Luciano N. Mengatto

Recent Advances in Chitosan Films for Controlled Release of Drugs

Chitosan is a versatile carrier for biologically active agent from a small molecule such as an antibiotic to macromolecules such as proteins and nucleic acids. In addition, drug delivery devices based on chitosan can be available in a variety of morphologies including films, fibers, nanoparticles and microspheres. Otherwise the inherent advantages of this polymer such as biocompatibility, tissue adhesions and hydrophilic nature, chitosan can be modified to accomplish a specific purpose, for example improves release kinetics. In this review, recent patents of chitosan-based film systems for drug delivery are presented and discussed. This review include matrix type systems, membrane coated systems and film forming solution. For each one of these systems, several examples of manufacture processes, bioactive agents to be delivered and specifics applications are considered. This work highlights the use of chitosan in the film technology for drug delivery, presenting examples of chitosan used in an unmodified state and examples of modifications of the polymer backbone.

In vitro evaluation of suspoemulsions for in situ-forming polymeric microspheres and controlled release of progesterone

Abstract One possibility to obtain a higher dose of drug in a lower formulation volume can be by using of saturated quantity of drug in one of the phases of an emulsion. These formulations are called suspoemulsions (S/O/W). When a hydrophobic polymer is added to the organic phase of suspoemulsions, these formulations can be used to entrap the drug inside microspheres after in situ precipitation of the polymer–drug–excipients mix. In this work, performance and stability of progesterone suspensions in triacetin as organic phase of suspoemulsions were evaluated. These formulations were compared with O/W emulsions. Mathematical models were used to study in vitro release profiles. The results confirmed that S/O/W systems could be an attractive alternative to O/W formulations for the entrapment of progesterone inside poly(d,l-lactide-co-glycolide) microspheres. Diffusive-based models fit the in vitro release of progesterone from in situ-formed microspheres. For longer release periods, a time-dependent diffusion coefficient was successfully estimated.

Use of Chitosan Membranes to Mimic Human Epidermis for the Development of an Estradiol Delivery System

Polymeric membranes with skin-mimetic permeability properties appear as attractive models for use in the development of transdermal drug delivery systems. These membranes can be placed in contact with the transdermal system and simulate the skin barrier. In the current work, statistical experimental design was implemented for preparation of the optimized chitosan membrane to mimic human epidermis. For this purpose, an optimization process based on response surface methodology was carried out in order to determine the best combination of independent factors for membrane preparation. The independent factors analyzed were concentration of chitosan, concentration of cross-linking agent, and cross-linking time. The optimized membrane successfully simulated the cumulative amount of estradiol released per unit time for human epidermis. In addition, the optimized membrane was evaluated for the development of an estradiol delivery system. This in vitro technology may offer an alternative methodology for the development of transdermal delivery systems.

Paclitaxel delivery system based on poly(lactide-co-glycolide) microparticles and chitosan thermo-sensitive gel for mammary adenocarcinoma treatment

To evaluate the combination of more than one release system in the same formulation as a useful strategy to achieve paclitaxel delivery in a more sustained and controlled manner.

Recyclable amitraz-ethylene vinyl acetate strips used for beehives treatment against Varroa destructor

In this work, a new recyclable ethylene-vinyl acetate (EVA)-based strip impregnated with amitraz (AMZ) was prepared, characterized, and evaluated for the treatment of Apis mellifera against Varroa destructor. Bees are important for natural pollination, honey, and related goods production. Varroa destructor is currently considered one of the major pests and important efforts around the world are focused on methods for varroasis treatment. The procedure of strips preparation presented in this work consisted of two steps: impregnation and molding of impregnated pellets. Differential scanning calorimetry and gas chromatography–mass spectrometry analyses confirmed that AMZ molecule resisted the impregnation and molding conditions. The strips were sufficiently strong to resist destruction by the bees. The final infestation was lower in the hives treated with AMZ/EVA strips than in those treated with commercial strips. In order to check the possibility of recycling, strips were cut into little pieces and were subjected to total AMZ extraction. Finally, the fragments were exposed to re-impregnation and molding. The strips prepared after the recycling process presented the same shape and AMZ load than fresh strips.

Accurate prediction of shape and size of polyvinyl alcohol beads produced by extrusion dripping

Beads are one of the particulate delivery systems used to achieve protection and/or controlled delivery of different active ingredients or microorganisms. Polyvinyl alcohol is a non-toxic and biodegradable polymer and possesses extensive applications as a biomaterial. In the present work, two different strategies were applied for the prediction of shape and size of polyvinyl alcohol beads. These beads were obtained by extrusion dripping of a boric acid–polyvinyl alcohol aqueous solution into a basic aqueous gelling bath. The shapes and sizes of immature, mature and dry beads were determined using optical microscopy. Two different strategies included statistical and fluid dynamical (mechanistic) models to fit the experimental data. The shape of immature and mature beads was found to be dependent on the viscosity of the dripping solution for the former and the maturation time for the latter. The shape of dry beads was found to be mainly dependent on the particle contraction in the drying process. The size of mature and dried beads was correctly predicted from the operating conditions by means of a statistically developed model and from the dripping solution properties by means of a fluid dynamical approach. The optimal conditions for minimal dried bead size were calculated. The obtained mathematical models allow reduction in the amount of resources and time taken in the initial stages of the development of a novel encapsulated formulation. The mechanistic model may be applied to other polymeric systems once the corresponding parameters have been determined during proof-of-concept experiments.

Response surface method applied to optimization of estradiol permeation in chitosan membranes

The present work deals with the study of estradiol permeation in chitosan membranes. A fractional factorial design was built for the determination of the main factors affecting estradiol permeation. The independent factors analysed were: concentration of chitosan, concentration of cross-linking agent, cross-linking time and thermal treatment. It was found that concentration of chitosan and cross-linking time significantly affected the response. The effects of thermal treatment and concentration of cross-linking agent were not significant. An optimization process based on response surface methodology was carried out in order to develop a statistical model which describes the relationship between active independent variables and estradiol flux. This model can be used to find out a combination of factor levels during response optimization. Possible options for response optimization are to maximize, minimize or move towards a target value.