Helena Marques

University of Lisbon | UL · Faculty of Pharmacy

Background Basal cell carcinoma (BCC), the most common malignant tumor, accounts for 85%–95% of cases of eyelid malignant tumors. Demographic factors such as age, gender, tumor location, and subtype play a crucial role in epidemiological knowledge. We investigated eyelid BCC diagnosis and treatment at the Department of Ophthalmology in Centro Hospi...

Background: Basal cell carcinoma (BCC) is the most common malignant eyelid tumour encountered by oculoplastic surgeons (ophthalmologists), contributing significantly to morbidity. The objective of this study was to assess awareness levels and knowledge among healthcare professionals and the general public, regarding eyelid BCC, with a specific focu...

Cyclodextrin (CD) drug delivery systems offer the potential to enhance the desired physicochemical properties and pharmacokinetic parameters of drugs while maintaining their safety. Cyclodextrin-glucosyl-transferase (CGTase) is amongst the most important enzymes used in CD biosynthesis. However, the bioproduction of CDs still faces challenges in te...

Multicomponent synthesis are convergent reactions in which three or more starting materials react in a single step to form the product. In the discovery and development of new drugs, multicomponent reactions offer several advantages over traditional synthesis: shorter experiment time, less need for laboratory techniques and scalability. Thus, the o...

The aim of this work was to prepare and characterize inclusion complexes between a synthetic curcumin analog (dibenzalacetone, DBA) and beta-cyclodextrin (β-CD); and to evaluate their in vitro antileishmanial activity. DBA was synthetized and characterized by spectroscopic methods and the inclusion complexes were obtained by kneading and lyophiliza...

We report the synthesis of water soluble cyclodextrin (CD) polymers prepared by crosslinking pyromellitic dianhydride (PMDA) with two CD derivatives (methyl-β-CD - MβCD and (2-hydroxy)propyl-β-CD - HPβCD) and their evaluation as functional sub-micron sized carriers in the development of antiretroviral drug delivery systems. Using the protease inhib...

The development of orodispersible tablets (ODTs) for poorly soluble and poorly flowable drugs via direct compression is still a challenge. This work aimed to develop ODTs of poorly soluble drugs by combining cyclodextrins that form inclusion complexes to improve wetting and release properties, and directly compressible co-processed excipients able...

This work aimed to explore the combination of hydrophilic and hydrophobic cyclodextrins to prepare bilayer tablets that can perform as quick/slow biphasic release systems of a poorly soluble drug. This formulation approach is of particular interest for treatments that require a rapid action followed by sustained therapeutic levels. Carbamazepine (C...

The objective of the present work was to characterize the ability of liposomes and cyclodextrin (CyD) complexes to modulate the in vivo profile of fluticasone (FTZ). In vitro cell compatibility tests were performed, exposing A549 cells to FTZ in the free form and FTZ associated to liposomes and complexed with CyD. The in vivo fate of a selected FTZ...

Lopinavir (LPV) is currently used in combination with ritonavir for the clinical management of HIV infections due to its limited oral bioavailability. Herein, we report the application of an in silico method to study cyclodextrin (CyD) host-guest molecular interaction with LPV for the rational selection of the best CyD for developing a CyD based LP...

The European Pharmacopoeia is a regional pharmacopoeia published by the European Directorate for the Quality of Medicines and HealthCare of the Council of Europe based in Strasbourg. This entity includes the European Pharmacopoeia Commission and coordinates the European Network of Official Medicines Control Laboratories. From 1964 to 2018, nine off...

This work aimed to explore for the first time the use of cyclodextrins to prepare printlets of poorly soluble drugs, such as carbamazepine, which require fine dose adjustment and rapid release. Orodispersible (flash) and immediate release formulations were 3D printed via semisolid extrusion of wet masses of hydroxypropyl-β-cyclodextrin (HPβCD) and...

