UNASSIGNED: Dasatinib (DS), a second-generation tyrosine kinase inhibitor, functions as a multi-target small-molecule drug via targeting various tyrosine kinases involved in neoplastic cell growth. DS inhibits cancer cell replication and migration, and induces tumor cell apoptosis in a variety of solid tumors. However, it is poorly soluble in water under some pH values. Therefore, the development of a DS-containing, self-emulsifying, drug delivery system (SeDDs) could help overcome these problems in treating cancer cells.
UNASSIGNED: Various SeDD formulations loaded with DS were developed with isopropyl myristate (oil phase), Labrafil (surfactant), and polyethylene glycol (co-surfactant). The physicochemical properties of the formulations were assessed according to droplet size, encapsulation efficiency, and in vitro drug release. The cytotoxicity of the formulations on the cancer cell lines HT29 and SW420 (human colorectal carcinoma), and MCF7 (human breast adenocarcinoma), in addition to MRC5 normal human fetal lung fibroblasts, was evaluated to assess selectivity.
UNASSIGNED: The DS-SeDD formulation showed favorable particle size, encapsulation efficiency, and in vitro drug release. The anti-cancer potency of DS-SeDDs had greater cytotoxicity effects than pure DA on the three cancer cell lines, MCF7, HT29, and SW420l.
UNASSIGNED: The developed DS-SeDD formulations may potentially be an effective sustained drug delivery method for cancer therapy.
UNASSIGNED: داساتينيب هو مثبط تيروزين كيناز من الجيل الثاني. إنه يعمل كدواء جزيء صغير متعدد الأهداف من خلال استهداف كينازات التيروزين المختلفة التي تشارك في نمو الخلايا الورمية. وقد وجدت التحقيقات الأخيرة أنه يمنع تكاثر الخلايا السرطانية، والهجرة، ويحفز موت الخلايا المبرمج في مجموعة متنوعة من الأورام الصلبة. ومع ذلك، فهو ضعيف الذوبان في الماء تحت ظروف الرقم الهيدروجيني المختلفة، بالإضافة إلى نصف عمره القصير. لذلك، فإن تطوير نظام توصيل الدواء المحتوي على داساتينيب، ذاتي الاستحلاب يمكن أن يساعد في التغلب على هذه المشكلات في علاج الخلايا السرطانية.
UNASSIGNED: تم تطوير تركيبات مختلفة لنظام توصيل الدواء ذاتي الاستحلاب ومحملة بداساتينيب باستخدام آيزوبروبيل ميريستات (مرحلة الزيت)، ولابرافيل (الخافض للتوتر السطحي)، والبولي إيثيلين جلايكول (الخافض للتوتر السطحي المشترك). تم تقييم الخواص الفيزيائية والكيميائية للتركيبات من حيث حجم القطرات، وكفاءة التغليف، وإطلاق الدواء في المختبر. تم أيضا تقييم السمية الخلوية للتركيبات على ثلاثة خطوط من الخلايا السرطانية، وسرطان القولون والمستقيم البشري وسرطان الثدي الغدي البشري، بالإضافة إلى خلايا الليفية الرئوية الجنينية البشرية الطبيعية من أجل الانتقائية.
UNASSIGNED: داساتينيب-تركيبة نظام توصيل الدواء ذاتي الاستحلاب، تتميز بحجم جسيم جيد، وكفاءة تغليف، وإطلاق دواء في المختبر. في فهمنا، أظهرت هذه الدراسة أن فعالية داساتينيب المضادة للسرطان - نظام الاستحلاب الذاتي، ونظام توصيل الدواء كان لها تأثيرات أفضل على السمية الخلوية على خطوط الخلايا السرطانية الثلاثة، وسرطان الثدي الغدي البشري، وسرطان القولون والمستقيم البشري، مقارنة مع داساتينيب النقي.
UNASSIGNED: من المحتمل أن تكون تركيبات نظام توصيل الدواء داساتينيب-الاستحلاب الذاتي، فعالة كطريقة مستدامة لتوصيل الدواء لعلاج السرطان.

Coenzyme Q10 (CoQ10) is an essential, lipid-soluble vitamin involved in electron transport in the oxidoreductive reactions of the mitochondrial respiratory chain. Structurally, the quinone ring is connected to an isoprenoid moiety, which has a high molecular weight. Over the years, coenzyme Q10 has become relevant in the treatment of several diseases, like neurodegenerative disorders, coronary diseases, diabetes, hypercholesterolemia, cancer, and others. According to studies, CoQ10 supplementation might be beneficial in the treatment of CoQ10 deficiencies and disorders associated with oxidative stress. However, the water-insoluble nature of CoQ10 is a major hindrance to successful supplementation. So far, many advancements in CoQ10 bioavailability enhancement have been developed using novel drug carriers such as solid dispersion, liposomes, micelles, nanoparticles, nanoemulsions, self-emulsifying drug systems, or various innovative approaches (CoQ10 complexation with proteins). This article aims to provide an update on methods to improve CoQ10 solubility and bioavailability.

