Person:
Bravo Osuna, Irene

First Name

Irene

Last Name

Bravo Osuna

URI

https://hdl.handle.net/20.500.14352/77583

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Farmacia Galénica y Tecnología Alimentaria

Area

Farmacia y Tecnología Farmaceútica

Identifiers

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Search Results

Now showing 1 - 10 of 17

Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration
(European Journal of Pharmaceutical Sciences, 2016) Rodríguez Villanueva, Javier; Bravo Osuna, Irene; Herrero Vanrell, María Del Rocío; Molina Martínez, Irene Teresa; Guzmán Navarro, M.
Successful therapy for chronic diseases affecting the posterior segment of the eye requires sustained drug concentrations at the site of action for extended periods of time. To achieve this, it is necessary to use high systemic doses or frequent intraocular injections, both associated with serious adverse effects. In order to avoid these complications and improve patient`s quality of life, an experimental study has been conducted on the preparation of a new generation of biodegradable poly D-L(lactide-co-glycolide (50:50) (PLGA) polymer microspheres (MSs) loaded with Dxm, vitamin E and/or human serum albumin (HSA). Particles were prepared according to a S/O/W encapsulation method and the 20-40μm fraction was selected. This narrow size distribution is suitable for minimally invasive intravitreal injection by small calibre needles. Characterisation of the MSs showed high Dxm loading and encapsulation efficiency (> 90%) without a strong interaction with the polymer matrix, as revealed by DSC analysis. MSs drug release studies indicated a small burst effect (lower than 5%) during the first five hours and subsequently, drug release was sustained for at least 30 days, led by diffusion and erosion mechanisms. Dxm release rate was modulated when solid state HSA was incorporated into MSs formulation. SDS-PAGE analysis showed that the protein maintained its integrity during the encapsulation process, as well as for the release study. MSs presented good tolerance and lack of cytotoxicity in macrophages and HeLa cultured cells. After 12 months of storage under standard refrigerated conditions (41ºC), MSs retained appropriate physical and chemical properties and analogous drug release kinetics. Therefore, we conclude that these microspheres are promising pharmaceutical systems for intraocular administration, allowing controlled release of the drug.
Project number: 215
Diseño de herramientas para la adquisición de competencias transversales CT9, CT11, CT12 y CT13 que fomenten el desarrollo de habilidades de aplicación en la formación y competencia laboral de alumnos del Grado en Farmacia
(2018) Gil Alegre, María Esther; Molina Martínez, Irene Teresa; Pastoriza Abal, María Pilar; Herrero Vanrell, María Del Rocío; Bravo Osuna, Irene; Ruiz Caro, Roberto; Arranz Romera, Alicia
A través de las competencias transversales comunes al Grado en Farmacia y a la materia Tecnología Farmacéutica se pretende dotar a los alumnos de herramientas para el desarrollo de habilidades necesarias en sus estudios y en su empleabilidad.
Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina
(Advanced Drug Delivery Reviews, 2018) Bravo Osuna, Irene; Andrés-Guerrero, Vanessa; Arranz Romera, Alicia; Esteban Pérez, Sergio; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío
Pathologies affecting the optic nerve and the retina are one of the major causes of blindness. These diseases include age-related macular degeneration (AMD), diabetic Retinopathy (DR) and glaucoma, among others. Also, there are genetic disorders that affect the retina causing visual impairment. The prevalence of neurodegenerative diseases of the posterior segment are increased as most of them are related with the elderly. Even with the access to different treatments, there are some challenges in managing patients suffering retinal diseases. One of them is the need for frequent interventions. Also, an unpredictable response to therapy has suggested that different pathways may be playing a role in the development of these diseases. The management of these pathologies requires the development of controlled drug delivery systems able to slow the progression of the disease without the need of frequent invasive interventions, typically related with endophthalmitis, retinal detachment, ocular hypertension, cataract, inflammation, and floaters, among other. Biodegradable microspheres are able to encapsulate low molecular weight substances and large molecules such as biotechnological products. Over the last years, a large variety of active substances has been encapsulated in microspheres with the intention of providing neuroprotection of the optic nerve and the retina. The purpose of the present review is to describe the use of microspheres in chronic neurodegenerative diseases affecting the retina and the optic nerve. The advantage of microencapsulation of low molecular weight drugs as well as therapeutic peptides and proteins to be used as neuroprotective strategy is discussed. Also, a new use of the microspheres in the development of animal models of neurodegeneration of the posterior segment is described.
Pharmaceuticalmicroscale and nanoscale approaches for efficient treatment of ocular diseases
(Drug Delivery and Translational Research, 2016) Bravo Osuna, Irene; Andrés Guerrero, Vanesa; Pastoriza Abal, María Pilar; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío
Efficient treatment of ocular diseases can be achieved thanks to the proper use of ophthalmic formulations based on emerging pharmaceutical approaches. Among them, microtechnology and nanotechnology strategies are of great interest in the development of novel drug delivery systems to be used for ocular therapy. The location of the target site in the eye as well as the ophthalmic disease will determine the route of administration (topical, intraocular, periocular, and suprachoroidal administration) and the most adequate device. In this review, we discuss the use of colloidal pharmaceutical systems (nanoparticles, liposomes, niosomes, dendrimers, and microemulsions), microparticles (microcapsules and microspheres), and hybrid systems (combination of different strategies) in the treatment of ophthalmic diseases. Emphasis has been placed in the therapeutic significance of each drug delivery system for clinical translation.