Citrus fruits and juices are recognized as one of the most healthful components of the human diet. Limonin is a bitter compound, highly oxygenated triterpenoid, that occurs as aglycones in some citrus fruits. The aim of this work was to (i) complex limonin in cyclodextrins to reduce bitterness in orange juice and (ii) evaluate limonin anti-inflamma...

Cyclodextrins are cyclic carbohydrates widely used as complexing and non-complexing excipients in drug delivery systems. The purpose of this work was to study the ability of hydroxypropyl-β-cyclodextrin and β-cyclodextrin to act as tablet fillers for direct compression. In this way, several parameters of the cyclodextrins were evaluated, namely: (i...

This paper aims to provide a critical review of cyclodextrins as excipients in tablet formulations, highlighting: (i) the principal pharmaceutical applications of cyclodextrins; (ii) the most relevant technological aspects in pharmaceutical formulation development; and (iii) the actual regulatory status of cyclodextrins. Moreover, several illustrat...

Background: Cyclodextrins (CDs) are versatile excipients with an essential role in drug delivery, as they can form non-covalently bonded inclusion complexes (host-guest complexes) with several drugs either in solution or in the solid state. Methods: The main purpose of this publication was to carry out a state of the art of CDs as complexing age...

Herein we report the formation of dry powder complexes of ibuprofen (IBU) and hydroxypropyl-γ-cyclodextrin (HP-γ-CyD) by supercritical CO2-assisted spray-drying (SASD). SASD of HP-γ-CyD alone, IBU/HP-γ-CyD, as well as the physical mixture were prepared and characterized using attenuated total reflectance Fourier transform infrared spectroscopy (ATR...

Oral delivery of many therapeutic agents remains challenging due to gastric insolubility/poor dissolution, inefficient intestinal permeability and pre-systemic inactivation. These problems limit the advantages of convenience and increased compliance they provide in the therapy of many chronic diseases. Cyclodextrin nanosystems have emerged as promi...

A major part of asthma treatment is made by the use of preventive inhalation drugs. The Pressurized Metered-Dose Inhalator (pMDI) has been the backbone device for this treatment, due to its simplicity, portability and widely acceptance. But no device comes without its limitations, and pMDI is hard to handle properly by elders and children < 5 years...

Supplementary Material contains parallel and preliminary studies regarding lycopene vehiculation, effect of UV-B on cell metabolic activity and apoptosis by MTT and Annexin-V assays, respectively.

Lycopene has been reported as the antioxidant most quickly depleted in skin upon UV irradiation, and thus it might play a protective role. Our goal was to investigate the effects of preexposure to lycopene on UV-B-irradiated skin cells. Cells were exposed for 24 h to 10 M lycopene, and subsequently irradiated and left to recover for another 24 h pe...

Asthma treatment provided by a pressurized Metered Dose Inhaler (MDI) coupled to a Valved Holding Chamber (VHC), in cases of children younger than 5 years old, is a standard well-stablished in the medical community. The lack of experimental studies for comparison of several commercial VHC alternatives is the main goal of this study. The VHC device...

Cyclodextrins (CDs) were first isolated in 1891 as degradation products of starch from a medium of Bacillus amylobacter. They are cyclic water-soluble, nonreducing, macrocycle carbohydrate polymers constructed from (1-4)-linked d-glucopyranose units (naturally occurring, and formed by 6, 7, and 8 glucose units), in a ring formation and present a to...

The worldwide incidence of asthma yields 250,000 deaths annually, being almost all of these deaths avoidable. The inhalation therapy is the preferable route to deliver bronchodilator/anti-inflammatory drugs to the patient lungs. Within this route of treatment, pressurized Metered Dose Inhalers (pMDI’s) are the cornerstone devices. When coupled with...

Asthma treatment by inhalation in young children, or elderly people with poor coordination, is advisable to be made through a Valved Holding Chamber (VHC) device when a pressurized metered-dose inhaler is prescribed. An analysis of the emitted dose (ED) from VHC devices is of utmost importance to infer about the best market option for a certain pat...