The objectives of this study were to develop a self-emulsifying drug delivery system (SEDDS) to enhance the stability and efficacy of Cymbopogon citratus essential oil or lemongrass oil (LEO) against cattle tick larvae and engorged females. The system with the highest oil loading in SEDDS was composed of LEO (23.33%w/w), Tween 80: SGKH 4000 in a 2:1 ratio as surfactant (66.67%w/w), and propylene glycol as co-surfactant (10%w/w). The selected SEDDS-LEO has a particle size of 18.78 nm with a narrow size distribution (polydispersity index of 0.27). Notably, the stability of SEDDS was superior to that of the original oil, both during long-term storage and under accelerated conditions. SEDDS-LEO at oil concentrations ranging from 1.458% to 5.833% w/v showed a significantly higher percentage of egg-laying reduction against adult ticks compared with the original oil at the same concentrations (p < 0.05). Furthermore, SEDDS-LEO demonstrated greater larvicidal efficacy than the original oil, with lower LC50 and LC90 values of 0.91 mg/mL and 1.20 mg/mL, respectively, whereas the original oil\'s LC50 and LC90 values were 1.17 mg/mL and 1.74 mg/mL, respectively. Our findings indicate that SEDDS-LEO is a promising candidate for use as an acaricide in the control of tick populations in dairy cattle.

RN104 (2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole) is a thiazolylhydrazone derivative with prominent antifungal activity. This work aimed to develop a self-emulsifying drug delivery system (SEDDS) loaded with RN104 to improve its biopharmaceutical properties and enhance its oral bioavailability. Medium chain triglycerides, sorbitan monooleate, and polysorbate 80 were selected as components for the SEDDS formulation based on solubility determination and a pseudo-ternary phase diagram. The formulation was optimized using the central composite design in response surface methodology. The optimized condition consisted of medium chain triglycerides, sorbitan monooleate, and polysorbate 80 in a mass ratio of 65.5:23.0:11.5, achieving maximum drug loading (10 mg/mL) and minimum particle size (118.4 ± 0.7 nm). The developed RN104-SEDDS was fully characterized using dynamic light scattering, in vitro release studies, stability assessments, polarized light microscopy, and transmission electron microscopy. In vivo pharmacokinetic studies in mice demonstrated that RN104-SEDDS significantly improved oral bioavailability compared to free RN104 (the relative bioavailability was 2133 %). These results clearly indicated the successful application of SEDDS to improve the pharmacokinetic profile and to enhance the oral bioavailability of RN104, substantiating its potential as a promising antifungal drug candidate.

A self-emulsifying drug delivery system (SEDDS) containing long chain lipid digestion products (LDP) and surfactants was developed to increase solubility of two model weakly basic drugs, cinnarizine and ritonavir, in the formulation. A 1:1.2 w/w mixture of glyceryl monooleate (Capmul GMO-50; Abitec) and oleic acid was used as the digestion product, and a 1:1 w/w mixture of Tween 80 and Cremophor EL was the surfactant used. The ratio between LDP and surfactant was 1:1 w/w. Since the commercially available Capmul GMO-50 is not pure monoglyceride and contained di-and-triglycerides, the digestion product used would provide 1:2 stoichiometric molar ratio of monoglyceride and fatty acid after complete digestion in gastrointestinal fluid. Both cinnarizine and ritonavir had much higher solubility in oleic acid (536 and 72 mg/g, respectively) than that in glyceryl monooleate and glyceryl trioleate. Therefore, by incorporating oleic acid in place of glyceryl trioleate in the formulation, the solubility of cinnarizine and ritonavir could be increased by 5-fold and 3.5-fold, respectively, as compared to a formulation without the fatty acid. The formulation dispersed readily in aqueous media, and adding 3 mM sodium taurocholate, which is generally present in GI fluid, remarkably improved the dispersibility of SEDDS and reduced particle size of dispersions. Thus, the use of digestion products of long-chain triglycerides as components of SEDDS can enhance the drug loading of weakly basic compounds and increase dispersibility in GI fluids.

