Farmacia y Tecnología Farmacéutica

URI permanente para esta comunidadhttps://hdl.handle.net/11441/11019

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3D-printed implants loaded with acriflavine for glioblastoma treatment
(Elsevier, 2024-09-12) Korelidou, Anna; Domínguez Robles, Juan; Islam, Rayhanul; Donnelly, Ryan F.; Coulter, Jonathan A.; Larrañeta, Eneko; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; European Union (UE). H2020; Agencia Estatal de Investigación. España; Ministerio de Ciencia e Innovación (MICIN). España
Drug delivery routes play an essential role in determining the efficacy and safety of medications. This study focused on the development and optimization of 3Dprinted reservoir type implants as a combinational therapy drug delivery system for Glioblastoma Multiforme (GBM) post-surgery, possessing also antibacterial properties. In this study, we used a multimodal agent, Acriflavine (ACF) as an alternative drug to treat GBM. To date, ACF is used only as an antiseptic agent, although it has been shown to possess strong anticancer activities. ACF and a low molecular weight PCL were loaded into 3D-printed reservoir-type implants for sustained drug delivery. The study demonstrated that ACF implants exhibited sustained drug release kinetics, with faster release during the initial 30 days, followed by a gradual decrease over 90 days. This controlled release profile enhances the effectiveness of ACF delivery to tumour targets while minimizing side effects associated with systemic administration. In vitro experiments confirmed the inhibitory activity of ACF against GBM cells compared to non-tumour cells. The study also highlighted the bacteriostatic effects of ACF, making the implants potentially useful for post-surgery infection management, particularly against S. aureus, a common bacterial infection associated with brain surgery. The long-term drug-release capabilities of the implants make them attractive candidates for both tumour inhibition and antibacterial treatment. The study suggests that the developed ACF delivery systems have the potential for future clinical studies. Their ability to provide increased drug efficacy without systemic toxicity makes them promising candidates for cancer therapy and post-surgery infection management.
Application of ultrasound-assisted compression and 3D-printing semi-solid extrusion techniques to the development of sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester
(Elsevier, 2024) Ferrero Rodríguez, Carmen; Urpí, Lourdes; Aguilar de Leyva, Mercedes Ángela; Mora Castaño, Gloria; Linares Blasco, Vicente; Millán Jiménez, Mónica; Martínez de Ilarduya, Antxon; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
The purpose of this study was to investigate the ability of two advanced hot-processing technologies, Ultrasound-Assisted Compression (USAC) and 3D-printing Semi-solid Extrusion (SSE), to manufacture sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester. The copolymer was synthesized from ω-pentadecalactone (PDL), 1,4-cyclohexanedimethanol (CHDM) and dimethyl succinate (DMS) (monomer ratio PDL/CHDM/DMS 70/30/30) by enzymatic ring opening polymerization and two-step melt polycondensation processes and has a random microstructure, a high molecular weight (107,100 g mol -1) and a relatively low melting point (~65 ◦C). The antibacterial agent metronidazole (MTZ) was chosen as model drug and binary physical mixtures copolymer:drug were prepared at 90:10 and 70:30 w/w ratios. Thermal analysis studies evidenced that the formulations could be processed below their degradation temperatures. Drug delivery devices with dense and meshed structures were manufactured using USAC and SSE techniques, respectively, with USAC devices exhibiting more reproducible physical properties than the SSE systems. Powder X-ray diffraction and scanning electron microscopy studies showed a partial sintering of the copolyester during USAC processing while MTZ remained mostly crystalline. In contrast, the copolymer melted and the drug underwent some amorphization when processed using SSE. In vitro drug release studies in phosphate buffer (pH 6.8) showed that, after an initial burst release of metronidazole, USAC and SSE devices exhibited a prolonged and/or sustained drug release over 20 days. The initial burst release was dependent on the manufacturing technique and the drug/polymer ratio, being minimized for SSE devices containing 10 wt% MTZ. The whole drug release profiles fitted well to the Peppas-Sahlin model, being drug diffusion the predominant release mechanism. After the burst release, the sustained release period of USAC and SSE devices containing 10 wt% MTZ showed a good fit to the zero-order kinetic model, with faster drug release from the SSE devices due to the larger surface area of their meshed structure. In conclusion, this work demonstrates that processing the aliphatic copolyester by both USAC and SSE technologies provides an attractive strategy to manufacture biodegradable drug delivery systems for long-term release of metronidazole.