Due to the increasing worldwide incidence of asthma, a growing usage of inhalation devices has been observed. Some of the pressurized Metered Dose Inhalers (pMDI) limitations have been overcome by the introduction of newly and improved Valved Holding Chambers (VHC), resulting in good patient acceptance. The efficiency is assessed by the VHC Emitted...

Cyclodextrins (CDs) were first isolated in 1891 as degradation products of starch from a medium of Bacillus amylobacter. They are cyclic water-soluble, nonreducing, macrocycle carbohydrate polymers constructed from α-(1-4)-linked d-glucopyranose units (naturally occurring α, β, and γ formed by 6, 7, and 8 glucose units), in a ring formation and pre...

Corticosteroids like ciclesonide are used to manage asthma. However, its physicochemical properties-namely water solubility-and, consequently, pharmacokinetics and pharmacodynamics could be object of improvement. One way to achieve this is by the use of cyclodextrins, a well-known group of molecules able to include water-insoluble molecules, solubi...

Unlabelled: BACKGROUND & SCOPE OF THE REVIEW: This review focuses on the UV radiation effects on skin, emphasizing the photoaging process, and the photoprotection conferred by tretinoin (all-trans retinoic acid or ATRA). Tretinoin is still the best tested retinoid to reverse photoaged skin. Major conclusions: Tretinoin can be used for photoaging...

The work herein reported presents the influence of dimensional wall design in the size of the recirculation area, developed in the expansion corner of a valved holding chamber device (VHC). Those are add-on medical devices used with the pressurized Metered Dose Inhaler (pMDI). The latest is the cornerstone in the inhalation therapy for asthma and o...

Background & Scope of the reviewThis review focuses on the photoprotection conferred by lycopene, one of the most potent antioxidants. Lycopene has been recently proposed to play a critical role on anticarcinogenic action at different levels.Major Conclusions The photoprotective properties of lycopene remain contradictory. Some studies point out a...

Introduction Ultradeformable vesicles are highly promising tools to enhance the percutaneous transport of different drugs such as tretinoin across the skin barrier and also to increase the formulation stability at absorption site and reduce the drug induced irritation. Methods Topical delivery of tretinoin-loaded ultradeformable vesicles (tretinoin...

Several ocular treatment options have been developed to overcome a broad range of ocular infections and corneal pathologies. Even though, commonly used ophthalmic formulations are only able to promote a short therapeutic effect, demanding a frequent dosing regimen. This study took advantage of dimethyl-b-cyclodextrin to overcome prednisolone low wa...

Fluticasone propionate is a highly potent corticosteroid used to treat asthma and allergic rhinitis. It is a very effective drug, but has the inconvenient factor of being insoluble in water. Cyclodextrins were used to improve this limitation because of their ability to form inclusion complexes with guest drug molecules as well as increase the stabi...

Corticosteroids (Cort) such as Budenoside, Fluticasone Propionate, Mometasone Fuorate are used as treatment for respiratory diseases due to high anti-inflammatory effect, but they present some limitation in terms of formulation, namely high lipophilicity. Usually, these drugs are administered through pulmonary route, requiring high doses to have a...

Lung diseases are more effectively treated with local therapy when compared to systemic delivery. Unique features such as surface area, permeability and blood supply, make the pulmonary route an attractive and non-invasive way for drug delivery. Standard therapy consists of β-adrenergic agonists and corticosteroids inhalers. Although effective, cor...

The aim of this study was to investigate the influence of different cyclodextrins (CyD) on physical characteristics of inhalation dry powders. The particle size was characterised by Aerosizer LD and aerodynamic behaviour of inhaled complexes assessed by twin-stage liquid impinger. The in vitro release profile of the powders was studied through Fran...

Background: The objective of this work is to numerically evaluate several commercial Valved Holding Chamber (VHC) geometries, in terms of airflow behavior and wall deposition. Also, the Fine Particle Dose (FPD) and Mass Mean Aerodynamic Diameter (MMAD) of the drug dose reaching the lungs were evaluated. Downwards the VHC Mouthpiece, the USP Throat...

