Self-emulsifying drug delivery systems: a novel approach to deliver drugs

Self-emulsifying drug delivery systems (SEDDS) are a proven method for poorly soluble substances works by increasing the solubility and bioavailability. SEDDS and isotropic mixtures, are composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce microemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water phase along the GI tract might be a promising technique for lipophilic agents with dissolution rate-limited absorption. This review provides an outline of SEDDS''s numerous advances and biopharmaceutical elements, types, manufacturing, characterization, limitations, and future prospects. The evaluation of SEDDS and its applications are also discussed, focusing on the advances of SEDDS''s solid self-emulsifying delivery mechanism and dosage form. By integrating suitable polymer into the formulation, SEDDS may be studied for the creation of a formulation with sustained drug release. This technology''s improvement might lead to a new application in the field of medicine delivery. SEDDS has been demonstrated to be quite efficient in increasing oral bioavailability of lipophilic products. SEDDS is one of the promising methods for controlling the characteristics of medications that are not great choices for oral delivery. It is also worth mentioning that SEDDS may be made in variety of solid dosage forms that are acceptable for both oral and parenteral administration.     

Enhanced tumor homing of pathogen-mimicking liposomes driven by R848 stimulation: A new platform for synergistic oncology therapy

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.     

The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.     

Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus (MRSA)

This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to conf...     

Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality

Ischemic stroke accounts for about 87% of all strokes, causing long-term disability in adults, and is the second leading cause of death worldwide. In search of new therapeutic modalities, the use of neuroprotective agents loaded in nanocarriers to be delivered by noninvasive means (i.e. via intranasal route) became a popular approach. In the current study, melatonin (MEL) was loaded in lipidic nanocapsules (LNCs) prepared using the phase inversion method, and characterized in terms of size, polydispersity, zeta potential, in vitro drug release, viscosity, storage stability, and ex vivo permeation across sheep nasal mucosa. Moreover, MEL-LNCs were tested for efficacy in cerebral ischemia/reperfusion (I/R/) injury model through histopathological assessment, and analysis of oxidative stress markers, pro-inflammatory cytokines, and apoptotic markers. Results showed that LNCs exhibited particle size ranging from 18.26 to 109.8 nm, negative zeta potential, good storage stability, spherical morphology, and a burst release followed by a sustained release pattern. LNCs exhibited 10.35 folds higher permeation of MEL than the drug solution across sheep nasal mucosa. Post-ischemic intranasal administration of MEL-LNCs revealed lowering of oxidative stress manifested by a decrease in malondialdehyde levels, and elevation of glutathione and superoxide dismutase levels, lowering of the inflammatory markers tumor necrosis factor-α, NO, myeloperoxidase, and significant inhibition of Caspase-3 activity as an apoptotic marker. Western blot analysis delineated a recovery of protein expression Nrf-2 and HO-1 with downregulation in the parent inflammatory markers nuclear factor kappa B p65, inducible nitric oxide synthase, Bax, and Cytochrome C expressions, and upregulation of B-cell lymphoma-2 Bcl-2, hence promoting neuronal survival. This was supported by histological evidence, revealing significant restoration of hippocampal neurons. In light of the above, it can be concluded that MEL-LNCs could be a promising delivery system for nose to brain delivery for treatment of cerebral ischemia.     

New frontiers of retinal therapeutic intervention: a critical analysis of novel approaches

A recent wave of pharmacologic and technologic innovations has revolutionized our management of retinal diseases. Many of these advancements have demonstrated efficacy and can increase the quality of life while potentially reducing complications and decreasing the burden of care for patients. Some advances, such as longer-acting anti-vascular endothelial growth factor agents, port delivery systems, gene therapy, and retinal prosthetics have been approved by the US Food and Drug Administration, and are available for clinical use. Countless other therapeutics are in various stages of development, promising a bright future for further improvements in the management of the retinal disease. Herein, we have highlighted several important novel therapies and therapeutic approaches and examine the opportunities and limitations offered by these innovations at the new frontier.

KEY MESSAGES

• Numerous pharmacologic and technologic advancements have been emerging, providing a higher treatment efficacy while decreasing the burden and associated side effects.
• Anti-vascular endothelial growth factor (anti-VEGF) and its longer-acting agents have dramatically improved visual outcomes and have become a mainstay treatment in various retinal diseases.
• Gene therapy and retinal prosthesis implantation in the treatment of congenital retinal dystrophy can accomplish the partial restoration of vision and improved daily function in patients with blindness, an unprecedented success in the field of retina.

     

A pilot investigation of e‐cigarette use and smoking behaviour among patients with chronic airway disease or respiratory symptoms

BackgroundThis pilot study aimed to investigate the current status of e‐cigarettes (ECs) use patterns among patients with chronic airway disease or chronic respiratory symptoms and the effects of ECs use on respiratory and mental health.MethodsA cross‐sectional survey was conducted at the outpatient clinic of eight teaching hospitals in South Korea between November 2019 and December 2019. All adult ECs users (19 years and above) who visited the outpatient clinic as a patient with chronic airway disease or chronic respiratory symptoms were eligible to participate in this study.ResultsA total of 51 subjects responded to the survey. Most of the participants were male (92.2%) and the mean age was 41.8 years. Dominant airway diseases were asthma and chronic obstructive pulmonary disease. Most of the subjects had a history of cigarette smoking, and 19 subjects were dual users of current cigarettes and ECs. Most of the subjects started ECs use due to health‐related reasons. When comparing exclusive ECs users and dual users, St. George''s respiratory questionnaire (SGRQ) scores, the proportion of cases with moderate to severe depressive symptoms, and average Fagerstrom test for nicotine dependence scores for ECs were higher in dual users than exclusive ECs users (mean 4.64 vs. 2.38, p = 0.006), respectively.ConclusionMost of the subjects started ECs use due to health concerns, but dual users have more respiratory symptoms and higher nicotine dependence in this pilot study. One hypothesis that comes from these results is that greater nicotine dependence may influence behaviours, habits, and views about ECs. These preliminary observations need confirmation in a large cohort.     

初产妇足月妊娠胎膜早破胎头高浮对分娩方式的影响及处理方法

目的 探讨初产妇足月妊娠胎膜早破胎头高浮对分娩方式的影响及处理方法.方法 选取2011年1月～2013年1月在我院住院分娩与治疗的214例初产足月妊娠胎膜早破胎头高浮且无其他任何相关性疾病的患者作为研究组,再选取同期214例初产足月妊娠胎膜早破胎头入盆且无其他任何相关性疾病的患者作为对照组,记录两组患者的分娩方式、潜伏期及活跃期,对产后新生儿进行Apgar评分和体质检测,对数据进行分析.结果 两组患者在潜伏期低于8小时、8～16小时之间及活跃期低于4小时的人数比较,差异均有统计学意义（均P＜0.05）;两组患者阴道正常顺产和剖宫助产的人数对比,差异均具有统计学意义（均P＜0.05）;两组胎儿宫内窘迫例数、新生儿Apgar评分＜7分例数以及新生儿平均体重比较,差异均具有统计学意义（均P＜0.05）.结论 胎膜早破后胎头高浮极易引起难产且严重危害围产儿体质,产科医护人员需要重视胎膜早破胎头高浮孕妇的临床观察,加强孕妇的孕期保健,产前严密观察孕妇头盆关系,严格试产.