Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5–10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKKα-β/NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

Bone diseases include a wide group of skeletal-related disorders that cause mobility limitations and mortality. In some cases, e.g., in osteosarcoma (OS) and metastatic bone cancer, current treatments are not fully effective, mainly due to low patient compliance and to adverse side effects. To overcome these drawbacks, nanotechnology is currently under study as a potential strategy allowing specific drug release kinetics and enhancing bone regeneration. Polymers, ceramics, semiconductors, metals, and self-assembled molecular complexes are some of the most used nanoscale materials, although in most cases their surface properties need to be tuned by chemical or physical reactions. Among all, scaffolds, nanoparticles (NPs), cements, and hydrogels exhibit more advantages than drawbacks when compared to other nanosystems and are therefore the object of several studies. The aim of this review is to provide information about the current therapies of different bone diseases focusing the attention on new discoveries in the field of targeted delivery systems. The authors hope that this paper could help to pursue further directions about bone targeted nanosystems and their application for bone diseases and bone regeneration.

Background: Solid lipid nanoparticles (SLNs) are attractive drug delivery systems for lipophilic molecules like curcumin (CURC) with low chemical stability. Methods: A simple, innovative, and cold-operating method, named “cold dilution of microemulsion” is developed by the authors to produce SLNs. An oil-in-water microemulsion (µE), whose disperse phase consisted of a solution of trilaurin in a partially water-miscible solvent, was prepared after mutually saturating solvent and water. Trilaurin SLNs precipitated following solvent removal upon water dilution of the µE. After SLN characterization (mean size, Zeta potential, CURC entrapment efficiency, and over time stability), they were tested for in vitro cytotoxicity studies on pancreatic adenocarcinoma cell lines and for in vivo preliminary biodistribution studies in Wistar healthy rats. Results: CURC loaded SLNs (SLN-CURC) had mean diameters around 200 nm, were negatively charged, stable over time, and able to entrap CURC up to almost 90%, consequently improving its stability. SLN-CURC inhibited in vitro pancreatic carcinoma cell growth in concentration-dependent manner. Their in vivo intravenous administration suggested a possible long circulation. Conclusions: These results, according to a concomitant study on chitosan-coated SLNs, confirm the possibility to apply the developed SLN-based delivery systems as a means to entrap CURC, to improve both its water dispersibility and chemical stability, facilitating its application in therapy.

The bioavailability of ophthalmic therapeutics is reduced because of the presence of physiological barriers whose primary function is to hinder the entry of exogenous agents, therefore also decreasing the bioavailability of locally administered drugs. Consequently, repeated ocular administrations are required. Hence, the development of drug delivery systems that ensure suitable drug concentration for prolonged times in different ocular tissues is certainly of great importance. This objective can be partially achieved using thermosensitive drug delivery systems that, owing to their ability of changing their state in response to temperature variations, from room to body temperature, may increase drug bioavailability. In the case of topical instillation, in situ forming gels increase pre-corneal drug residence time as a consequence of their enhanced adhesion to the corneal surface. Otherwise, in the case of intraocular and periocular, i.e., subconjunctival, retrobulbar, peribulbar administration, among others, they have the undoubted advantage of being easily injectable and, owing to their sudden thickening at body temperature, have the ability to form an in situ drug reservoir. As a result, the frequency of administration can be reduced, also favoring the patient’s adhesion to therapy. In the main section of this review, we discuss some of the most common treatment options for ocular diseases, with a special focus on posterior segment treatments, and summarize the most recent improvement deriving from thermosensitive drug delivery strategies. Aside from this, an additional section describes the most widespread in vitro models employed to evaluate the functionality of novel ophthalmic drug delivery systems.

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.

Chitosan is an excipient which has been studied thoroughly in research works thanks to its positive characteristics such as muco-adhesiveness and ability to open epithelial-tight-junctions. In this article, lipophilic stearoyl chitosan (ST-CS) was synthetized in order to anchor this polymer to lipid nanoparticles and prepare ST-CS-coated nanoparticles (ST-CS-NP) using the microemulsion cold dilution technique. Curcumin (CURC) was used as model drug. CURC-ST-CS-NP were characterized by dimensional analysis, zeta potential, drug entrapment, drug release; tested in vitro on Human Umbilical Vein Endothelial Cell (HUVEC) cells to study its cytotoxicity and on human pancreatic cancer cells (PANC-1) to determine inhibition ability; tested in rats to determine CURC blood profiles and biodistribution. CURC-ST-CS-NP had mean diameters in the range 200–400 nm and CURC entrapment up to 73%. These systems did not show cytotoxicity on HUVEC cells at all tested dilutions and revealed to be more effective than free CURC solution on PANC-1 cells at 5 and 10 µM CURC. Blood profile studies evidenced as CURC entrapment in NP prolonged the permanence of drug in the systemic circulation compared to CURC solution due to a certain stealth property of NP, probably attributable to hydrophilic chitosan coating. Biodistribution studies showed a smaller CURC concentration in RES organs when CURC-ST-CS-NP were administered.