Development of Sedative Dexmedetomidine Sublingual In Situ Gels: In Vitro and In Vivo Evaluations.

Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX sublingual in situ gels were developed and assessed for their pH, gelling capacity, viscosity, mucoadhesion and in vitro drug release. The optimized gelling system demonstrated enhanced mucoadhesion, superior gelling capacity, reasonable pH and optimal rheological profile. In vivo, compared to the oral solution, the optimal sublingual gel resulted in a significant higher rate and extent of bioavailability. Although the in situ gel had comparable plasma levels to those observed following intravenous administration, significant amelioration of the systemic adverse reactions were attained. As demonstrated by the hot plate method, a sustained duration of analgesia in rats was observed after sublingual administration of DEX gel compared to the intravenously administered DEX solution. Furthermore, no changes in systolic blood pressure and heart rate were recorded in rats and rabbits, respectively, after sublingual administration of DEX. Sublingual administration of DEX in situ gel provides a promising approach for analgesia and sedation, while circumventing the reported adverse reactions associated with intravenous administration of DEX.

Stability Study and Clinical Evaluation of Lipid Injectable Emulsion in Parenteral Nutrition Admixtures Used for Preterm Neonates.

BACKGROUND: Intravenous administration of parenteral nutrition (PN) admixtures containing 4-oil lipid injectable emulsion (ILE) in preterm neonates is usually prohibited because of limited clinical data. The authors evaluated the stability, safety, and efficacy of PN admixtures containing 4-oil ILE, for the first time, in preterm neonates. METHODS: A series of PN admixtures were prepared for consecutive administration in preterm neonates over a period of 15 days. Admixture stability was assessed after 24 hours of storage at 25 and 37 °C via visual inspection and measurement of mean droplet size (MDS). Safety and efficacy of the admixtures in preterm neonates were assessed via serum triglyceride levels and body weight increase measurements, respectively. RESULTS: PN admixtures were stable at 25 °C and had MDS ˂500 nm. After 15 days, there was a significant increase in body weight (P ≤ .0001) and level of serum triglycerides (P ≤ .0001), compared with the level before PN administration. CONCLUSIONS: PN admixtures containing 4-oil ILE were stable at 25 °C and showed instability at 37 °C. Therefore, it is recommended to keep the temperature during administration of PN admixtures at 25 °C. PN admixtures were well tolerated and safe over a period of 8 days while providing a balanced fatty acid supply. Tight monitoring of serum triglyceride level is essential, particularly in neonates of low birth weight and/or young gestational age, to avoid hypertriglyceridemia. Hence, the use of these PN admixtures is expected to be beneficial in terms of being cost-effective and reducing the contamination risks.

Severe cutaneous adverse drug reactions: Incidence, clinical patterns, causative drugs and modalities of treatment in Assiut University Hospital, Upper Egypt.

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and overlap SJS/TEN are life-threatening diseases that are most frequently caused by drugs. Much debate remains about the role of systemic corticosteroids (SCs) in their treatment. Our aim to determine the incidence, causative drugs, the role and side effects of SCs in severe cutaneous adverse reactions (SCARs), in Assiut University Hospital (AUH). Patients This study was conducted in Department of Dermatology at AUH, from 2012 to 2017. All patients with SJS, overlap SJS/TEN and TEN admitted during this period were included in the study. Eighty-three patients with SCARs were included in this study. The most common type was SJS (67.5%). The incidence ranged from 1.7% in 2012 to 7.7% in 2017. Carbamazepine, valproic acid, lamotrigine, diclofenac sodium, and flucloxacillin-amoxicillin were the most common causative drugs. The most common side effects of SCs were peptic ulcer (55.5%) and hypertension (51.8%). The mortality rate in patients treated with SCs was 100% in TEN, 33.3% in overlap SJS/TEN and 16.3% in SJS. The patients of SCARs must be aware of the causative drugs and must never be re-administered. SCs in treatment of SCARs may increase the complications and the mortality rate.

Analgesic Effect of Morphine Added to Bupivacaine in Serratus Anterior Plane Block Following Modified Radical Mastectomy. Only a Local Effect? Randomized Clinical Trial.

BACKGROUND: Serratus anterior plane (SAP) block, a novel regional anesthetic procedure, involves the anterolateral chest wall. Opioid receptors have been found on peripheral nerve terminals, so morphine may have a local action. OBJECTIVE: This work aimed at exploring the analgesic efficacy of morphine added to bupivacaine in SAPB in patients for whom modified radical mastectomy was conducted and whether it is a mere local effect. METHODS: Forty female patients were planned to have modified radical mastectomy participated in the study. Patients were randomly divided into two groups; Control group (C): received ultrasound-guided serratus anterior plane block with 20 mL of bupivacaine hydrochloride 0.25%; Morphine group (M): received the same in addition to 10 mg morphine sulfate. Intra- and post-operative blood samples were taken for the assessment of morphine serum levels. All patients were assessed for VAS scores during rest and movement (VAS-R and VAS-M). Time to the first request and the total amount of the rescue analgesia were recorded. RESULTS: In group M, Morphine was not detected in the plasma of all patients. Both VAS-R and VAS-M were significantly higher in group C than in group M (P<0.001) and (P≤0.003), respectively. Time to the first request of rescue analgesia was 8.5 h in group C compared to 20 h in group M (P=0.005) with a median dose of acetaminophen consumption of 2 g in group C compared to 1 g in group M (P=0.006). CONCLUSION: Ten mg of morphine, when added to bupivacaine in SAPB, improved postoperative analgesia in patients to whom modified radical mastectomy was conducted. This effect seems to be attributed merely to local mechanisms. REGISTRATION: The registration number of this study is NCT02962024 at www.clinicaltrial.gov.

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations.

Based on the recent reports of World Health Organization, increased antibiotic resistance prevalence among bacteria represents the greatest challenge to human health. In addition, the poor solubility, stability, and side effects that lead to inefficiency of the current antibacterial therapy prompted the researchers to explore new innovative strategies to overcome such resilient microbes. Hence, novel antibiotic delivery systems are in high demand. Nanotechnology has attracted considerable interest due to their favored physicochemical properties, drug targeting efficiency, enhanced uptake, and biodistribution. The present review focuses on the recent applications of organic (liposomes, lipid-based nanoparticles, polymeric micelles, and polymeric nanoparticles), and inorganic (silver, silica, magnetic, zinc oxide (ZnO), cobalt, selenium, and cadmium) nanosystems in the domain of antibacterial delivery. We provide a concise description of the characteristics of each system that render it suitable as an antibacterial delivery agent. We also highlight the recent promising innovations used to overcome antibacterial resistance, including the use of lipid polymer nanoparticles, nonlamellar liquid crystalline nanoparticles, anti-microbial oligonucleotides, smart responsive materials, cationic peptides, and natural compounds. We further discuss the applications of antimicrobial photodynamic therapy, combination drug therapy, nano antibiotic strategy, and phage therapy, and their impact on evading antibacterial resistance. Finally, we report on the formulations that made their way towards clinical application.