Skin drug delivery using lipid vesicles: A starting guideline for their development.

Lipid vesicles can provide a cost-effective enhancement of skin drug absorption when vesicle production process is optimised. It is an important challenge to design the ideal vesicle, since their properties and features are related, as changes in one affect the others. Here, we review the main components, preparation and characterization methods commonly used, and the key properties that lead to highly efficient vesicles for transdermal drug delivery purposes.

Exploration of Microneedle-assisted skin delivery of cyanocobalamin formulated in ultraflexible lipid vesicles.

Vitamin B12 (cyanocobalamin) deficiency is a widespread condition because of its different aetiologies, like malabsorption syndrome or lifestyles as strict veganism that is increasing its incidence and prevalence in developed countries. It has important haematological consequences that require pharmacological treatment. Current therapy consists of oral or parenteral supplements of cyanocobalamin; however, the oral route is discarded for malabsorption syndrome patients and the parenteral route is not well accepted generally.

Cyanocobalamin Ultraflexible Lipid Vesicles: Characterization and In Vitro Evaluation of Drug-Skin Depth Profiles.

Atopic dermatitis (AD) and psoriasis are the most common chronic inflammatory skin disorders, which importantly affect the quality of life of patients who suffer them. Among other causes, nitric oxide has been reported as part of the triggering factors in the pathogenesis of both conditions. Cyanocobalamin (vitamin B) has shown efficacy as a nitric oxide scavenger and some clinical trials have given positive outcomes in its use for treating skin pathologies.

Ciprofloxacin self-dissolvable Soluplus based polymeric films: a novel proposal to improve the management of eye infections.

Infections of the eye are among the leading causes of vision impairment and vision loss worldwide. The ability of a drug to access the anterior parts of the eye is negligible after systemic administration. Effective drug delivery to the eye is a major challenge due to the presence of protective mechanisms and physiological barriers that result in low ocular availability after topical application.

Microneedle-Based Delivery: An Overview of Current Applications and Trends.

Microneedle arrays (MNA) are considered as one of the most promising resources to achieve systemic effects by transdermal delivery of drugs. They are designed as a minimally invasive, painless system which can bypass the , overcoming the potential drawbacks of subcutaneous injections and other transdermal delivery systems such as chemical enhancers, nano and microparticles, or physical treatments. As a trendy field in pharmaceutical and biomedical research, its applications are constantly evolving, even though they are based on very well-established techniques.

Cubic Microcontainers Improve In Situ Colonic Mucoadhesion and Absorption of Amoxicillin in Rats.

An increased interest in colonic drug delivery has led to a higher focus on the design of delivery devices targeting this part of the gastrointestinal tract. Microcontainers have previously facilitated an increase in oral bioavailability of drugs. The surface texture and shape of microcontainers have proven to influence the mucoadhesion ex vivo.

Ultraflexible lipid vesicles allow topical absorption of cyclosporin A.

Psoriasis and atopic dermatitis are widespread pathologies with a need to improve their treatment. Topical administration of cyclosporine A (CyA) could be used if targeted to the skin, thus avoiding systemic levels. Unfortunately, CyA molecular weight and lipophilicity prevent its diffusion through human skin.

Effect of freezing and storage temperature on stability and antimicrobial activity of an antibiotic mixture used for decontamination of tissue allografts.

One of the most important risks to be controlled in tissue banking is the infection associated with the clinical use of auto- and allografts. Thus, tissue disinfection protocols are used, in addition to processing in controlled environments. For this purpose, combinations of antibiotics are designed to ensure a broad spectrum of antimicrobial activity.

Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2.

Purpose: The effective rat intestinal permeability (P ) was deconvolved using a biophysical model based on parameterized paracellular, aqueous boundary layer, transcellular permeabilities, and the villus-fold surface area expansion factor.

Methods: Four types of rat intestinal perfusion data were considered: single-pass intestinal perfusion (SPIP) in the jejunum (n = 40), and colon (n = 15), closed-loop (Doluisio type) in the small intestine (n = 78), and colon (n = 74). Moreover, in vitro Caco-2 permeability values were used to predict rat in vivo values in the rat data studied.

Targeted delivery of Cyclosporine A by polymeric nanocarriers improves the therapy of inflammatory bowel disease in a relevant mouse model.

The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects.

Polymeric microcontainers improve oral bioavailability of furosemide.

Microcontainers with an inner diameter of 223 μm are fabricated using the polymer SU-8, and evaluated in vitro, in situ and in vivo for their application as an advanced oral drug delivery system for the poorly water soluble drug furosemide. An amorphous sodium salt of furosemide (ASSF) is filled into the microcontainers followed by applying a lid using Eudragit L100. It is possible to control the drug release in vitro, and in vitro absorption studies show that the microcontainers are not a hindrance for absorption of ASSF.

Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands.

Telomeres and telomerase are key players in tumorogenesis. Among the various strategies proposed for telomerase inhibition or telomere uncapping, the stabilization of telomeric G-quadruplex (G4) structures is a very promising one. Additionally, G4 stabilizing ligands also act over tumors mediated by the alternative elongation of telomeres.

Stability of a Parenteral Formulation of Betamethasone and Levobupivacaine.

The therapeutic management of syndromes presenting simultaneously pain and inflammation often requires the administration of anesthetic and corticosteroid drugs by epidural administration. In this article, we studied a mixture that combines betamethasone and levobupivacaine, which demonstrates prolonged analgesic effects. To our knowledge, the stability of such a mixture in epidural solution has not been examined.

Provisional classification and in silico study of biopharmaceutical system based on caco-2 cell permeability and dose number.

Today, early characterization of drug properties by the Biopharmaceutics Classification System (BCS) has attracted significant attention in pharmaceutical discovery and development. In this direction, the present report provides a systematic study of the development of a BCS-based provisional classification (PBC) for a set of 322 oral drugs. This classification, based on the revised aqueous solubility and the apparent permeability across Caco-2 cell monolayers, displays a high correlation (overall 76%) with the provisional BCS classification published by World Health Organization (WHO).

Skin-PAMPA: a new method for fast prediction of skin penetration.

The goal of this study was to develop a quick, reliable, and cost-effective permeability model for predicting transdermal penetration of compounds. The Parallel Artificial Membrane Permeability Assay (PAMPA) was chosen for this purpose, as it already has been successfully used for estimating passive gastrointestinal absorption and blood-brain barrier permeability. To match the permeability of the rate-limiting barrier in human skin, synthetic certramides, which are analogs of the ceramides present in the stratum corneum, were selected for the skin-PAMPA model.

In Silico Prediction of Caco-2 Cell Permeability by a Classification QSAR Approach.

In the present study, 21 validated QSAR models that discriminate compounds with high Caco-2 permeability (Papp ≥8×10(-6)  cm/s) from those with moderate-poor permeability (Papp <8×10(-6)  cm/s) were developed on a novel large dataset of 674 compounds. 20 DRAGON descriptor families were used. The global accuracies of obtained models were ranking between 78-82 %.

Quantification of nortriptyline in plasma by HPLC and fluorescence detection.

A simple, sensitive and specific high-performance liquid chromatography method has been developed for the determination of nortriptyline (NT) in plasma samples. The assay involved derivatization with 9H-fluoren-9-ylmethyl chloroformate (Fmoc-Cl) and isocratic reversed-phase (C(18)) chromatography with fluorescence detection. The developed method required only 100 microl of plasma sample, deproteinized and derivatized in one step.

Wistar rat skin as surrogate for human skin in nortriptyline hydrochloride patch studies.

Six different matrices were prepared containing nortriptyline hydrochloride (NTH) with hydroxypropyl-methyl-cellulose as polymer. A mixture of transdermal enhancers was included as part of the vehicle. Diffusion studies were carried out through Wistar rat full thickness skin using Franz cells.

In situ kinetic modelling of intestinal efflux in rats: functional characterization of segmental differences and correlation with in vitro results.

The objective was to devise and apply a novel modelling approach to combine segmental in situ rat perfusion data and in vitro cell culture data, in order to elucidate the contribution of efflux in drug absorption kinetics. The fluoroquinolone CNV97100 was used as a model P-gp substrate. In situ intestinal perfusion was performed in rat duodenum, jejunum, ileum and colon to measure the influence of P-gp expression on efflux.

PAMPA--a drug absorption in vitro model 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones.

Parallel artificial membrane permeability assay (PAMPA) was used to measure the effective permeability, P(e), as a function of pH from 4 to 10, of 17 fluoroquinolones, including three congeneric series with systematically varied alkyl chain length at the 4'N-position of the piperazine residue. The permeability values spanned over three orders of magnitude. The intrinsic permeability, P(o), and the membrane permeability, P(m), were determined from the pH dependence of the effective permeability.

Activity-bioavailability balance in oral drug development for a selected group of 6-fluoroquinolones.

A nomogram is proposed to select the best candidate in drug development studies with quinolones and is intended to substitute other possible models. The nomogram is referred to as an activity-bioavailability balance (ABB) because it includes the following two criteria: ABB = [(1/gm MIC drug candidate)/ (1/gm MIC ciprofloxacin)].[(F(calc) drug candidate)/( F(calc) ciproflaxacin)].