analysis results revealed that the upregulated DEGs were strongly associated with several pathways, including the Hippo signaling pathway, PI3K-Akt signaling pathway, FOXO signaling pathway, NF-κB signaling pathway, and p53 signaling pathway. Inhibition of the FOXO pathway using a FOXO1 inhibitor blocked the effects of BTM-21-P and DXM-21-P on the induction of TTP in MDA-MB-231 cells. We found that DXM enhanced the binding of FOXO1 to the TTP promoter in a GR-dependent manner. In conclusion, we identified a natural compound of which the enantiomers are DXM-21-P and BTM-21-P as a potent inducer of TTP in breast cancer cells. We also present new insights into the role of FOXO1 in the DXM-21-P- and BTM-21-P-induced expression of TTP in cancer cells.

Intraoperative subconjunctival steroid reduces the incidence of pseudophakic macular oedema: a cohort study of 20,066 consecutive phacoemulsification surgeries.

Pseudophakic macular oedema remains the most common sight-threatening complication following cataract surgery. This study aims to assess the effect of intraoperative subconjunctival steroids on the rate of pseudophakic cystoid macular oedema. A retrospective, observational database study of 20 066 consecutive phacoemulsification surgeries. The incidence of pseudophakic cystoid macular oedema was compared in eyes that did and did not receive intraoperative subconjunctival steroid injection during routine cataract surgery. Intraoperative subconjunctival injection of dexamethasone or betamethasone sodium phosphate significantly reduced the odds of developing pseudophakic cystoid macular oedema across the cohort (odds ratio: 0.67; 95% confidence interval: 0.46-0.98, p = 0.039). The effect of subconjunctival steroids on pseudophakic macular oedema remained independently associated on multivariate logistic regression analysis (p = 0.028). This study demonstrates that administration of intraoperative subconjunctival steroid injection is associated with a reduced incidence of pseudophakic cystoid macular oedema in routine, uncomplicated cataract surgery.

Different corticosteroids and regimens for accelerating fetal lung maturation for babies at risk of preterm birth.

Different corticosteroids and regimens for accelerating fetal lung maturation for babies at risk of preterm birth.

Composite dissolvable microneedle patch for therapy of oral mucosal diseases.

A composite microneedle patch (MN patch) is developed for oral transmucosal administration. To improve the oral transmucosal drug delivery efficiency, the composite MN patch is designed to consist of an array of 100 dissolvable microneedles (MNs) with drug-loaded tips and a backing layer. The MNs are composed of two parts, the hyaluronic acid (HA) tip part and the polyvinylpyrrolidone (PVP) base part. Due to the small size and sufficient mechanical strength, the HA-PVP MNs can painlessly penetrate the oral mucosa barrier and deliver drugs directly to the basal layer or submucosa. Betamethasone sodium phosphate (BSP), as the model drug, is concentrated in the HA tip parts to avoid the drug waste caused by mucosa elasticity. Considering the special moist environment and saliva flow in the mouth, a double-layer backing layer composed of a poly(vinyl alcohol) (PVA) adhesive layer and an ethyl cellulose (EC) waterproof layer is designed and constructed, which could reduce the saliva flow effects. The in vitro and in vivo results demonstrate that the MN patch could achieve rapid and efficient BSP release in oral mucosa due to the rapid dissolution of HA. The proposed MN patch provides a novel strategy for the therapy of oral mucosal diseases.

Low-dose antenatal betamethasone treatment achieves preterm lung maturation equivalent to that of the World Health Organization dexamethasone regimen but with reduced endocrine disruption in a sheep model of pregnancy

