New iron(III) anti-cancer aminobisphenolate/phenanthroline complexes: Enhancing their therapeutic potential using nanoliposomes.

Malignant melanoma is an aggressive and deadly form of skin cancer and novel and improved therapeutic options are needed. A promising strategy involves the use of metallodrugs combined with liposomes for targeted delivery to cancer cells. In this work, a family of iron(III) complexes was synthesized bearing a trianionic aminobisphenolate ligand (L) and phenanthroline-type co-ligands (NN). Four ternary iron complexes of general formula [Fe(L)(NN)] were obtained: [Fe(L)(amphen)] (1), [Fe(L)(phen)] (2), [Fe(L)(Clphen)] (3), and [Fe(L)(Mephen)] (4), as well as a fifth complex [Fe(L)(NEt3)(H2O)] (5) without the bidentate co-ligand. All complexes were characterized by analytic and spectroscopic techniques and demonstrated to be stable in aqueous environment. Complexes 1 and 2 were able to bind DNA and presented high cytotoxic activity towards human cancer cells. Complex 1 (IronC) was selected for incorporation into different liposomal formulations, which were fully characterized and screened against murine melanoma cells. The IronC liposomal formulation with the highest incorporation efficiency (∼95%) and a low IC50 value (7.1 ± 0.7 µM) was selected for in vivo evaluation. In a syngeneic murine melanoma model the liposomal formulation of IronC yielded the highest impairment on tumour progression when compared with the control, temozolomide, and with the iron complex in free form.

Biobased Ionic Liquids as Multitalented Materials in Lipidic Drug Implants.

Lipidic implants are valuable controlled delivery systems that present good biocompatibility and are useful for long-lasting therapies. However, these promising systems can present inflexible drug release profiles that limit their performance. Thus, finding new materials to overcome this drawback is crucial. Herein, lipidic implants containing caffeine and poorly soluble salicylic acid and rutin were developed. The inclusion of Gelucire® 50/02, sucrose, and two biobased ionic liquids, [Cho][Phe] and [Cho][Glu], were evaluated as a mean to improve the performance of the systems. The formulation procedure, dye content distribution, drug content, drug release, water content, and lipidic erosion of the developed systems were assessed. AFM analysis of the implants containing ILs was also performed. The results demonstrated that neither Gelucire® 50/02 nor sucrose were suitable tools to improve the drug release profile. In contrast, the ILs proved to be promising materials for multiple reasons; not only did they facilitate the formulation and incorporation of the studied drugs into the implants, but they also allowed a more suitable release profile, with [Cho][Glu] allowing a higher drug release due to its ability to increase surface wrinkling. Hence, this study showcases ILs as multitalented materials in lipid-based drug implants.

A Newfangled Collagenase Inhibitor Topical Formulation Based on Ethosomes with Sambucus nigra L. Extract.

Sambucus nigra L. (S. nigra) is a shrub widespread in Europe and western Asia, traditionally used in medicine, that has become popular in recent years as a potential source of a wide range of interesting bioactive compounds. The aim of the present work was to develop a topical S. nigra extract formulation based on ethosomes and thus to support its health claims with scientific evidence. S. nigra extract was prepared by an ultrasound-assisted method and then included in ethosomes. The ethosomes were analyzed in terms of their size, stability over time, morphology, entrapment capacity (EC), extract release profile, stability over time and several biological activities. The prepared ethosomes were indicated to be well defined, presenting sizes around 600 nm. The extract entrapment capacity in ethosomes was 73.9 ± 24.8%, with an interesting slow extract release profile over 24 h. The extract-loaded ethosomes presented collagenase inhibition activity and a very good skin compatibility after human application. This study demonstrates the potential use of S. nigra extract incorporated in ethosomes as a potential cosmeceutical ingredient and on further studies should be performed to better understand the impact of S. nigra compounds on skin care over the time.

Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach.