Asthma is an inflammatory chronic disease characterized by airway obstructions disorders. The treatment is usually done by inhalation therapy, in which pressurized metered-dose inhalers (pMDIs) are preferred devices. The objective of this paper is to characterize and simulate a pMDI spray plume by introducing realistic factors through a computation...

Typically for young children and elders, the asthma treatment procedure using pMDI devices bring some usage coordination difficulties. Therefore, and accordingly to several asthma treatment guidelines, the prescription of a VHC, as an add-on device for the pMDI, is advisable. These devices consist of an expansion chamber where the air slows down, a...

Pulmonary administration of drugs is primarily suggested for “local” pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, but it can be also efficient for the treatment of systemic diseases [1]. The fast onset of action and the high surface region (80-100 m2) confers the lung attractive attributes as an organ for drug deliv...

Asthma is an inflammatory chronic disease characterized by airway obstructions disorders. The treatment is usually done by inhalation therapy, where pressurized metered-dose inhalers (pMDIs) are a preferred device. The objective of this paper is to characterize and simulate a pMDI spray plume by introducing realistic factors through a computational...

Purpose: The aims of this experimental work were the incorporation and full characterization of the system Tretinoin-in-dimethyl-beta-cyclodextrin-in-ultradeformable vesicles (Tretinoin-CyD-UDV) and Tretinoin-in-ultradeformable vesicles (Tretinoin-UDV). Methods: The Tretinoin-CyD complex was prepared by kneading and the UDV by adding soybean pho...

The present project analyses the streamlines patterns that influence the efficiency of the holding chambers (used in asthma treatment) and relate it with the geometric dimensions of the device. According to some unpublished observations, the utmost significant drug delivery faction for the treatment (the fine particle fraction below 6.0 µm in diame...

Several aspects are known to influence the drug distribution within the low respiratory tract, with particular emphasis on those related to the inhalation device. The aim of this work was to assess the performance of three spacers in the drug release, and also the quantity of active agent deposited inside these devices. In order to evaluate the beh...

The aim of this work was to study the release, permeation and skin retention profiles of 0.05% tretinoin hydrogel formulations in which tretinoin was in free form or complexed with dimethyl-beta-cyclodextrin in a stoichiometry of 1:4. Theoretically, this complexation will mainly allow to: overcome drug’s low water solubility and low stability; enha...

The objective of this work was to develop solid dosage forms using powders containing inclusion complexes (ibuprofen with β-cyclodextrin) which were used to produce tablets (direct compression without additional excipients) and pellets (extrusion/spheronization) from wet mass containing 40% (w/w) of microcrystalline cellulose. The pellets also demo...

Powders containing indometacin complexed with β-cyclodextrin (1:1 ratio) obtained by two complexation methods (suspension/solution [with water removed by air stream, spray– and freeze–drying] and kneading techniques) were compared between them to observe the increase on the drug solubility and yield of the complexation process. The tests used for t...

Introdução: Existem vários factores que afectam a distribuição do fármaco nas vias áreas inferiores, onde podemos destacar os factores associados ao próprio dispositivo de inalação. Este trabalho tem como objectivo avaliar o desempenho da libertação de fármaco em três câmaras de expansão, assim como a quantidade de agente activo depositada no seu i...

Reactive oxygen species (ROS) and free radicals have been implicated in a number of diseases and disorders, and the skin, for its localization, is exposed to a large number of environmental threats. Free radical scavengers and antioxidants have thus been proposed as protective or therapeutic agents against ROS-mediated injuries. Oral treatment with...

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability, and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects an...

Finasteride is a practically insoluble in water drug that belongs to the Class II of the BCS (poor solubility and high permeability). Solid dispersions are solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. Solid dispersions are a successful strategy to improve drug release of poor...

