Innovative formulations for the ocular delivery of coenzyme Q10.

Coenzyme Q10 (CoQ10) is a lipophilic antioxidant agent that plays a crucial role in the mitochondrial electron transport chain. The neuroprotective role of CoQ10, countering mitochondrial dysfunction and oxidative stress, suggests its potential as an adjuvant for ocular neurodegenerative diseases linked to retinal cell loss. However, despite its promising properties, ocular barriers pose challenges for effective delivery.

Development, optimization and ex-vivo evaluation of a transdermal formulation containing trazodone.

Trazodone is a triazolpyridine derivative approved for the treatment of depression, and currently marketed as oral formulations. The transdermal administration of this drug could reduce side effects, related to peak plasma concentration, and improve patient adherence due to a reduced administration frequency. The aims of this work were: (a) the evaluation of the effect of pH vehicle and permeation enhancers on trazodone permeability across porcine skin ex-vivo; (b) the development and optimization of a transdermal drug delivery system containing trazodone hydrochloride.

A sterilizable platform based on crosslinked xanthan gum for controlled-release of polymeric micelles: Ocular application for the delivery of neuroprotective compounds to the posterior eye segment.

TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) polymeric micelles show interesting properties for ocular administration thanks to their solubilization capability, nanometric size and tissue penetration ability. However, micelles formulations are generally characterized by low viscosity, poor adhesion and very short retention time at the administration site. Therefore, the idea behind this work is the preparation and characterization of a crosslinked film based on xanthan gum that contains TPGS micelles and is capable of controlling their release.

Hyaluronic acid - PVA films for the simultaneous delivery of dexamethasone and levofloxacin to ocular tissues.

Ocular drug delivery is challenging due to the poor drug penetration across ocular barriers and short retention time of the formulation at the application site. Films, applied as inserts or implants, can be used to increase residence time while controlling drug release. In this work, hydrophilic films made of hyaluronic acid and two kinds of PVA were loaded with dexamethasone (included as hydroxypropylcyclodextrin complex) and levofloxacin.

Nanostructured Lipid Carriers for Enhanced Transscleral Delivery of Dexamethasone Acetate: Development, Ex Vivo Characterization and Multiphoton Microscopy Studies.

Corticosteroids, although highly effective for the treatment of both anterior and posterior ocular segment inflammation, still nowadays struggle for effective drug delivery due to their poor solubilization capabilities in water. This research work aims to develop nanostructured lipid carriers (NLC) intended for periocular administration of dexamethasone acetate to the posterior segment of the eye. Pre-formulation studies were initially performed to find solid and liquid lipid mixtures for dexamethasone acetate solubilization.

Buccal Permeation of Polysaccharide High Molecular Weight Compounds: Effect of Chemical Permeation Enhancers.

The greatest achievement in the advanced drug delivery field should be the optimization of non-invasive formulations for the delivery of high molecular weight compounds. Peptides, proteins, and other macromolecules can have poor membrane permeation, principally due to their large molecular weight. The aim of this work was to explore the possibility of administering fluorescently labeled dextrans (molecular weight 4-150 kDa) across the buccal mucosa.

An Alternative Device for the Topical Treatment of Oral Cancer: Development and Ex-Vivo Evaluation of Imiquimod-Loaded Polysaccharides Formulations.

The topical use of imiquimod (IMQ), a non-specific immune response modifier, showed to be a promising therapeutic option for the early-stage treatment of some type of oral cancer, even when performed with a formulation (Aldara®) developed and approved for skin application. The aim of this work was the development of buccal formulations for the topical administration of IMQ with improved mucosal retention and reduced trans-mucosal permeation when compared to the reference formulation. Three different hydrogels based on carboxymethyl chitosan (CMChit), sodium alginate (A), and xanthan gum (X) in different combinations were prepared, and the loading of imiquimod was successfully performed by using a micellar formulation based on d-α-tocopheril polyethylene glycol 100 succinate (TPGS).

Cyclosporine-loaded micelles for ocular delivery: Investigating the penetration mechanisms.

Cyclosporine is an immunomodulatory drug commonly used for the treatment of mild-to-severe dry eye syndrome as well as intermediate and posterior segment diseases as uveitis. The ocular administration is however hampered by its relatively high molecular weight and poor permeability across biological barriers. The aim of this work was to identify a micellar formulation with the ability to solubilize a considerable amount of cyclosporine and promote its transport across ocular barriers.

The Cultural Heritage of "Black Stones" (/) of Leopardi's Child Home (Recanati, Italy).

