Liposomal propranolol for treatment of infantile hemangioma at compounding pharmacies.

Infantile hemangiomas (IH) are common benign soft tissue tumors, frequently affecting infants. While Propranolol Hydrochloride (Pro HCl) has emerged as a promising treatment for IH, its topical application remains challenging due to the need for stable and efficacious carriers. This study investigates the potential of preformulated liposomes as carriers for topical delivery of Pro HCl for the treatment of IH in compounding pharmacies. Liposomes loaded with Pro HCl were prepared using active pharmaceutical ingredient or commercially available propranolol tablets and various dilution media, including Water for Injection (WFI), Dextrose 5%, and NaCl 0.9%. The physicochemical properties of the liposomal formulations (Pro HCl content, encapsulation efficiency, loading capacity, and colloidal stability) were assessed over a 90-day storage at 4 °C. In vitro release kinetics and transdermal permeation of Pro HCl from liposomes were also evaluated. Liposome properties were influenced by the dilution medium. Pro HCl content remained stable in liposomes encapsulating API (Lipo-Pro), regardless of the dilution medium. Lipo-Pro showed sustained drug release over time, suggesting its potential for maintaining therapeutic levels. Pro HCl exhibited enhanced transdermal permeability from Lipo-Pro compared to aqueous solution, indicating its potential for topical IH treatment. Preformulated liposomes offer a stable and effective carrier for Pro HCl, potentially suitable for extemporaneous preparations in compounding pharmacies. Their enhanced transdermal permeability presents a promising alternative for topical IH treatment. This study provides valuable insights into the development of innovative and effective drug delivery strategies for managing IH, with future research focusing on in vivo applications and therapeutic potential.

Measurements of liposome biomechanical properties by combining line optical tweezers and dielectrophoresis.

Liposomes are well-known cell simulators and are currently studied as drug delivery systems, for a targeted delivery of higher drug concentrations, in specific cells. Novel biophotonic techniques for manipulation and characterization of liposomes have been developed; among which are optical tweezers. In our work, we demonstrate a novel use of line optical tweezers to manipulate and cause liposome deformations. Optical forces induce tension on liposomes, which are stretched along the line optical trap. The method of dielectrophoresis, combined with optical tweezers, was used to measure the exerted optical forces. As a consequence, in the case of reversible liposome deformations, the value of the shear and bending moduli of liposomes was calculated. We anticipate that the selective manipulation of liposomes will help us toward a better understanding of the cellular-liposome interactions. Studying the biomechanical properties of liposomes will provide an insight into the mechanical behavior of individual living cells, which have recently been implicated in many aspects of human physiology and patho-physiology. The biomechanical properties of cells (i.e. deformability, stiffness and elasticity) can be useful biomarkers for various disease processes and changes of the cell state.

Caveolar uptake and endothelial-protective effects of nanostructured lipid carriers in acid aspiration murine acute lung injury.

PURPOSE: Nanostructured lipid carriers (NLC), nanosized phospholipids/triglyceride particles developed for drug delivery, are considered biologically inactive. We assessed the efficacy of unloaded NLC as experimental treatment for acute lung injury (ALI). METHODS: To induce ALI, C57Black/6 male mice received intratracheal injections of HCl or saline; A single dose of 16 mg/Kg NLC or saline was injected intravenously concomitantly with HCl challenge. NLC uptake mechanisms and effects on endothelial permeability and signaling were studied in cultured endothelial cells and neutrophils. RESULTS: NLC pre-treatment attenuated pulmonary microvascular protein leak, airspace inflammatory cells, thrombin proteolytic activity and histologic lung injury score 24 h post insult. Using fluorescence measurements and flow cytometry in mouse lung microvascular endothelial cell culture homogenates, we determined that NLC rendered fluorescent by curcumin labeling are taken up by endothelial cells from mice expressing caveolin-1, the coat protein of caveolar endocytic vesicles, but not from caveolin-1 gene-disrupted mice, which lack caveolae. In contrast, conventional emulsions (CE), consisting of larger particles, were not incorporated. In addition, NLC pre-treatment of cultured human lung microvascular endothelial cells abrogated thrombin-induced activation of p44/42, albumin permeability response, actin cytoskeletal remodeling and interleukin-6 production. Finally, NLC but not CE abrogated lipopolysaccharide-triggered interleukin-8 release. CONCLUSIONS: NLC are engulfed by endothelial caveolae and possess endothelial-protective effects. These novel properties may be of potential utility in ALI.

Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis: Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs.

Nonalcoholic steatohepatitis (NASH) is the most severe manifestation of nonalcoholic fatty liver disease (NAFLD), a common complication of type 2 diabetes, and may lead to cirrhosis and hepatocellular carcinoma. Oxidative stress and liver cell damage are the major triggers of the severe hepatic inflammation that characterizes NASH, which is highly correlated with atherosclerosis and coronary artery disease. Regarding drug therapy, research on the role of GLP-1 analogues and DPP4 inhibitors, novel classes of antidiabetic drugs, is growing. In this review, we outline the association between NASH and atherosclerosis, the underlying molecular mechanisms, and the effects of incretin-based drugs, especially GLP-1 RAs, for the therapeutic management of these conditions.

Anti-Quorum-Sensing Potential of Ethanolic Extracts of Aromatic Plants from the Flora of Cyprus.