The intramuscular administration of antenatal steroids to women at risk of preterm delivery achieves high maternal and fetal plasma steroid concentrations, which are associated with adverse effects and may reduce treatment efficacy. We have demonstrated that antenatal steroid efficacy is independent of peak maternofetal steroid levels once exposure is maintained above a low threshold. This study aimed to test, using a sheep model of pregnancy, whether the low-dose antenatal steroid regimen proposed as part of the Antenatal Corticosteroids for Improving Outcomes in Preterm Newborns trial would achieve preterm lung maturation equivalent to that of the existing World Health Organization dexamethasone treatment regimen, but with reduced risk of adverse outcomes. Following ethical review and approval, date-mated ewes with single fetuses received intramuscular injections of either (1) four 6-mg maternal intramuscular injections of dexamethasone phosphate every 12 hours (n=22), (2) 4 2-mg maternal intramuscular injections of betamethasone phosphate every 12 hours (n=21), or (3) 4 2-mL maternal intramuscular injections of saline every 12 hours (n=16). Of note, 48 hours after first injection, (124±1 day), lambs were delivered, ventilated for 30 minutes, and euthanized for sampling. Arterial blood gas, respiratory, hematological, and biochemical data were analyzed for between-group differences with analysis of variance according to distribution and variance, with P<.05 taken as significant. After 30 minutes of ventilation, lambs from both steroid-treated groups had significant and equivalent improvements in lung function relative to saline control (P<.05). There was no significant difference in arterial blood pH, pO2, pCO2, lung compliance, ventilator efficiency index, or lung volume at necropsy with a static pressure of 40 cmH2O. The messenger RNA expression of surfactant protein (Sp)a, Spb, Spc, Spd, aquaporin (Aqp)1, Aqp5, and sodium channel epithelial 1 subunit beta (Scnn1b) was equivalent between both steroid groups. Maternal and fetal plasma neutrophil, glucose, and fetal plasma C-peptide levels were significantly elevated in the dexamethasone group, relative to the betamethasone group. Fetal plasma insulin-like growth factor 1 was significantly reduced in the dexamethasone group compared with the betamethasone group (P<0.05). Fetal adrenocorticotropic hormone (r=0.53), maternal glucose value (r=-0.52), and fetal glucose values (r=-0.42) were correlated with maternal weight in the betamethasone group (P<.05), whereas fetal pCO2 and pO2 were not correlated. There was no significant difference between male and female lamb outcomes in any groups for any of the items evaluated. This study reported that in preterm lambs, a low-dose treatment regimen of 8 mg betamethasone achieves lung maturation equivalent to that of a 24-mg dexamethasone-based regimen, but with smaller perturbations to the maternofetal hypothalamic-pituitary-adrenal axis. These data suggested that given steroid pharmacokinetic differences between sheep and humans, a betamethasone dose of 2 mg may remain above the minimum dose necessary for robust maturation of the preterm lung. Maternal weight-adjusted betamethasone doses might also be a key to reducing perturbations to the maternofetal hypothalamic-pituitary-adrenal axis.

A fast, validated UPLC method coupled with PDA-QDa detectors for impurity profiling in betamethasone acetate and betamethasone phosphate injectable suspension and isolation, identification, characterization of two thermal impurities

For impurity profiling of betamethasone acetate and betamethasone phosphate injectable suspensions, a quick, verified stability indicating UPLC technique incorporating the detectors PDA-QDa had been established. This method with an analysis time of 12min could able to separate all possible degradation impurities. Two of the thermal impurities have been identified in positive mode of detection by using QDa detector and isolated by using preparative HPLC. The method works at a flow rate of 0.5mL/min in column: Poroshell 120 EC C18 (100×2.1)mm, 1.9μm, maintained temperature precisely at 40°C. The M/Z values in ESI positive mode for the two new degradation impurities have been identified (M+H) as 393.22 (DP1), 363.17 (DP2) and confirmed by 1H NMR. The approach was also verified in accordance with the rules of ICH Q2 (R1). From LOQ quantity value to 150% quantity of specified concentration (2% for betamethasone and 0.5% for other impurities), the technique of UPLC-PDA-QDa was proven to be linear and accurate. Precision and ruggedness results showed˂5% RSD. Accuracy results showed more than 95% recovery from LOQ till 150% of impurity specification. This UPLC-PDA-QDa methodology was found specific, precise, stable and robust for quantification of all possible degradation impurities. The proposed method has been transferred to quality control laboratories to access the impurity profile during product storage.