Cutaneous permeation and penetration of sunscreens: formulation strategies and in vitro methods

Sunscreens are the most common products used for skin protection against the harmful effects of ultraviolet radiation. However, as frequent application is recommended, the use of large amount of sunscreens could reflect in possible systemic absorption and since these preparations are often applied on large skin areas, even low penetration rates can cause a significant amount of sunscreen to enter the body. An ideal sunscreen should have a high substantivity and should neither penetrate the viable epidermis, the dermis and the systemic circulation, nor in hair follicle. The research of methods to assess the degree of penetration of solar filters into the skin is nowadays even more important than in the past, due to the widespread use of nanomaterials and the new discoveries in cosmetic formulation technology. In the present paper, different in vitro studies, published in the last five years, have been reviewed, in order to focus the attention on the different methodological approaches employed to effectively assess the skin permeation and retention of sunscreens

In vitro evaluation of some parameters involved in mucoadhesion of aqueous polymeric dispersions

Context: The mucoadhesive formulations are constantly developing due to their relevance in the drug delivery to various districts of the organism. Objective: The purpose of this study was to find a direct link between physicochemical properties of the polymers and their adhesive ability in order to offer guidelines for the development of mucoadhesive semisolid formulations. Materials and methods: Twelve polymers were dispersed in water and characterized with regard to their mucoadhesiveness, apparent viscosity, contact angle on solid surface, and hydrodynamic diameter of their molecules. The adhesive properties were related to the other measured parameters. Results and discussion: The data seem to indicate the existence of an optimal value of viscosity, around 5–6 Pa s, to obtain the highest mucoadhesiveness of the polymeric dispersions. Regarding the molecular sizes, the best mucoadhesive performances seem to be given from polymers with a hydrodynamic diameter lower than 350–400 nm. In any case, the ability to wet the surface by the polymeric dispersion seems to play an essential role in bioadhesion process, capable of strongly limiting the phenomenon. Conclusions: Performing simple in vitro measurements, it seems possible to identify the best polymeric concentration to obtain a semisolid formulation with good mucoadhesive properties

Liposomes as a potential ocular delivery system of distamycin A

Liposomes containing Distamycin A (DA) may be clinically useful in the treatment of ocular HSV infections, especially in acyclovir-resistant HSV keratitis. This study evaluated the in vitro and in vivo performance of a topical controlled release liposomal formulation containing DA (DA-Lipo) aimed at reducing the toxicity of the encapsulated active agent and improving drug uptake by ocular tissues. The bioavailability of DA in the tear fluid and the DA uptake into the cornea were increased after instillation of DA-Lipo in rabbits, reaching the DA corneal concentration corresponding to IC50 values against HSV without any sign of transcorneal permeation of drug. DA-Lipo was definitely less cytotoxic then plain DA in rabbit corneal epithelial cells. These results provide new insights into the correlation between the in vitro data and the drug kinetics following ocular applications of liposomal vesicle

Ciclopirox Hydroxypropyl Chitosan (CPX‐HPCH) Nail Lacquer and Breathable Cosmetic Nail Polish: In Vitro Evaluation of Drug Transungual Permeation Following the Combined Application

Background: Onychomycosis produces nail chromatic alterations that lead patients to mask them with cosmetic enamels. Objectives: Evaluate drug transungual permeation and antimycotic activity against selected strains after application of CPX-HPCH nail lacquer (NL) on the nail pre-covered with breathable cosmetic polish. Methods: CPX transungual permeation after applying CPX-HPCH NL once or twice a day on bovine hoof membranes pre-covered with a breathable cosmetic nail polish was compared to that obtained applying CPX-HPCH NL directly on the membrane. The relevant experimental permeates underwent an in vitro susceptibility test. Results: After CPX-HPCH NL application once a day, the drug transungual flux in the presence of cosmetic product tended to decrease while maintaining the antifungal activity. Two daily applications of CPX-HPCH NL on the membrane pre-covered with cosmetic polish exhibited the same permeation profile as daily application of the medicated lacquer directly on the nail as well as the same microbiological activity. Conclusions: The breathable cosmetic nail polish can be applied on the nail affected by onychomycosis in association with CPX-HPCH NL to mask the imperfections. The application of CPX-HPCH NL twice a day appears to be a good solution to obtain the same results as for a daily application without the presence of the cosmetic laye

