Liposomes is a non-viral vector drug delivery system. Nevertheless, the existing commercial liposomes are quite expensive and not always affordable, particularly in developing countries. To address this challenge, plant-derived nanoparticles offer a cost-effective alternative while maintaining similar drug delivery capabilities. Hence, this study aimed to explore the potential of nanovesicles derived from black cumin (Nigella sativa) as a miRNA delivery system. Gradient sucrose-centrifugation was utilized to separate the nanovesicles derived from black cumin. Subsequently, these isolated nanovesicles, originating from black cumin, underwent centrifugation at a speed of 11,000 rpm. The miRNAs were encapsulated within these nanovesicles through the ethanol injection method. Morphological examinations of the nanovesicles derived from black cumin and DOTAP, as the positive control, were conducted using TEM and SEM. Furthermore, the cytotoxicity of the nanovesicles derived from black cumin was evaluated through the MTT assay on the MCF-7 cell line. Lastly, the process of internalization for both the black cumin-derived nanovesicles and DOTAP was visualized using a confocal microscope. Results demonstrated the successful isolation of nanovesicles from black cumin using the sucrose gradient method. These particles exhibited a spherical shape with diameters ranging from 100 nm to 200 nm, featuring a negative surface charge. When MCF-7 cells were exposed to black cumin-derived nanovesicles at a concentration of 12 mg/mL, cell viability reached 89.8 %, showing no significant difference compared to the positive control (p > 0.05). Furthermore, the MCF-7 cell line effectively internalized the black cumin-derived nanovesicles after a 45-minute incubation period. Notably, the encapsulation of miRNA within these nanovesicles demonstrated an impressive entrapment efficiency of 76.4 %. Subsequent transfection of miRNA-loaded black cumin-derived nanovesicles resulted in a substantial inhibition of MCF-7 cell viability, reducing it to 67 % after 48 h of treatment. These findings underscore the potential of black cumin-derived nanovesicles as potential nanovectors for the encapsulation and delivery of miRNA within drug delivery systems, offering a cost-effective and accessible solution for advanced drug delivery technologies, particularly in developing country.

The aim of this study was to develop azithromycin (AZT)-loaded liposomes (LP) and niosomes (NS) useful for the treatment of bacterial skin infections and acne. LP based on phosphatidylcholine from egg yolk (EPC) or from soybean lecithin (SPC), and NS composed of sorbitan monopalmitate (Span 40) or sorbitan monostearate (Span 60) were prepared through the thin film hydration (TFH) and the ethanol injection (EI) methods. The formulations were subsequently characterized for their physico-chemical and functional properties. Vesicles prepared through TFH showed higher average sizes than the corresponding formulations obtained by EI. All the vesicles presented adequate encapsulation efficiency and a negative ζ potential, which assured good stability during the storage period (except for LP-SPC). Formulations prepared with TFH showed a more prolonged AZT release than those prepared through EI, due to their lower surface area and multilamellar structure, as confirmed by atomic force microscopy nanomechanical characterization. Finally, among all the formulations, NS-Span 40-TFH and LP-EPC-TFH allowed the highest drug accumulation in the skin, retained the antimicrobial activity and did not alter fibroblast metabolism and viability. Overall, they could ensure to minimize the dosing and the administration frequency, thus representing promising candidates for the treatment of bacterial skin infections and acne.

The left ventricular summit is a site of origin for idiopathic ventricular arrhythmias. With advancements in mapping and ablation techniques, sites previously considered inaccessible can now be approached. Anatomical knowledge of the 3-dimensional landmarks of this space is important, as critical structures reside within its boundaries and are potentially liable to collateral injury during ablation. This article reviews reported complications from ablation of ventricular arrhythmias arising from the left ventricular summit and its vicinity and discusses the pros and cons of different ablation technique and the role of an individualized anatomical approach to reduce procedural related complications and improve outcomes.

OBJECTIVE: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy.
METHODS: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as \"critical\" and \"important\" were considered in the systematic review of evidence and only those classified as \"critical\" were considered in the formulation of recommendations.
RESULTS: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists.
CONCLUSIONS: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.