Chitosan–Type-A-Gelatin Hydrogels Used as Potential Platforms in Tissue Engineering for Drug Delivery
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-07) Mehdi-Sefiani, Hanaa; Granados-Carrera, Carmen María; Romero García, Alberto; Chicardi Augusto, Ernesto; Domínguez Robles, Juan; Pérez-Puyana, Víctor Manuel; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Ingeniería y Ciencia de los Materiales y del Transporte; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; Universidad de Sevilla. TEP229: Tecnología y Diseño de Productos Multicomponentes; Universidad de Sevilla. TEP973: Tecnología de Polvos y Corrosión; Universidad de Sevilla. CTS547: Caracterización y Optimización Estadística de Medicamentos
Hydrogels are materials made of crosslinked 3D networks of hydrophilic polymer chains that can absorb and retain significant amounts of water due to their hydrophilic structure without being dissolved. In relation to alternative biomaterials, hydrogels offer increased biocompatibility and biodegradability, giving them distinct advantages. Thus, hydrogel platforms are considered to have the potential for the development of biomedical applications. In this study, the main objective was the development of hybrid hydrogels to act as a drug delivery platform. These hydrogels were made from chitosan (CH) and type A gelatin (G), two natural polymers that provide a supportive environment for cellular attachment, viability, and growth, thanks to their unique properties. Particularly, the use of gelatins for drug delivery systems provides biodegradability, biocompatibility, and non-toxicity, which are excellent properties to be used in the human body. However, gelatins have some limitations, such as thermal instability and poor mechanical properties. In order to improve those properties, the aim of this work was the development and characterization of hybrid hydrogels with different ratios of CH–G (100–0, 75–25, 50–50, 25–75, 0–100). Hydrogels were characterized through multiple techniques, including Fourier transform infrared (FTIR) spectroscopy, rheological and microstructural studies, among others. Moreover, a model hydrophilic drug molecule (tetracycline) was incorporated to evaluate the feasibility of this platform to sustain the release of hydrophilic drugs, by being tested in a solution of Phosphate Buffer Solution at a pH of 7.2 and at 37 °C. The results revealed that the synergy between chitosan and type A gelatin improved the mechanical properties as well as the thermal stability of it, revealing that the best ratios of the biopolymers are 50–50 CH–G and 75–25 CH–G. Thereby, these systems were evaluated in a controlled release of tetracycline, showing a controlled drug delivery of 6 h and highlighting their promising application as a platform for controlled drug release.
Hydrophilic High Drug-Loaded 3D Printed Gastroretentive System with Robust Release Kinetics
(Multidisciplinary Digital Publishing Institute (MDPI), 2023) Mora Castaño, Gloria; Millán Jiménez, Mónica; Caraballo, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Agencia Estatal de Investigación. España; Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España
Three-dimensional printing (3DP) technology enables an important improvement in the design of new drug delivery systems, such as gastroretentive floating tablets. These systems show a better temporal and spatial control of the drug release and can be customized based on individual therapeutic needs. The aim of this work was to prepare 3DP gastroretentive floating tablets designed to provide a controlled release of the API. Metformin was used as a non-molten model drug and hydroxypropylmethyl cellulose with null or negligible toxicity was the main carrier. High drug loads were assayed. Another objective was to maintain the release kinetics as robust as possible when varying drug doses from one patient to another. Floating tablets using 10–50% w/w drug-loaded filaments were obtained by Fused Deposition Modelling (FDM) 3DP. The sealing layers of our design allowed successful buoyancy of the systems and sustained drug release for more than 8 h. Moreover, the effect of different variables on the drug release behaviour was studied. It should be highlighted that the robustness of the release kinetics was affected by varying the internal mesh size, and therefore the drug load. This could represent a step forward in the personalization of the treatments, a key advantage of 3DP technology in the pharmaceutical field.