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process-however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

Further Evidence of Possible Therapeutic Uses of Sambucus nigra L. Extracts by the Assessment of the In Vitro and In Vivo Anti-Inflammatory Properties of Its PLGA and PCL-Based Nanoformulations.

Sambucus nigra L. is widely used in traditional medicine with different applications. However, confirmative studies are strongly required. This study aimed to assess the biological activities of the S. nigra flower's extract encapsulated into two different types of nanoparticles for optimizing its properties and producing further evidence of its potential therapeutic uses. Different nanoparticles (poly(lactide-co-glycolide, PLGA) and poly-Ɛ-caprolactone (PCL), both with oleic acid, were prepared by emulsification/solvent diffusion and solvent-displacement methods, respectively. Oleic acid was used as a capping agent. After the nanoparticles' preparation, they were characterized and the biological activities were studied in terms of collagenase, in vitro and in vivo anti-inflammatory, and in vitro cell viability. Rutin and naringenin were found to be the major phenolic compounds in the studied extract. The encapsulation efficiency was higher than 76% and revealed to have an impact on the release of the extract, mainly for the PLGA. Moreover, biochemical and histopathological analyses confirmed that the extract-loaded PLGA-based nanoparticles displayed the highest anti-inflammatory activity. In addition to supporting the previously reported evidence of potential therapeutic uses of S. nigra, these results could draw the pharmaceutical industry's interest to the novelty of the nanoproducts.

Preliminary Assays towards Melanoma Cells Using Phototherapy with Gold-Based Nanomaterials.

Cancer like melanoma is a complex disease, for which standard therapies have significant adverse side effects that in most cases are ineffective and highly unspecific. Thus, a new paradigm has come with the need of achieving alternative (less invasive) and effective therapies. In this work, biocompatible gold nanoparticles (GNPs) coated with hyaluronic acid and oleic acid were prepared and characterized in terms of size, morphology and cytotoxicity in the presence of Saccharomyces cerevisiae, and two cell lines, the keratinocytes (healthy skin cells, HaCat) and the melanoma cells (B16F10). Results showed that these GNPs absorb within the near-infrared region (750-1400 nm), in the optical therapeutic window (from 650 to 1300 nm), in contrast to other commercial gold nanoparticles, which enables light to penetrate into deep skin layers. A laser emitting in this region was applied and its effect also analyzed. The coated GNPs showed a spherical morphology with a mean size of 297 nm without cytotoxic effects towards yeast and tested cell lines. Nevertheless, after laser irradiation, a reduction of 20% in B16F10 cell line viability was observed. In summary, this work appears to be a promising strategy for the treatment of non-metastatic melanoma or other superficial tumors.

Combination of hyaluronic acid and PLGA particles as hybrid systems for viscosupplementation in osteoarthritis.

Hyaluronic acid (HA) is commonly used through intra-articular administration for viscosupplementation in osteoarthritis and other disorders. HA is generally supplied as an injection commonly reported as painful, with strong limitations after treatment. In this study, an alternative delivery system was constructed based on HA hydrogel and poly(lactic-co-glycolic acid) (PLGA) particles with oleic acid. Development studies included the determination of particle toxicity, hemolytic activity, in vitro and in vivo anti-inflammatory activity using macrophages and a murine model, respectively. This study showed that empty PLGA particles presented a mean size of 373 nm, while particles containing HA and oleic acid showed a marked particle size increase. The HA association efficiency was of 73.6% and 86.2% for PLGA particles without and with oleic acid, respectively. The in vitro HA release from PLGA particles revealed a sustained profile. Particles showed a good in vitro cell compatibility and the risk of hemolysis was less <1%, ensuring their safety. The in vivo anti-inflammatory study showed a higher inhibition for HA-loaded PLGA particles when compared to HA solution (78% versus 60%) and they were not different from the positive control, clearly suggesting that this formulation may be a promising alternative to the current HA commercial dosage form.