A macroscopic lithological study and physical (hardness, size, weight) investigations, coupled with laser-induced breakdown spectroscopy (LIBS) and X-ray fluorescence (XRF) chemical analyses of three egg- and one pear-shaped polished black stones, exposed in the library of the child home of the famous poet Giacomo Leopardi, at Recanati (Italy), were carried out. They are characterized by different sizes: two with the same weight of 16.9 kg and the two smaller ones of 5.

Development and validation of a HPLC-UV based method for the extraction and quantification of methotrexate in the skin.

An innovative and sensitive HPLC-UV method for the extraction and quantification of methotrexate (MTX) in skin layers was developed and validated. Owing to the physico-chemical characteristics of the drug and the nature of the tissue, it was necessary to use folic acid (FA) as an internal standard for MTX quantification in the dermis. MTX (and FA) analysis was performed on a Phenomenex Jupiter C column, using a 50 mm sodium acetate buffer (pH 3.

Improvement of Imiquimod Solubilization and Skin Retention via TPGS Micelles: Exploiting the Co-Solubilizing Effect of Oleic Acid.

Imiquimod (IMQ) is an immunostimulant drug approved for the topical treatment of actinic keratosis, external genital-perianal warts as well as superficial basal cell carcinoma that is used off-label for the treatment of different forms of skin cancers, including some malignant melanocytic proliferations such as lentigo maligna, atypical nevi and other in situ melanoma-related diseases. Imiquimod skin delivery has proven to be a real challenge due to its very low water-solubility and reduced skin penetration capacity. The aim of the work was to improve the drug solubility and skin retention using micelles of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of vitamin E, co-encapsulating various lipophilic compounds with the potential ability to improve imiquimod affinity for the micellar core, and thus its loading into the nanocarrier.

Preliminary Investigation on Simvastatin-Loaded Polymeric Micelles in View of the Treatment of the Back of the Eye.

There is increasing consensus in considering statins beneficial for age-related macular degeneration and in general, for immune and inflammatory mediated diseases affecting the posterior segment of the eye. However, all available data relate to oral administration, and safety and effectiveness of statins directly administered to the eye are not yet known, despite their ophthalmic administration could be beneficial. The aim was the development and the characterization of polymeric micelles based on TPGS or TPGS/poloxamer 407 to increase simvastatin solubility and stability and to enhance the delivery of the drug to the posterior segment of the eye via trans-scleral permeation.

Validation of a HPLC-UV method for the quantification of budesonide in skin layers.

A simple and sensitive HPLC method for the quantification of budesonide in skin layers was developed and validated. Budesonide was extracted from stratum corneum, epidermis and dermis by means of a mixture of acetonitrile:water (recovery > 90%). Budesonide quantification was performed with a RP-C18 column using methanol and water mixture (69:31, v/v) as mobile phase, pumped at 0.

Synthesis and Ex Vivo Trans-Corneal Permeation of Penetratin Analogues as Ophthalmic Carriers: Preliminary Results.

Among enhancing strategies proposed in ocular drug delivery, a rising interest is directed to cell penetrating peptides (CPPs), amino acid short sequences primarily known for their intrinsic ability to cell internalization and, by extension, to cross biological barriers. In fact, CPPs may be considered as carrier for delivering therapeutic agents across biological membranes, including ocular tissues. Several CPPs have been proposed in ophthalmic delivery, and, among them, penetratin (PNT), a 16-amino acids natural peptide, stands out.

In Vitro Skin Retention of Crisaborole after Topical Application.

Crisaborole, a nonsteroidal phosphodiesterase 4 inhibitor, represents the first nonsteroidal medication approved for the treatment of atopic dermatitis in over a decade. In this work, crisaborole skin permeation and retention was studied in vitro from a 2% ointment using porcine skin as barrier. Crisaborole was also characterized in terms of thermal behavior, solubility, and logP.

Ex Vivo Conjunctival Retention and Transconjunctival Transport of Poorly Soluble Drugs Using Polymeric Micelles.

This paper addresses the problem of ocular delivery of lipophilic drugs. The aim of the paper is the evaluation of polymeric micelles, prepared using TPGS (d-α-Tocopheryl polyethylene glycol 1000 succinate), a water-soluble derivative of Vitamin E and/or poloxamer 407, as a vehicle for the ocular delivery of dexamethasone, cyclosporine, and econazole nitrate. The research steps were: (1) characterize polymeric micelles by dynamic light scattering (DLS) and X-ray scattering; (2) evaluate the solubility increase of the three drugs; (3) measure the in vitro transport and conjunctiva retention, in comparison to conventional vehicles; (4) investigate the mechanisms of enhancement, by studying drug release from the micelles and transconjunctival permeation of TPGS; and (5) study the effect of micelles application on the histology of conjunctiva.

