Recent advances in nanosystems and strategies for vaginal delivery of antimicrobials

Vaginal infections such as bacterial vaginosis (BV), chlamydia, gonorrhea, genital herpes, candidiasis, and trichomoniasis affect millions of women each year. They are caused by an overgrowth of microorganisms, generally sexually transmitted, which in turn can be favored by alterations in the vaginal flora. Conventional treatments of these infections consist in systemic or local antimicrobial therapies. However, in the attempt to reduce adverse effects and to contrast microbial resistance and infection recurrences, many efforts have been devoted to the development of vaginal systems for the local delivery of antimicrobials. Several topical dosage forms such as aerosols, lotions, suppositories, tablets, gels, and creams have been proposed, although they are sometimes ineffective due to their poor penetration and rapid removal from the vaginal canal. For these reasons, the development of innovative drug delivery systems, able to remain in situ and release active agents for a prolonged period, is becoming more and more important. Among all, nanosystems such as liposomes, nanoparticles (NPs), and micelles with tunable surface properties, but also thermogelling nanocomposites, could be exploited to improve local drug delivery, biodistribution, retention, and uptake in vulvovaginal tissues. The aim of this review is to provide a survey of the variety of nanoplatforms developed for the vaginal delivery of antimicrobial agents. A concise summary of the most common vaginal infections and of the conventional therapies is also provided

Assessment of in‐situ gelling microemulsion systems upon temperature and dilution condition for corneal delivery of bevacizumab

Bevacizumab (BVZ), a recombinant humanized monoclonal antibody, has recently been proposed as a topical application in the treatment of anterior segment neovascularization; however, as there are some disadvantages in the administration of common eye-drops, ophthalmic topical drug delivery systems are under study to improve the precorneal residence time, reducing the frequency of administration. In this work, oil-in-water and water-in-oil BVZ-loaded microemulsions are developed, able to increase their viscosity, either by the formation of a liquid-crystalline structure upon aqueous dilution, thanks to the presence of Epikuron® 200 and polysorbate 80, or by body-temperature-induced jellification for the presence of Pluronic® F127 aqueous solution as an external phase. In oil-in-water microemulsion, hydrophobic ion pairs of BVZ were also prepared, and their incorporation was determined by release studies. Microemulsions were characterized for rheological behavior, corneal opacity, in vitro corneal permeation, and adhesion properties. The studied microemulsions were able to incorporate BVZ (from 1.25 to 1.6 mg/mL), which maintained dose-dependent activity on retinal pigment epithelial ARPE-19 cell lines. BVZ loaded in microemulsions permeated the excised cornea easier (0.76–1.56% BVZ diffused, 4–20% BVZ accumulated) than BVZ commercial solution (0.4% BVZ diffused, 5% accumulated) and only a mild irritation effect on the excised cornea was observed. The good adhesion properties as well the increased viscosity after application, under conditions that mimic the corneal environment (from 1 × 103 to more than 100 × 103 mPa·s), might prolong precorneal residence time, proving these systems could be excellent topical BVZ release systems

Developing actively targeted nanoparticles to fight cancer: Focus on italian research

Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles to direct drugs towards different receptors that are overexpressed on cancer cells or in the tumor microenvironment. In particular, the review discusses polymeric nanocarriers, liposomes, lipoplexes, niosomes, solid lipid nanoparticles, squalene nanoassemblies and nanobubbles. For each nanocarrier, the main ligands, conjugation strategies and target receptors are described. The literature indicates that polymeric nanoparticles and liposomes stand out as key tools for improving specific drug delivery to the site of action. In addition, solid lipid nanoparticles, squalene nanoparticles and nanobubbles have also been successfully proposed. Taken together, these strategies all offer many platforms for the design of nanocarriers that are suitable for future clinical translation

Exploiting lipid and polymer nanocarriers to improve the anticancer sonodynamic activity of chlorophyll

Sonodynamic therapy is an emerging approach that uses low-intensity ultrasound to activate a sonosensitizer agent triggering its cytotoxicity for selective cancer cell killing. Several molecules have been proposed as sonosensitizer agents, but most of these, as chlorophyll, are strongly hydrophobic with a low selectivity towards cancer tissues. Nanocarriers can help to deliver more efficiently the sonosensitizer agents in the target tumor site, increasing at the same time their sonodynamic effect, since nanosystems act as cavitation nuclei. Herein, we propose the incorporation of unmodified plant-extracted chlorophyll into nanocarriers with different composition and structure (i.e., liposomes, solid lipid nanoparticles and poly(lactic-co-glycolic acid) nanoparticles) to obtain aqueous formulations of this natural pigment. The nanocarriers have been deeply characterized and then incubated with human prostatic cancer cells (PC-3) and spheroids (DU-145) to assess the influence of the different formulations on the chlorophyll sonodynamic effect. The highest sonodynamic cytotoxicity was obtained with chlorophyll loaded into poly(lactic-co-glycolic acid) nanoparticles, showing promising results for future clinical investigations on sonodynamic therapy

