Small-diameter synthetic vascular grafts are required for surgical bypass grafting when there is a lack of suitable autologous vessels due to different reasons, such as previous operations. Thrombosis is the main cause of failure of small-diameter synthetic vascular grafts when used for this revascularization technique. Therefore, the development of biodegradable vascular grafts capable of providing a localized and sustained antithrombotic drug release mark a major step forward in the fight against cardiovascular diseases, which are the leading cause of death globally. The present paper describes the use of an extrusion-based 3D printing technology for the production of biodegradable antiplatelet tubular grafts for cardiovascular applications. For this purpose, acetylsalicylic acid (ASA) was chosen as a model molecule due to its antiplatelet activity. Poly(caprolactone) and ASA were combined for the fabrication and characterization of ASA-loaded tubular grafts. Moreover, rifampicin (RIF) was added to the formulation containing the higher ASA loading, as a model molecule that can be used to prevent vascular prosthesis infections. The produced tubular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet and antimicrobial activity and cytocompatibility. The results suggested that these materials were capable of providing a sustained ASA release for periods of up to 2 weeks. Tubular grafts containing 10% (w/w) of ASA showed lower platelet adhesion onto the surface than the blank and grafts containing 5% (w/w) of ASA. Moreover, tubular grafts scaffolds containing 1% (w/w) of RIF were capable of inhibiting the growth of Staphylococcus aureus. Finally, the evaluation of the cytocompatibility of the scaffold samples revealed that the incorporation of ASA or RIF into the composition did not compromise cell viability and proliferation at short incubation periods (24 h).
Implantable drug delivery systems offer an alternative for the treatments of long-term conditions (i.e. schizophrenia, HIV, or Parkinson’s disease among many others). The objective of the present work was to formulate implantable devices loaded with the model hydrophobic drug olanzapine (OLZ) using robocasting 3D-printing combined with a pre-formed rate controlling membrane. OLZ was selected as a model molecule due to its hydrophobic nature and because is a good example of a molecule used to treat a chronic condition schizophrenia. The resulting implants consisted of a poly(ethylene oxide) (PEO) implant coated with a poly(caprolactone) (PCL)-based membrane. The implants were loaded with 50 and 80% (w/w) of OLZ. They were prepared using an extrusion-based 3D-printer from aqueous pastes containing 36–38% (w/w) of water. The printing process was carried out at room temperature. The resulting implants were characterized by using infrared spectroscopy, scanning electron microscopy, thermal analysis, and X-ray diffraction. Crystals of OLZ were present in the implant after the printing process. In vitro release studies showed that implants containing 50% and 80% (w/w) of OLZ were capable of providing drug release for up to 190 days. On the other hand, implants containing 80% (w/w) of OLZ presented a slower release kinetics. After 190 days, total drug release was ca. 77% and ca. 64% for implants containing 50% and 80% (w/w) of OLZ, respectively. The higher PEO content within implants containing 50% (w/w) of OLZ allows a faster release as this polymer acts as a co-solvent of the drug.
1 September 2021 in International Journal of Pharmaceutics
Rose Bengal (RB) holds promise for therapeutic applications in the gastrointestinal (GI) tract but faces significant limitations due to poor bioavailability and stability in the GI environment. This in vitro proof-of-concept study aimed to develop an oral drug delivery system using self-assembled RB–chitosan (RBCS) nanocomposites formed via electrostatic interactions. RBCS nanocomposites exhibited high drug loading efficiency (87%) and a uniform particle size (~443 nm), with physicochemical analyses confirming molecular interactions and structural stability. However, in vitro studies revealed poor and highly variable drug release in simulated gastric fluids (SGFs), underlining the need for further optimization. To address these limitations, RBCS nanocomposites were encapsulated within well-established alginate beads (AlgBs). Among the tested systems, RBCS20-AlgBs were selected as the optimal one, forming a gastroresistant platform. Encapsulation mitigated burst release, enhanced structural integrity, and enabled sustained RB release under intestinal conditions. Swelling studies demonstrated that RBCS20-AlgBs maintained controlled hydration, preventing premature disintegration. Mathematical modeling indicated a matrix relaxation-driven release mechanism, with RBCS20-AlgBs demonstrating improved reproducibility compared to RB-loaded AlgBs (RB-AlgBs). Future studies should focus on evaluating in vivo performance to confirm the system’s efficacy for oral administration.
This interdisciplinary work, which integrates teaching, research and extension, incorporated students from 5 Latin American universities of Architecture and dif...
Implantable drug delivery systems are presented as a potential alternative to current treatments of chronic conditions. The aim of this work was to formulate a subcutaneous implantable device made with prefabricated poly(caprolactone) (PCL) cylinders, loaded with olanzapine (OLZ) as a model drug and cyclodextrin in a mass ratio of 1:1. The final formulation was characterized using optical microscopy, infrared spectroscopy, thermal analysis, and X-ray diffraction. The proposed device was successfully fabricated and demonstrated ability to control drug release for 60 days. With continued development, these novel implants could be an alternative to currently available treatments for schizophrenia.