Due to its versatility in formulation and manufacturing, self-emulsifying drug delivery systems (SEDDS) can be used to design parenteral formulations. Therefore, it is necessary to understand the effects of excipients on the behavior of SEDDS formulations upon parenteral administration, particularly their interactions with blood plasma and cell membranes. In this study, we prepared three neutrally charged SEDDS formulations composed of medium-chain triglycerides as the oil phase, polyoxyl-35 castor oil (EL35) and polyethylene glycol (15)-hydroxystearate (HS15) as the nonionic surfactants, medium-chain mono- and diglycerides as the co-surfactant, and propylene glycol as the co-solvent. The cationic surfactant, didodecyldimethylammonium bromide (DDA), and the anionic surfactant, sodium deoxycholate (DEO), were added to the neutral SEDDS preconcentrates to obtain cationic and anionic SEDDS, respectively. SEDDS were incubated with human blood plasma and recovered by size exclusion chromatography. Data showed that SEDDS emulsion droplets can bind plasma protein to different extents depending on their surface charge and surfactant used. At pH 7.4, the least protein binding was observed with anionic SEDDS. Positive charges increased protein binding. SEDDS stabilized by HS15 can adsorb more plasma protein and induce more plasma membrane disruption activity than SEDDS stabilized by EL35. These effects were more pronounced with the HS15 + DDA combination. The addition of DDA and DEO to SEDDS increased plasma membrane disruption (PMD) activities, and DDA (1% w/w) was more active than DEO (2% w/w). PMD activities of SEDDS were concentration-dependent and vanished at appropriate dilution ratios.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are essential nutrients for human health and have been linked to a variety of health benefits, including reducing the risk of cardiovascular diseases. In this paper, a spray-dried powder formulation based on Pickering emulsions stabilized with cellulose nanocrystals (CNC) and hydroxypropyl methylcellulose (HPMC) has been developed. The formulation was compared in vitro and in vivo to reference emulsions (conventional Self-Emulsifying Drug Delivery System, SEDDS) to formulate n-3 PUFA pharmaceutical products, specifically in free fatty acid form. The results of in vivo studies performed in fasted dogs showed that Pickering emulsions reconstituted from powders are freely available (fast absorption) with a similar level of bioavailability as reference emulsions. In the studies performed with dogs in the fed state, the higher bioavailability combined with slower absorption observed for the Pickering emulsion, compared to the reference, was proposed to be the result of the protection of the n-3 PUFAs (in free fatty acid form) against oxidation in the stomach by the solid particles stabilizing the emulsion. This observation was supported by promising results from short-term studies of chemical stability of powders with n-3 PUFA loads as high as 0.8 g oil/g powder that easily regain the original emulsion drop sizes upon reconstitution. The present work has shown that Pickering emulsions may offer a promising strategy for improving the bioavailability and stability as well as providing an opportunity to produce environmentally friendly (surfactant free) and patient-acceptable solid oral dosage forms of n-3 PUFA in the free fatty acid form.

Leishmaniasis is a disease caused by protozoa species of the Leishmania genus, and the current treatments face several difficulties and obstacles. Most anti-leishmanial drugs are administered intravenously, showing many side effects and drug resistance. The discovery of new anti-leishmanial compounds and the development of new pharmaceutical systems for more efficient and safer treatments are necessary. Copaiba oil-resin (CO) has been shown to be a promising natural compound against leishmaniasis. However, CO displays poor aqueous solubility and bioavailability. Self-emulsifying drug delivery systems (SEDDS) can provide platforms for release of hydrophobic compounds in the gastrointestinal tract, improving their aqueous solubilization, absorption and bioavailability. Therefore, the present work aimed to develop SEDDS containing CO and Soluplus® surfactant for the oral treatment of leishmaniasis. The design of the systems was accomplished using ternary phase diagrams. Emulsification and dispersion time tests were used to investigate the emulsification process in gastric and intestinal environments. The formulations were nanostructured and improved the CO solubilization. Their in vitro antiproliferative activity against promastigote forms of L. amazonensis and L. infantum, and low in vitro cytotoxicity against macrophages were also observed. More studies are necessary to determine effectiveness of SOL in these systems, which can be candidates for further pharmacokinetics and in vivo investigations.

UNASSIGNED: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug.
UNASSIGNED: Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product.
UNASSIGNED: Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products.
UNASSIGNED: The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow.
UNASSIGNED: Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (p < 0.05).

For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive in vivo outcomes of this formulation strategy, self-emulsifying drug delivery systems (SEDDSs) have been intensively studied in the last few years as a way of overcoming the different challenges associated with the oral delivery of macromolecules. The purpose of the present study was to examine the possibility of developing solid SEDDSs as potential carriers for the oral delivery of lysozyme (LYS) using the Quality by Design (QbD) concept. LYS was successfully ion paired with anionic surfactant, sodium dodecyl sulphate (SDS), and this complex was incorporated into a previously developed and optimized liquid SEDDS formulation comprising medium-chain triglycerides, polysorbate 80, and PEG 400. The final formulation of a liquid SEDDS carrying the LYS:SDS complex showed satisfactory in vitro characteristics as well as self-emulsifying properties (droplet size: 13.02 nm, PDI: 0.245, and zeta potential: -4.85 mV). The obtained nanoemulsions were robust to dilution in the different media and highly stable after 7 days, with a minor increase in droplet size (13.84 nm) and constant negative zeta potential (-0.49 mV). An optimized liquid SEDDS loaded with the LYS:SDS complex was further solidified into powders by adsorption onto a chosen solid carrier, followed by direct compression into self-emulsifying tablets. Solid SEDDS formulations also exhibited acceptable in vitro characteristics, while LYS preserved its therapeutic activity in all phases of the development process. On the basis of the results gathered, loading the hydrophobic ion pairs of therapeutic proteins and peptides to solid SEDDS may serve as a potential method for delivering biopharmaceuticals orally.