The aim of this work is to prepare tretinoin/dimethyl-beta-cyclodextrin complexes and fully characterize them through various analytical techniques. According to the phase solubility studies performed, the equilibrium for maximum complexation is reached in about 8 days presenting an AL-type diagram (soluble complexes) corresponding mainly to 1:1 st...

The aim of this work was to develop and characterize a 0.05% tretinoin hydrogel formulations in which tretinoin is free or complexed with dimethyl-beta-cyclodextrin in order to compare the main advantages of its complexation. Theoretically, the complexation will mainly allow to: overcome drug low solubility in water and low stability; enhance the d...

Cited By (since 1996):3, Export Date: 23 March 2014, Source: Scopus

Mixtures containing ibuprofen (IB) complexed with β-cyclodextrin (βCD) obtained by two complexation methods [suspension/solution (with water removed by air stream, spray- and freeze-drying) and kneading technique] were processed into pharmaceutical dosage forms (minitablets and capsules). Powders (IB, βCD and IBβCD) were characterized for moisture...

Cyclodextrins (CyDs) are cyclic carbohydrates derived from starch. The parent CyDs contain six, seven and eight glucopyranose units and are referred as -, β- and -CyD, respectively. The most important property of the CyDs is the ability to establish specific interactions – molecular encapsulation – with various types of molecules through the format...

Omeprazole (OME) exhibits low stability to light, heat and humidity. In stress conditions OME stability should improve under inclusion complex form with hydroxypropyl-β-cyclodextrin (HPβCD). Stability of OME, its physical mixture (PM) with HPβCD and OME:HPβCD inclusion complex was assessed during 60days. The inclusion complexes were prepared by kne...

Cyclodextrins are cyclic oligosaccharides of alpha-(1,4)-linked D-glucopyranose units in a ring formation. They are able to form inclusion complexes with a wide variety of molecules, improving their aqueous solubility and chemical stability, the dissolution and release rates of several molecules as well as suppressing their volatility and unpleasan...

This study aims to develop and characterise a beclomethasone diproprionate:gamma-cyclodextrin (BDP:gamma-CYD) complex and to optimise the variables on the spray-drying process, in order to obtain a powder with the most suitable characteristics for lung delivery. The spray-dried powder--in a mass ratio of 2:5 (BDP:gamma-CYD)--was physically mixed wi...

This paper is a general overview that contributes for the knowledge systematization concerning the characteristics of the acne in the adult, its prevalence, causes, diagnosis, classification and drugs available for treatment. The reference therapy is the combination between topical retinoids and oral antibiotics. Oral isotretinoin is still the only...

The work aims to prove the complexation of two model drugs (ibuprofen, IB and indomethacin, IN) by beta-cyclodextrin (betaCD), and the effect of water in such a process, and makes a comparison of their complexation yields. Two methods were considered: kneading of a binary mixture of the drug, betaCD, and inclusion of either IB or IN in aqueous solu...

The aim of the present study was to evaluate the performance of Ventilan® coupled to the Volumatic® spacer. An experimental study was conducted using the four stage Multistage Liquid Impinger (MSLI). This enabled the observation that half of the pharmacological dose is retained within the body of the spacer. Therefore, the air flow inside the space...

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(−)-α-bisabolol was found to form an inclusion complex with β-cyclodextrin (β-CD) in solution as well as in the solid state. To investigate molecular associations of β-CD with pure (−)-α-bisabolol or (−)-α-bisabolol as a component of camomile essential oil, phase solubility studies were undertaken. A Bs type solubility with an apparent complex cons...

Supercritical carbon dioxide (scCO2)offers several attractive scenarios for thepharmaceutical processing as an alternativeto aqueous and organic solvents. In thiswork naproxen, a widely used non steroidalanti-inflammatory drug with analgesic andanti-inflammatory properties, was chosenas a model drug. Its complexation with cyclodextrinsimproves the...

Naproxen is a poorly soluble anti-inflammatorydrug, the solubility of which canbe enhanced by complexation withbeta-cyclodextrin. Besides that, the inclusioncomplex reduces the incidence of gastrointestinal side effects of the drug. The aim of this work was to compare the physicochemical characteristics of the solid complexes prepared by traditiona...