Development and validation of a simple method for the extraction and quantification of crisaborole in skin layers.

Crisaborole is a boron compound recently approved by the US Food and Drug Administration as a 2% ointment for the treatment of mild to moderate atopic dermatitis. This work describes a simple method for the quantification of the drug in the skin layers at the end of in-vitro permeation experiments. Chromatographic separation was carried out on a reverse-phase C column using a mixture of trifluoroacetic acid 0.

Ucuùba () Fat-Based Nanostructured Lipid Carriers for Nail Drug Delivery of Ketoconazole: Development and Optimization Using Box-Behnken Design.

Ucuùba fat is fat obtained from a plant found in South America, mainly in Amazonian Brazil. Due to its biocompatibility and bioactivity, Ucuùba fat was used for the production of ketoconazole-loaded nanostructured lipid carriers (NLC) in view of an application for the treatment of onychomycosis and other persistent fungal infections. The development and optimization of Ucuùba fat-based NLC were performed using a Box-Behnken design of experiments.

The role of vehicle metamorphosis on triamcinolone acetonide delivery to the skin from microemulsions.

After application to the skin surface, a topical formulation is submitted to changes in composition produced by evaporation of volatile components, penetration of components into the skin and extraction of skin components ("vehicle metamorphosis"). The aim of this work was to study the effect of vehicle metamorphosis on skin delivery from microemulsions containing triamcinolone acetonide. The microemulsions were prepared and characterized for water evaporation kinetics, in vitro release and skin permeation and retention.

Topical application of polymeric nanomicelles in ophthalmology: a review on research efforts for the noninvasive delivery of ocular therapeutics.

Introduction: Polymeric micelles represent nowadays an interesting formulative approach for ocular drug delivery, as they act as solubility enhancers of poorly soluble drugs and promote drug transport across cornea and sclera. In particular, in the last 5 years polymeric nanomicelles have been increasingly investigated to overcome some of the important challenges of the topical treatment of ocular diseases.

Areas Covered: The aim of this review was to gather up-to-date information on the different roles that polymeric micelles (commonly in the nanosize scale) can play in ocular delivery.

Thin polymeric films for the topical delivery of propranolol.

Background/aims: Infantile hemangioma (IH), the most common benign tumor of childhood, is currently treated with propranolol. The aim of this work was to study in vitro propranolol permeation and skin retention from an original polymeric film, composed of polyvinyl alcohol and an acrylic polymer.

Methods: Propranolol polymeric films were applied in occlusive and non-occlusive conditions, on either full thickness skin or isolated epidermis.

New Insights on the Mechanism of Fatty Acids as Buccal Permeation Enhancers.

Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect of a series of medium and long chain fatty acids on the permeation of a model high molecular weight and hydrophilic molecule, fluorescein isothiocyanate labelled dextran (FD-4, m.w.

Microemulsions based on TPGS and isostearic acid for imiquimod formulation and skin delivery.

Imiquimod (IMQ) is an immunostimulant drug topically used for the treatment of actinic keratosis and basal cell carcinoma. IMQ formulation and skin delivery is difficult because of its very low solubility in the most of pharmaceutical excipients and very poor skin penetration properties. The purpose of this study was to develop a microemulsion to optimize imiquimod skin delivery using d‑α‑tocopherol polyethylene glycol-1000 succinate (TPGS) as surfactant (so as to take advantage of its thickening properties) and isostearic acid as oil phase.

Cyclosporine-loaded cross-linked inserts of sodium hyaluronan and hydroxypropyl-β-cyclodextrin for ocular administration.

This work aimed to develop cyclosporine ocular inserts combining sodium hyaluronate (HA) and hydroxypropyl-β-cyclodextrin (HPβCD). Four different formulations, cross-linked with poly(ethylene glycol) diglycidyl ether, were studied to elucidate the role of the HA:HPβCD proportion on the physical characteristics and drug release patterns. The inserts (300 μm thickness) showed porous surfaces, high swelling ratios (∼10), and good cytocompatibility with fibroblasts and chorioallantoic membrane (HET-CAM test).

The Influence of Formulation and Excipients on Propranolol Skin Permeation and Retention.

The objective of this work was to study propranolol permeation and skin retention after topical application of different semisolid vehicles, with the final aim of developing new topical formulations intended for the treatment of infantile hemangioma, able to produce therapeutic drug levels in the skin, avoiding systemic absorption. Propranolol ointments, creams, and gels were prepared and tested on pig skin, an accepted model of human skin. From the results obtained in the present work it is clear that the permeation of propranolol across the skin is a poor predictor of its skin retention, at least in the time-frame considered.