Reconstituted epithelial tissues and native cornea: A comparison of the influence of surfactants on ocular permeability

The aim of this study was to prepare an artificial rabbit corneal epithelium (RRCE) to compare with a human corneal epithelial model and excised rabbit cornea through permeation studies to investigate differences of surfactants influence on ocular permeability of a lipophilic compound. First solubility assays with different surfactants were performed and the integrity of the RRCE was assessed by measuring transepithelial electrical resistance (TEER). The permeation parameters showed that the RRCE was more sensitive than native cornea and human cornal epithelial model to the effect of permeation enhancers

Arabinogalactan as active compound in the management of corneal wounds: In vitro toxicity and in vivo investigations on rabbits

ABSTRACT: Purpose: Aims of the present investigation were to prove that natural polysaccharide arabinogalactan (AG) is well tolerated after ocular administration and exerts a high restoring effect on corneal epithelium abrasions. Materials and Methods: AG interactions with corneal cells, as well as its effect on their proliferation, were evaluated employing rabbit corneal epithelial cell cultures. The effects due to the presence of benzalkonium chloride (BAK) were also studied on cell cultures, ex vivo on rabbit isolated corneas, evaluating the hydration level, and on the healing rate of experimental corneal wounds in rabbits. Furthermore, the healing process of corneal lesions treated with an experimental 5.0% AG solution was studied and compared with those obtained applying solutions of hyaluronic acid and tamarind seed polysaccharide, both chosen as a reference by virtue of their well-known adjuvant properties on corneal trophism; the study was carried out by light and transmission electron microscopy. Results: BAK showed toxic effects on corneal epithelium in all experiments. AG proved to stimulate the growth of the corneal epithelial cells by interacting at the level of the cell plasma membrane. The microscopy observations of the epithelial surface of AG-treated damaged corneas revealed a well-restored and histologically organized ultrastructure characterized by fully formed microvilli and glycocalyx; the healing process resulted faster with respect to spontaneously recovered untreated corneas. Conclusion: Our results suggest that AG can interact with corneal epithelial cells without any toxic side effect; moreover, it proved to stimulate cell proliferation, thus promoting tissue re-epithelialization and reorganization just 48hr post-woundin

Polyvinyl alcohol/cellulose hydrogel as possible corneal stroma substitute in drug permeation tests

The permeation studies of active compounds and formulations are necessary to verify the capability of molecules to pass through the physiological barrier of our body. In order to develop a 3D model of the cornea, preparation and characterization of different hydrogels as corneal stroma substitutes were tested

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices

Albuterol prodrugs for ocular administration: Synthesis and evaluation of the physico-chemical and IOP-depressant properties of three albuterol triesters

Three albuterol (salbutamol) new triesters (acetyl, isobutyryl and pivalyl) were prepared and evaluated in vitro (rate of chemical hydrolysis at different pH values, relative lipophilicity) and in vivo (depression of intraocular pressure, IOP, in a rabbit model of ocular hypertension). The three esters underwent quantitative hydrolysis in vitro to give the parent compound: first-order kinetics were observed, for several half-lives, for the disappearance of the compounds from solution at different pH values. The degradation mechanism, presumably involving a sequence of hydrolytic steps, was not investigated in detail. The rate constants for disappearance of the triesters and for formation of albuterol were in the order acetyl > isobutyryl > pivalyl; the relative lipophilicities of the compounds, as estimated by the corresponding reversed phase HPLC 'capacity factors', were in the order albuterol < acetyl < isobutyryl < pivalyl. When tested for reduction of IOP, all three ester solutions proved significantly more active than albuterol at several times after administration. The tripivalyl ester, in particular, after 5 h appeared more active than the other two esters, and, together with the triisobutyryl ester, was significantly more active than the triacetate after 8 h. These findings confirm the.important influence of (pro)drug lipophilicity on transcorneal penetration. The in vivo tests also indicated that the ocular irritant properties of the parent drug were still present, albeit to a smaller degree, in the triester derivatives