The purpose of this study is to evaluate the effect of budesonide-cyclodextrins (CDs) complex formation in the in-vitro aerodynamic properties of the dry powder produced for pulmonary delivery. Phase-solubility studies were performed using budesonide and -CD, DM--CD and HP--CD. The complex budesonide:DM--CD revealed the highest stability consta...

Particle size analysis of drug and excipient is of particular interest for dry powder inhalation (DPI) formulations development and quality control. In this work, the deposition in the upper, the medium and the lower (i.e. the respirable fraction) Twin Impinger compartments of sodium cromoglycate (SCG), lactose (as excipient) and a 1:1 mixture ther...

Cyclodextrins (CDs) are molecules of natural and semi-synthetic origin, that turns them practically innocuous to humans when used externally or internally. In the last 10 years, this group of compounds has been having a great application in the Pharmaceutical and Food Industry, but only recently the Cosmetic Industry began to use CDs for molecular...

An isocratic liquid chromatographic method for the separation and simultaneous determination of retinyl acetate, propionate or palmitate (esters of vitamin A), beta-carotene (pro-vitamin A), ascorbic acid (vitamin C) and DL-alpha-tocopherol (vitamin E) is described. Samples are analysed by means of a reversed-phase column (LiChrospher 100 RP-18), u...

Cyclodextrins can be used in order to suitably modify the biopharmaceutical properties of drugs. A complex of beclomethasone dipropionate/hydroxypropyl-β-cyclodextrin was formed as shown by the apparent solubility constant, differential scanning calorimetry and X-ray spectroscopy. With a view to developing a suitable formulation for pulmonary deliv...

Dry Powder Inhalers (DPIs) are devices used for pulmonary administration of drugs. They have known an increasing importance, namely in asthma treatment, in substitution of MDIs due to the ban of CFC propellants, which destroy the ozone layer (1).

Among the many potential pharmaceutical applications of cyclodextrins, their ability to prolong a biological effect can be a useful characteristic. Sustained pulmonary release of drugs that require multiple administrations per day, such as salbutamol (a ß2-selective adrenoreceptor agonist used in Asthma therapy), would be advantageous.

This paper is the second of a series about cyclodextrins and reviews their application in various fields. It also includes a review of the literature on the mechanism and thermodynamics of complex formation.

This paper is the first of a series about cyclodextrins and reviews their structure, properties, complex formation and the determination of cyclodextrin-drug stability constants.

This paper is the fourth of a series about cyclodextrins (CYDs) and reviews the most commonly used of its derivatives. The absorption, fate and toxicity in body is also reviewed.

The fate of β-cyclodextrin (β-CYD) and some of its derivatives is reported following pulmonary administration in order to evaluate the feasibility of using β-CYDs for sustaining pulmonary drug action or for controlling systemic drug levels following pulmonary administration. Using a randomised cross-over design, the absorption and pharmacokinetics...

The present study details the fate of an HP-β-CYD-salbutamol complex following pulmonary administration in order to evaluate the possibility of obtaining sustained release of salbutamol using HP-β-CYD as a carrier. Using a randomised cross-over design, the absorption and pharmacokinetics of HP-β-CYD-salbutamol complex have been investigated in four...

Cyclodextrins (CYDs) are cyclic non-reducing oligosaccharides built up from six, seven or eight glucopyranose units (α-, β- or γ-CYD, respectively). Many drugs are able to form an inclusion complex with CYDs, being trapped entirely or at least partially into their slightly apolar cavities. Complexes of CYDs and salbutamol were obtained in both the...

β-Cyclodextrin (β-CYD) has a hydrophobic cavity in which salbutamol may be clathrated. The ability of a guest molecule to penetrate the CYD host is determined by its size, stereochemistry and polarity. Intermolecular interactions such as the hydrophobic interaction, van der Waals forces, H bonding and other physical forces are involved in the inclu...