Quorum sensing (QS) is a form of intra- and inter-species communication system employed by bacteria to regulate their collective behavior in a cell population-dependent manner. QS has been implicated in the virulence of several pathogenic bacteria. This work aimed to investigate the anti-QS potential of ethanolic extracts of eight aromatic plants of Cyprus, namely, Origanum vulgare subsp. hirtum, Rosmarinus officinalis, Salvia officinalis, Lavendula spp., Calendula officinalis, Melissa officinalis, Sideritis cypria, and Aloysia citriodora. We initially assessed the effects of the extracts on autoinducer 2 (AI-2) signaling activity, using Vibrio harveyi BB170 as a reported strain. We subsequently assessed the effect of the ethanolic extracts on QS-related processes, including biofilm formation and the swarming and swimming motilities of Escherichia coli MG1655. Of the tested ethanolic extracts, those of Origanum vulgare subsp. hirtum, Rosmarinus officinalis, and Salvia officinalis were the most potent AI-2 signaling inhibitors, while the extracts from the other plants exhibited low to moderate inhibitory activity. These three ethanolic extracts also inhibited the biofilm formation (>60%) of E. coli MG1655, as well as its swimming and swarming motilities, in a concentration-dependent manner. These extracts may be considered true anti-QS inhibitors because they disrupt QS-related activities of E. coli MG1655 without affecting bacterial growth. The results suggest that plants from the unexplored flora of Cyprus could serve as a source for identifying novel anti-QS inhibitors to treat infectious diseases caused by pathogens that are resistant to antibiotics.

Exploitation of traditional healing properties, using the nanotechnology's advantages: The case of curcumin.

Curcumin (CUR) has a long history of use as an antimicrobial, anti-inflammatory and wound healing agent, for the treatment of various skin conditions. Encapsulation in nanocarriers may overcome the administration limitations of CUR, such as lipophilicity and photodegradation. Lipid nanocarriers with different matrix fluidity (Solid Lipid Nanoparticles; SLN, Nanostructured Lipid Carriers; NLC, and Nanoemulsion; NE) were prepared for the topical delivery of curcumin (CUR). The occlusive properties and film forming capacity, as well as the release profile of incorporated CUR, its protection against photodegradation and wound healing were studied in vitro, using empty nanocarriers or free CUR as control. The results suggest that incorporation of CUR in nanocarriers offers a significant protection against photodegradation that is not influenced by the matrix fluidity. However, this characteristic regulates properties such as the occlusion, the release rate and wound healing ability of CUR. Nanoparticles of low fluidity provided better surface occlusion, film forming capacity and retention of the incorporated CUR. All nanocarriers but especially NLC, achieved faster wound healing at lower dose of incorporated CUR. In conclusion, nanotechnology may enhance the action of CUR against skin conditions. Important characteristics of the nanocarrier such as matrix fluidity should be taken into consideration in the design of CUR nanosystems of optimal efficiency.

Development and characterization of oligonucleotide-tagged dye-encapsulating EPC/DPPG liposomes.

Liposomes applications in health care include meanly their ability to carry drugs and genes inside the human body for therapeutic purposes. Nevertheless their applicability can extend far beyond and could be used as analytical tools in order to perform rapid, low-cost, sensitive and specific analyses. Their physical characteristics, such as large internal volume and extended surface area, render them ideal for these applications and specifically for improving the specificity and sensitivity of the analytical assay. The purpose of this study was to develop a simple, stable and low-cost oligonucleotide-tagged liposomal formulation consisting of EggPC and DPPG with a simple to synthesize thiol-reactive conjugate (Mal-SA) incorporated into the lipid bilayer of liposomes. The prepared liposomes, having also the water soluble dye Sulforhodamine B encapsulated in their inner cavity, were characterized in terms of their physicochemical (size, size distribution, zeta-potential, lipid content) and mechanical (morphology, rigidity) properties. The results showed that the final liposomal formulation could be used in the future as analytical tool for detecting pathogen strains of microorganism in biological milieu.

Type and location of interaction between hyperbranched polymers and liposomes. Relevance to design of a potentially advanced drug delivery nanosystem (aDDnS).

Advanced drug delivery nanosystems (aDDnSs) combining liposomal and dendritic materials have only recently appeared in the research field of drug delivery. The nature and localization of the interactions between the components of such systems are not yet fully described. In this study, liposomes are combined with hyperbranched polyesters for the development of new aDDnSs. The polymer-lipid interactions along with their dependence on the polyesters pseudogeneration number and the liposomal lipid composition have been examined. The results indicate that the interaction between the materials takes place in the headgroup region, where H-bonds between the polymers terminal hydroxyls and the phospholipids phosphate moiety are formed. Due to the polymers' compact imperfect structure, which varies with pseudogeneration number, no linear trends are observed with increasing pseudogeneration number. Moreover, it is shown that high percentages of cholesterol in the lipid bilayer affect the penetration of the polymers in the headgroup region.

Atomic force microscopy: a tool to study the structure, dynamics and stability of liposomal drug delivery systems.

Much work has been done during the past few decades to develop effective drug delivery systems (DDS), many of which are based on nanotechnology science. Liposomes are the most attractive lipid vesicles for drug delivery. The multifunctional properties of liposomes have a key role in modifying the bioavailability profile of a therapeutic agent. Different analytical techniques can be used to describe liposomes, not least applied scanning probe microscopy (SPM) techniques. Atomic force microscopy (AFM) seems to be one of the most effectively applied SPM techniques. This review article outlines the applications of AFM in evaluating the physical characteristics and stability of liposomal DDSs. Other well-known microscopy techniques used in evaluating liposome physical characteristics are also mentioned, and the contribution of AFM to evaluating liposomal stability is discussed. Among the advantages of AFM in examining the physicochemical properties of liposomal DDSs is its ability to provide morphological and metrology information on liposome properties. AFM thus appears to be a promising tool in technological characterization of liposomal DDSs.