Nanotechnologies for the delivery of biologicals: Historical perspective and current landscape
(Elsevier, 2021) Durán Lobato, María Matilde; López Estévez, Ana María; Cordeiro, Ana Sara; Dacoba, Tamara G.; Crecente Campo, José; Torres, Dolores; Alonso, María José; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Xunta de Galicia; Agencia Estatal de Investigación. España
Biological macromolecule-based therapeutics irrupted in the pharmaceutical scene generating a great hope due to their outstanding specificity and potency. However, given their susceptibility to degradation and limited capacity to overcome biological barriers new delivery technologies had to be developed for them to reach their targets. This review aims at analyzing the historical seminal advances that shaped the development of the protein/peptide delivery field, along with the emerging technologies on the lead of the current landscape. Particularly, focus is made on technologies with a potential for transmucosal systemic delivery of protein/peptide drugs, followed by approaches for the delivery of antigens as new vaccination strategies, and formulations of biological drugs in oncology, with special emphasis on mAbs. Finally, a discussion of the key challenges the field is facing, along with an overview of prospective advances are provided.
Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems
(MDPI, 2022) Ferrero Rodríguez, Carmen; Casas Delgado, Marta; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Stimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox·HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG–PDH–mPEG) was synthesized with a central hydrophobic block containing disulfide linkages and two hydrophilic segments of poly(ethylene glycol) methyl ether. Taking advantage of the self-assembly of this amphiphilic copolymer in aqueous solution, in the present investigation we introduce a solvent-exchange method that simultaneously achieves polymersome formation and drug loading in phosphate buffer saline (10 mM, pH 7.4). Blank and drug-loaded polymersomes (5 and 10 wt.% feeding ratios) were prepared and characterized for morphology, particle size, surface charge, encapsulation efficiency and drug release behavior. Spherical vesicles of uniform size (120–190 nm) and negative zeta potentials were obtained. Dox·HCl was encapsulated into polymersomes with a remarkably high efficiency (up to 98 wt.%). In vitro drug release studies demonstrated a prolonged and diffusion-driven release at physiological conditions (~34% after 48 h). Cleavage of the disulfide bonds in the presence of 50 mM glutathione (GSH) enhanced drug release (~77%) due to the contribution of the erosion mechanism. Therefore, the designed polymersomes are promising candidates for selective drug release in the reductive environment of cancer cells.
Reservoir-Type Subcutaneous Implantable DevicesContaining Porous Rate Controlling Membranes forSustained Delivery of Risperidone
(Wiley, 2025-01-16) Li, Linlin; Permana, Andi Dian; Domínguez Robles, Juan; Amir, Muh Nur; Habibie, Habibie; Anjani, Qonita Kurnia; Larrañeta, Eneko; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). España
Implantable drug delivery systems are crucial for achieving sustained deliveryof active compounds to speciﬁc sites or systemic circulation. In this study, anovel reservoir-type implant combining a biodegradable rate-controllingmembrane with a drug-containing core prepared using direct compressiontechniques is developed. The membrane is composed of poly(caprolactone)(PCL), and risperidone (RIS) served as the model drug. Characterization ofboth membranes and direct compressed pellets includes hardness testing,optical coherence tomography, mercury intrusion porosimetry, and surfacemorphology observation. In vitro release studies of RIS reveal that higher drugloading in the pellets extended-release duration up to 70 days whenincorporated into membranes with four layers. Increasing the number ofmembrane layers slows the release rate further, ranging from 70 to 170 daysdepending on membrane thickness. Biocompatibility studies demonstratethat these implantable devices are non-toxic and biocompatible with cells invitro. In vivo studies conduct in male Wistar rats demonstrate sustainedrelease of RIS, with plasma levels showing a signiﬁcant increasepost-implantation at a relatively constant rate for up to 49 days. These resultsindicate that the developed implants have the potential to provide long-actingdrug delivery to the systemic circulation.

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Examinando Farmacia y Tecnología Farmacéutica por Agencia financiadora "Agencia Estatal de Investigación. España"