Nanoparticles Based on Fructose and Alkaly-Earth Halogenides with Second Harmonic Generation properties for applications as bio-sensors and for Radiotherapy

In recent years, some Metal Organic Frameworks with Second Harmonic Generation (SHG) properties, based on fructose and alkali-earth alogenides, were investigated to understand the effect of cation size and anion polarizability on crucial quantities correlated to the non-linear optical (NLO) response, such as hyperpolarizability and optical susceptibility [1,2]. The compounds studied are interesting for biomedicine applications, as they combine high biocompatibility, due to their non-toxic components, and significant SH emission, that can permit exploitation for in vitro bio-imaging. Right now, a possible application in radiotherapy is under investigation. To these purposes we synthetized nanoparticles of some MOFs, based on fructose and SrX2 salts (X=Cl, I). The compounds were characterized by single-crystal and powder XRD, IR and RAMAN spectroscopy and the second-order susceptibility were estimated from theoretical calculations, both in vacuo and in the solid state. Furthermore, we attempted to assess the reduction of the SH intensity for small quantities of nano-crystals, in order to ascertain the possibility of applications in biological systems. The nanoparticles were encapsulated in a phospholipidic shell and preliminary activity studies on target cells are in progress. [1] D. Marabello, P. Antoniotti, P. Benzi, C. Canepa, E. Diana, L. Operti, L. Mortati, M. P. Sassi J. Mater. Sci., 2015, 50 (12), 4330- 4341 [2] D. Marabello, P. Antoniotti, P. Benzi, C. Canepa, L. Mortati, M. P. Sassi Acta Cryst. B, accepte

Characterisation and Skin Distribution of Lecithin-Based Coenzyme Q10-Loaded Lipid Nanocapsules

The purpose of this study was to investigate the influence of the inner lipid ratio on the physicochemical properties and skin targeting of surfactant-free lecithin-based coenzyme Q10-loaded lipid nanocapsules (CoQ10-LNCs). The smaller particle size of CoQ10-LNCs was achieved by high pressure and a lower ratio of CoQ10/GTCC (Caprylic/capric triglyceride); however, the zeta potential of CoQ10-LNCs was above /− 60 mV/ with no distinct difference among them at different ratios of CoQ10/GTCC. Both the crystallisation point and the index decreased with the decreasing ratio of CoQ10/GTCC and smaller particle size; interestingly, the supercooled state of CoQ10-LNCs was observed at particle size below about 200 nm, as verified by differential scanning calorimetry (DSC) in one heating–cooling cycle. The lecithin monolayer sphere structure of CoQ10-LNCs was investigated by cryogenic transmission electron microscopy (Cryo-TEM). The skin penetration results revealed that the distribution of Nile red-loaded CoQ10-LNCs depended on the ratio of inner CoQ10/GTCC; moreover, epidermal targeting and superficial dermal targeting were achieved by the CoQ10-LNCs application. The highest fluorescence response was observed at a ratio of inner CoQ10/GTCC of 1:1. These observations suggest that lecithin-based LNCs could be used as a promising topical delivery vehicle for lipophilic compounds

The calming effect of a new wearable device during the anticipation of public speech

We assessed the calming effect of doppel, a wearable device that delivers heartbeat-like tactile stimulation on the wrist. We tested whether the use of doppel would have a calming effect on physiological arousal and subjective reports of state anxiety during the anticipation of public speech, a validated experimental task that is known to induce anxiety. Two groups of participants were tested in a single-blind design. Both groups wore the device on their wrist during the anticipation of public speech, and were given the cover story that the device was measuring blood pressure. For only one group, the device was turned on and delivered a slow heartbeat-like vibration. Participants in the doppel active condition displayed lower increases in skin conductance responses relative to baseline and reported lower anxiety levels compared to the control group. Therefore, the presence, as opposed to its absence, of a slow rhythm, which in the present study was instantiated as an auxiliary slow heartbeat delivered through doppel, had a significant calming effect on physiological arousal and subjective experience during a socially stressful situation. This finding is discussed in relation to past research on responses and entrainment to rhythms, and their effects on arousal and mood