Several diseases would benefit from prolonged drug release provided by systems retained in the stomach for extended time periods. Expandable gastroretentive devices are administered in a collapsed configuration enabling swallowing and regain in situ their native shape having larger spatial encumbrance, thus hindering voidance through the wide open pylorus. An expandable system for gastric retention was here proposed relying on the shape memory behavior of pharmaceutical-grade poly(vinyl alcohol). Different original configurations to be recovered upon exposure to aqueous fluids at 37 °C, potentially enabling gastric retention, were conceived. Prototypes containing allopurinol were directly manufactured by fused deposition modeling or shaped by purposely-designed templates from hot melt extruded rods immediately after production. Various temporary shapes, in principle suitable for administration, were programmed by manual deformation of samples by means of specific templates, under defined temperature conditions. In 0.1N hydrochloric solution at 37 °C, the prototypes recovered their original shape, reaching the desired spatial encumbrance within few minutes. Release from the samples, although of relatively short duration, was independent of the original shape and processing undergone, and was noticeably slowed down by application of Eudragit RS/RL-based coatings.
Retentive device for intravesical drug delivery based on water-induced shape memory response of poly(vinyl alcohol): design concept and 4D printing feasibility
The term “4D printing” refers to the development of stimulus‐responsive structures through 3D printing of active smart materials, typically shape memory polymers. A noteworthy aim of this research field is to obtain objects able to display complex shape‐shifting motions, such as sequential transformations over time. In this work, this peculiar response is studied on a commercial photopolymer, printed by stereolithography and featuring, on the basis of its inherent broad glass transition, the so‐called “temperature‐memory effect” (TME). The TME, that is, a response in which the shape memory effect occurs on a region controlled by the deformation temperature, is studied in shape memory cycles where the deformation temperature is systematically varied, so to provide a correlation between deformation and recovery temperatures. This also allows to properly select two temperatures at which deforming a specimen along a multistep history, so as to finally separate each recovery process on the temperature and time scales. This sequential recovery is studied in double folded bars, with arms deformed at different temperatures, and on a properly designed self‐locking clamp. The obtained results are promising for the realization of smart temperature‐responsive structures printed with one single polymer and capable of multiple shape transformations.
In this work, poly(ethylene glycol) (PEG)/poly(εcaprolactone) (PCL) semicrystalline networks were prepared by photo-cross-linking of methacrylated macromonomers with different molecular weights and in different proportions to obtain amphiphilic materials capable of displaying properly designed shape memory effects. Networks based on PCL 10 kDa and PEG 3 kDa showed suitable thermal and mechanical properties with well-separated crystallization and melting regions to achieve a self-standing two-way shape memory effect. Particularly, after the application of a specific thermomechanical history, these materials are capable of cyclically changing their shape between two configurations upon cooling−heating cycles in the absence of any external load applied. The effect of the composition of the networks and of the employed thermomechanical parameters, such as the applied strain and the actuation temperature, was investigated to shed light on the shape memory mechanism for this class of materials, which are considered promising for applications in the biomedical field and as reversible actuators for soft robotics.
The present paper aims at developing an integrated experimental/computational approach towards the design of shape memory devices fabricated by hot-processing with potential for use as gastroretentive drug delivery systems (DDSs) and for personalized therapy if 4D printing is involved.The approach was tested on a plasticized poly(vinyl alcohol) (PVA) of pharmaceutical grade, with a glass transition temperature close to that of the human body (i.e. 37 °C).A comprehensive experimental analysis was conducted in order to fully characterize the PVA thermomechanical response as well as to provide the necessary data to calibrate and validate the numerical predictions, based on a thermo-viscoelastic constitutive model, implemented within a finite element framework. Particularly, a thorough thermal, mechanical, and shape memory characterization under different testing conditions and on different sample geometries was first performed. Then, a prototype
Revised Manuscript UnmarkedClick here to view linked References 2 consisting of an S-shaped device was fabricated, deformed in a temporary compact configuration and tested. Simulation results were compared with the results obtained from shape memory experiments carried out on the prototype. The proposed approach provided useful results and recommendations for the design of PVA-based shape memory DDSs.
Retentive drug delivery systems (DDSs) are intended for prolonged residence and release inside hollow muscular organs, to achieve either local or systemic therapeutic goals. Recently, formulations based on shape memory polymers (SMPs) have gained attention in view of their special ability to recover a shape with greater spatial encumbrance at the target organ (e.g., urinary bladder or stomach), triggered by contact with biological fluids at body temperature. In this work, poly(vinyl alcohol) (PVA), a pharmaceutical-grade SMP previously shown to be an interesting 4D printing candidate, was employed to fabricate expandable organ-retentive prototypes by hot melt extrusion. With the aim of improving the mechanical resistance of the expandable DDS and slowing down relevant drug release, the application of insoluble permeable coatings based on either Eudragit® RS/RL or Eudragit® NE was evaluated using simple I-shaped specimens. The impact of the composition and thickness of the coating on the shape memory, swelling, and release behavior as well as on the mechanical properties of these specimens was thoroughly investigated and the effectiveness of the proposed strategy was demonstrated by the results obtained.
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