Catarina Rosado

Bacterial cellulose membranes applied in topical and transdermal delivery of lidocaine hydrochloride and ibuprofen: In vitro diffusion studies

Bacterial cellulose (BC) is a biomaterial with unique physical and mechanical properties that triggered considerable interest, but there are few studies addressing the use of such membranes for drug loading and controlled release. This study aimed to investigate the applicability of BC membranes in topical or transdermal drug delivery systems. To assess its therapeutic feasibility, the permeation through human epidermis of two model drugs (lidocaine hydrochloride and ibuprofen) in BC and other formulation systems was compared in vitro. A uniform distribution of both drugs in the BC membranes was achieved. Diffusion studies with Franz cells showed that the incorporation of lidocaine hydrochloride in BC membranes provided lower permeation rates than those obtained with the conventional formulations. However, the results obtained with the lipophilic drug were quite different, since permeation of ibuprofen in BC was almost three times higher than that of the drug in the gel or in a PEG400 solution. These results indicate that this technology can be successfully applied to modulate the bioavailability of drugs for percutaneous administration, which could be particularly advantageous in the design of delivery systems that have, simultaneously, the ability to absorb exudates and to adhere to irregular skin surfaces.

Biocellulose membranes as supports for dermal release of lidocaine.

Biocellulose (BC) is a highly pure form of cellulose, produced in the form of a swollen membrane, with several applications in the biomedical area. In this study, the behavior of BC membranes as systems for topical delivery of lidocaine was evaluated. The BC-lidocaine membranes were prepared and characterized in terms of structural and morphological properties. A uniform distribution of the drug inside the BC membranes was observed. In vitro diffusion studies with Franz cells were conducted using human epidermal membranes and showed that the permeation rate of the drug in BC membranes was slightly slower than that obtained with the conventional systems, which was attributed to the establishment of interactions between the lidocaine molecules and the BC membrane, as evidenced by FTIR and NMR analysis. These results indicate that this methodology can be successfully applied for the dermal administration of lidocaine regarding the release profile and ease of application.

Effect of vehicle pretreatment on the flux, retention, and diffusion of topically applied penetrants in vitro.

AbstractPurpose. The flux of a topically applied drug depends on the activity in the skin and the interaction between the vehicle and skin. Permeation of vehicle into the skin can alter the activity of drug and the properties of the skin barrier. The aim of this in vitro study was to separate and quantify these effects. Methods. The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam) with log Koct/water values from 1.4 to 4.3 was measured over 4 h through heat-separated human epidermis pretreated for 30 min with vehicles having Hildebrand solubility parameters from 7.9 to 23.4 (cal/cm3)1/2. Results. Enhancement was greatest after pretreatment with the more lipophilic vehicles. A synergistic enhancement was observed using binary mixtures. The flux of diazepam was not enhanced to the same extent as the other permeants, possibly because its partitioning into the epidermis is close to optimal (log Koct 2.96). Conclusion. An analysis of the permeant remaining in the epidermis revealed that the enhancement can be the result of either increased partitioning of permeant into the epidermis or an increasing diffusivity of permeants through the epidermis.

Is there any barrier impairment in sensitive skin?: a quantitative analysis of sensitive skin by mathematical modeling of transepidermal water loss desorption curves

Background/purpose: Sensitive skin is a vague, subjective and difficult to characterize affliction. It affects a large part of the population and is accompanied with great interest by the cosmetic industry. Some studies have suggested that sensitive skin is the result of impaired barrier function, which leads to the exposure of immune system cells and sensitive nerves, resulting in marked cutaneous responses to otherwise harmless stimuli. This study aimed to investigate the cutaneous barrier integrity of individuals with sensitive skin by a novel approach: a plastic occlusion stress test followed by measurement of transepidermal water loss (TEWL) desorption curves.

Bacterial cellulose membranes as transdermal delivery systems for diclofenac: In vitro dissolution and permeation studies

Bacterial cellulose (BC) membranes were explored as novel nanostructured transdermal delivery systems for diclofenac sodium salt (a typical non-steroidal anti-inflammatory drug). Diclofenac sodium salt loaded BC membranes were prepared through a simple methodology, using glycerol as plasticizer, and characterized in terms of structure, morphology and swelling behavior. The membranes were very homogeneous, quite flexible and presented a considerably higher swelling behavior when compared with pure BC. In vitro diffusion studies with Franz cells, were conducted using human epidermal membranes, and showed that the incorporation of diclofenac in BC membranes provided similar permeation rates to those obtained with commercial patches and substantially lower than those observed with a commercial gel. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes clearly indicates the enormous potentialities of using BC membranes for transdermal administration of diclofenac.

Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters

The encapsulation of natural ingredients, such as rutin, can offer improvements in sun protection effectiveness. This strategy can provide enhanced flavonoid content and produces an improved bioactive compound with new physical and functional characteristics. As an alternative to common synthetic-based sunscreens, rutin-entrapped gelatin nanoparticles (GNPs) were designed and associated with ethylhexyl dimethyl PABA (EHDP), ethylhexyl methoxycinnamate (EHMC) and methoxydibenzoylmethane (BMDBM) in sunscreen formulations. The purpose of this study was to develop rutin-loaded gelatin nanoparticles and characterize their physicochemical, thermal, functional and safety properties. Rutin-loaded gelatin nanoparticles increased antioxidant activity by 74% relative to free-rutin (FR) solution. Also, this new ingredient upgraded the Sun Protection Factor (SPF) by 48%, indicating its potential as a raw material for bioactive sunscreens. The safety profile indicated that GNPs and glutaraldehyde (GTA) decreased HaCaT cell viability in a concentration/time-dependent manner. However, both blank nanoparticles (B-NC) and rutin-loaded nanoparticles (R-NC) had good performance on skin compatibility tests. These results functionally characterized rutin-loaded nanoparticles as a safe SPF enhancer in sunscreens, especially in association with UV filters.

Modeling TEWL-desorption curves: a new practical approach for the quantitative in vivo assessment of skin barrier

Abstract:  The objective of the present study was to test the discriminative capacity of the mathematical modeling of the transepidermal water loss (TEWL) curves that result from a plastic occlusion stress test (POST) to variations in the skin barrier – insults inflicted to the skin or differences in two distinct anatomical regions. This study was exclusively performed in the arm. On the first part of the work, three different insults to the skin barrier were assessed: tape stripping, lipid extraction with ether : acetone, and skin‐surface biopsy. Anatomical differences were studied in the mid‐forearm and in the wrist. All sites were submitted to a POST, after which the desorption curves were recorded. The mathematical model was adjusted to the TEWL data points. Results indicate differences in the parameters obtained in the control and treated sites, which suggests differences in the water dynamics after the damage was inflicted and shows that the method is valid for the objectives proposed. There were also significant differences in the parameters obtained in the wrist and in the volar forearm, which indicates that the method is also sensitive to variations in skin histology and anatomy.

Topical caffeine delivery using biocellulose membranes: a potential innovative system for cellulite treatment

Abstract In this study, biocellulose (BC) membranes have been investigated as caffeine topical delivery systems, for the potential treatment of cellulite. BC-caffeine membranes were prepared by a simple approach and the permeation of caffeine through human epidermis, from BC or from conventional formulation systems (solution and gel), was compared in vitro to assess their therapeutic applicability. Diffusion studies with Franz cells showed that the incorporation of caffeine in BC membranes provided lower permeation rates than those obtained with the conventional formulations. These results combined with the possibility of producing BC membranes with different shapes demonstrate that these materials are promising biosystems for topical delivery of caffeine, showing reproducibility and an extended and predictable caffeine release over time, leading to their potential use for cellulite attenuation.

Hydrocortisone-loaded poly(ε-caprolactone) nanoparticles for atopic dermatitis treatment.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects mostly young infants. The purpose of this research was to achieve a prolonged drug release and the reduction of side effects with hydrocortisone-loaded nanoparticles (NPs), for AD treatment. Poly(ε-caprolactone) (PCL) NPs were prepared by modified solvent displacement method and were characterized in terms of size, potential zeta, morphology, entrapment efficiency (EE), Fourier transform infrared (FT-IR) spectrometry and in vitro permeation studies using Franz cells. Toxicology of this nanosystem was also assessed. The obtained NPs EE showed an increased size and a more homogenous size distribution after loading and were negatively charged. EF was around 62%. In vitro release studies demonstrated a controlled release of drug from the NPs over time. FT-IR analysis showed the system stability for one week. Permeation studies revealed significant differences in the permeation of encapsulated and free hydrocortisone. In vitro toxicity studies showed no effect of drug toxicity after encapsulation. The study seems to indicate that encapsulation of hydrocortisone in PCL NPs could enable a faster control of the disease and a decrease in the side effects associated to the long-term application of corticosteroids.

Comparative assessment of the performance of two generations of Tewameter: TM210 and TM300.

The measurement of transepidermal water loss (TEWL) has been established as one of the main parameters in the assessment of skin barrier function. One of the most widely employed devices to measure TEWL is the Tewameter®. Courage and Khazaka launched the TM300 in 2003 and successfully eliminated some of the limitations of the previous model. In the more recent device, the sensors inside the probe head can be pre‐heated to a temperature close to that of the skin, which considerably decreases sampling time. Additionally, the new technology of the probe does not require frequent and time‐consuming recalibration with different solutions. The main objective of this work was to perform a comparative assessment of the performance of the two different Tewameter® models. Fifteen volunteers were used in this study, which was conducted in the mid‐portion of the volar forearm. The standard measurements assessed differences in the basal values, time necessary for a stable value and coefficient of variability under normal and extreme conditions. The dynamic measurements performed were based on a plastic occlusion stress test (POST), involving the application of an occlusive patch for 24 h, after which the TEWL desorption curves were recorded. A mathematical model was adjusted to the data points using a specially modified simplex routine. Calculated parameters considered relevant to the study were t1/2evap (evaporation half‐life) and dynamic water mass (DWM). Results show slight differences in the performance the two models, which are nevertheless statistically significant. The TM300 seems to be more sensitive to differences in TEWL and presents a much quicker measurement capacity. These results confirm a marked improvement in the more recent Tewameter® model, when compared with its predecessor. The main conclusion of this work is that caution is advised when comparing results obtained with the two different models and that studies should be carried out entirely with the same device.