Intrauterine adhesion (IUA), a leading cause of uterine infertility, is characterized by endometrial fibrosis. Implementing an appropriate animal model is essential for the research on the mechanisms of IUA. In the present study, we established and evaluated different intrauterine adhesion modeling procedures in rats to provide a reference for researchers. Rat IUA models were established by mechanical injury, 95% ethanol injection, and dual (mechanical injury with infection) injury. After two estrus cycles, the female rats were mated with sexually mature male rats, and uterine tissues were obtained on the 5th day of pregnancy. Hematoxylin and eosin staining and immunohistochemical detection of cytokeratin 19 and vimentin were performed to assess the morphology of the endometrium. Masson\'s trichrome staining and the expression of transforming growth factor-β1 and collagen I were used to assess the endometrium fibrosis. The expression of integrin avβ3, leukemia inhibitory factor, and homeobox gene A10 in the rat endometrium was used to evaluate the endometrial receptivity. In addition, the efficiency of embryo implantation was examined in the uterus on the 8th day of pregnancy. Our study found that mechanical injury caused by a curette can be completely repaired after two estrus cycles. However, dual injury and 95% ethanol injection can be used to establish an IUA rat model, and the dual injury is closer to the clinicpathological characteristics of IUA.

The metal complex copper diethyldithiocarbamate (CuET) induces cancer cell death by inhibiting protein degradation and induces proteotoxic stress, making CuET a promising cancer therapeutic. However, no clinical formulation of CuET exists to date as the drug is insoluble in water and exhibits poor bioavailability. To develop a scalable formulation, nanoliposomal (LP) CuET was synthesized using ethanol injection as a facile one-step method that is suitable for large-scale manufacturing. The nanoparticles are monodispersed, colloidally stable, and approximately 100 nm in diameter with an encapsulation efficiency of over 80%. LP-CuET demonstrates excellent stability in plasma, minimal size change, and little drug release after six-month storage at various temperatures. Additionally, melanoma cell lines exhibit significant sensitivity to LP-CuET and cellular uptake occurs predominantly through endocytosis in YUMM 1.7 cancer cells. Intracellular drug delivery is mediated by vesicle acidification with more nanoparticles being internalized by melanoma cells compared with RAW 264.7 macrophages. Additionally, the nanoparticles preferentially accumulate in YUMM 1.7 tumors where they induce cancer cell death in vivo. The development and characterization of a stable and scalable CuET formulation illustrated in this study fulfils the requirements needed for a potent clinical grade formulation.

A continuous polymeric micelle processing platform was successfully developed, which eliminated batch-to-batch variation in critical quality attributes (for example, size and polydispersity that are typically associated with batch processing). A continuous precipitation process was achieved via coaxial turbulent jet in co-flow technology allowing precise control of particle size with average particle size in the range 15 to 70 nm and low polydispersity. Critical relationships between material attributes (e.g., block copolymer design), process parameters (e.g., polymer concentration, organic to aqueous flow rate ratios, and temperature), and critical quality attributes (e.g., size and polydispersity) of the polymeric micelles were realized via multiple designs of experiments studies. Both polymer molecular weight and concentration were shown to influence the micelle polydispersity index. Notably, higher molecular weight polymer required higher processing temperatures to produce monodispersed particles and were generally of larger size. Using optimized conditions, paclitaxel polymeric micelles that are qualitatively and quantitatively equivalent to commercial Genexol PM were produced, exhibiting comparable quality attributes including particle size, size distribution, morphology, drug loading, release characteristics, and stability. Lastly, a dynamic light scattering method was adapted to determine the critical micelle concentration and aggregation number of the block copolymers, providing useful information about the raw material.

An understanding of the factors that affect liposome size, drug loading, stability and drug release is critical for the rational design of liposomes with desired pharmacokinetics and biodistribution. This article presents a report on the formulation and characterization of BIIB093 (glibenclamide) liposomes as well as a detailed analysis of the influence of formulation methods and parameters on encapsulation efficiency, liposome size, charge (zeta potential, ZP), polydispersity index (PDI), and drug release. PEGylated liposomes containing BIIB093 were made using ethanol injection and calcium acetate remote loading. The critical formulation parameters investigated include: the effect of lipid chain length, lipid unsaturation, lipid phase transition temperature (Tc) and the amount of cholesterol. Liposomes generated in this study had low average particle size (130 ± 20 nm), PDI (0.15 ± 0.1) and ZP (-2 ± 1 mV). Liposomes made from lipids with long acyl chains showed enhanced drug loading, encapsulation efficiency and drug retention. Similarly, liposomes made from lipids with high degree of unsaturation and low Tc exhibited faster drug release rates. Additionally, increasing the amount of cholesterol in the liposome bilayer improved PDI, decreased drug incorporation and accelerated drug release but had negligible impact on liposome size and ZP. Furthermore, encapsulating the drug in the liposome core enabled sustained drug release.

Ultrasound-guided percutaneous ethanol ablation procedures for locoregional recurrences in papillary thyroid carcinoma (PTC) can be repeatedly performed over years. Skin metastases (SM) from PTC generally portend a lethal prognosis. Our patient case report demonstrates the innovative use in low-risk PTC (LRPTC) of treatment modalities designed to prevent neck re-explorations and capable of eliminating both locoregional recurrences and SM. In 2004, a 48-year-old man presented with neck nodal metastases due to PTC. He underwent a near-total thyroidectomy and nodal dissection, confirming an 8-mm PTC involving 2 ipsilateral node metastases. Postoperatively, he received 2 doses of radioactive iodine (RAI) for remnant uptake (cumulative dose 338 mCi); posttherapy scanning was unrevealing. In 2007, he underwent right neck dissection for further node metastases. In 2008, a guided biopsy confirmed a level IV node metastasis. He was referred to our institution for ethanol ablation. Two node metastases were ablated and subsequently disappeared. During 2010-2016, he developed an additional 6 node metastases, which were treated with ethanol ablation; all disappeared on high-resolution sonography. FDG-PET-CT scans in 2009 and 2016 were negative for distant spread. In 2016, a SM in his right neck was removed by dermatologic surgery. In 2017-2018, 2 further SM were excised with negative margins, one after Mohs surgery. He has now been disease-free for 20 months. In conclusion, despite 3 neck surgeries and 2 RAI therapies, our patient repeatedly developed both locoregional recurrences and SM. All 11 disease foci were eliminated with minimally invasive procedures which should more often be considered as effective treatment options in LRPTC.

The purpose of this investigation was to encapsulate carvedilol, a model beta-blocker antihypertensive into nano-spanlastics, followed by incorporation into 1% CMC wafer to afford a mucoadhesive buccal drug delivery system, targeting to sidestep the first-pass metabolism, improving the drug absorption and pharmacological effect, achieving non-invasive buccal delivery for treating hypertension. Carvedilol-loaded nano-spanlastics were rendered by ethanol injection technique, using 23 factorial design. The effect of formulation variables was investigated on nano-spanlastic characteristics. The optimal nano-spanlastic formulation (S2; containing 20% Brij 97) exhibited particle size (239.8 ± 5 nm), entrapment efficiency (98. 16 ± 1.44%), deformability index (8.74 ± 0.42 g), and the flux after 24 h (Jmax) (22.5 ± 0.25 (μg/cm2/h) with enhancement ratio 2.87 as well as excellent stability after storage. Permeation study verified the preeminence of the S2 formula. A confocal laser scanning microscope showed deep penetration of S2 through sheep buccal mucosa formula compared to rhodamine B solution. S2-based wafer showed acceptable characters (pH, swelling, drug content, residence time, and release rate). In vivo studies (pharmacodynamic study and biochemical evaluation) showed considerable improvement in blood pressure, the profile of the lipid, oxidant stress biomarkers, and cardiac markers. Histopathological studies revealed the superiority of S2 wafer in the protection of heart tissues over Carvid®. The results achieved indicate that nano-spanlastic-based wafer offers a promising improving trans-buccal carvedilol delivery system. Graphical abstract.