CHAPTER 10: Drug Delivery Systems for the Treatment of Diseases Affecting the Retina and Optic Nerve.
(Therapies for Retinal Degeneration: Targeting Common Processes, 2018) Bravo Osuna, Irene; Andrés Guerrero, Vanesa; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío; De la Rosa, Enrique J.; Cotter, Thomas G.
Diseases affecting the retina and the optic nerve are the major causes of irreversible blindness in the elderly population. Succesful therapy of these pathologies requires frequent administration of the active molecule close to the retinal target site. Intraocular drug delivery systems (IDDS) are emerging therapeutic tools in the treatment of diseases affecting the posterior segment, as they are able to provide effective concentrations of the drug for a long period, thus avoiding successive injections. Depending on their size, IDDS are classified in implants, microsystems and nanosystems. This chapter covers a general description of the IDDS useful for the treatment of diseases affecting retinal structures. © The Royal Society of Chemistry 2019.
Nano and microtechnologies for ophthalmic administration. An overview
(Journal of Drug Delivery Science and Technology, 2013) Herrero Vanrell, María Del Rocío; Vicario De La Torre, Marta; Andrés-Guerrero, Vanessa; Barbosa-Alfaro, Deyanira; Molina Martínez, Irene Teresa; Bravo Osuna, Irene
Ocular drug delivery is one of the most challenging fields of pharmaceutical research. They are generally employed to overcome the static (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) and dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) of the eye. Ophthalmic formulations must be sterile, and the biomaterials used in the preparation of pharmaceutical systems completely compatible and extremely well tolerated by ocular tissues. The location of the target tissue in the eye will determine the route of administration. Ophthalmic administration systems are intended for topical, intraocular and periocular administration. In this review we describe the main pharmaceutical nano- and microsystems currently under study to administrate drugs in the eye, covering microparticles, nanoparticles, liposomes, microemulsions, niosomes and dendrimers. We have performed the corresponding revision of the published scientific literature always emphasizing the technological aspects. The review discusses also the biomaterials used in the preparation of the nano and microsystems of ophthalmic drug delivery, fabrication techniques, therapeutic significances, and future possibilities in the field.
Simultaneous co-delivery of neuroprotective drugs from multiloaded PLGA microspheres for the treatment of glaucoma
(Journal of Controlled Release, 2019) Arranz Romera, Alicia; Davis, Benjamin M.; Bravo Osuna, Irene; Esteban Pérez, Sergio; Molina Martínez, Irene Teresa; Shamsher, Ehtesham; Ravindran, Nivedita; Guo, Li; Cordeiro, M. Francesca; Herrero Vanrell, María Del Rocío
Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ± 1.89 μm rendering them suitable for intravitreal injection using conventional 25G-32G needles. Greater than 62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC50 10.00±0.94 mM versus 6.89±0.82 mM in absence of DMQ-MSs) in R28 cell line. In vivo efficacy studies were performed using a well-established rodent model of chronic ocular hypertension (OHT), comparing single intravitreal injections of microspheres of DMQ-MSs to their equivalent individual single drug loaded MSs mixture (MSsmix), empty MSs, no-treatment OHT only and naïve groups. Twenty one days after OHT induction, DMQ-MSs showed a significantly neuroprotective effect on RGCs compared to OHT only controls. No such protective effect was observed in empty MSs and single-drug MSs treated groups. This work suggests that multi-loaded PLGA MSs present a novel therapeutic approach in the management of retinal neurodegeneration conditions such as glaucoma.
Trojan Microparticles Potential for Ophthalmic Drug Delivery
(Current Medicinal Chemistry, 2019) Esteban Pérez, Sergio; Bravo Osuna, Irene; Andrés Guerrero, Vanesa; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío
The administration of drugs to treat ocular disorders still remains a technological challenge in this XXI century. Although there is an important arsenal of active molecules useful to treat ocular diseases, ranging from classical compounds to biotechnological products, currenty, no ideal delivery system is able to profit all their therapeutic potential. Among the intraocular drug delivery systems (IODDS) proposed to overcome some of the most important limitations, microsystems and nanosystems have raised high attention. While microsystems are able to offer long-term release after intravitreal injection, nanosystems can protect the active compound from external environment (reducing their clearance) and direct it to its target tissues. In recent years, some researchers have explored the possibility of combining micro and nanosystems in “nanoparticle-in-microparticle (NiMs)” systems or “trojan systems”. This excellent idea is not exempt of technological problems, remains partially unsolved, especially in the case of IODDS. The objective of the present review is to show the state of art concerning the design, preparation and characterization of trojan microparticles for drug delivery and to remark their potential and limitations as IODDS, one of the most important challenges faced by pharmaceutical technology at the moment.
Project number: 349
Competencias TIC del alumnado en el ámbito docente de la Tecnología Farmacéutica I: diseño de actividades para su fomento, elaboración de un primer catálogo y definición de indicadores y niveles de dominio.
(2016) Gil Alegre, María Esther; Molina Martínez, Irene Teresa; Veiga Ochoa, María Dolores; Pastoriza Abal, María Pilar; Herrero Vanrell, María Del Rocío; Bravo Osuna, Irene; Ruiz Caro, Roberto
The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies
(Progress in Retinal and Eye Research, 2014) Herrero Vanrell, María Del Rocío; Bravo Osuna, Irene; Andrés-Guerrero, Vanessa; Vicario De La Torre, Marta; Molina Martínez, Irene Teresa
Pathologies affecting the posterior segment are one of the major causes of blindness in developed countries and are becoming more prevalent due to the increase in society longevity. Sucessful therapy of diseases affecting the back of the eye requires effective concentrations of the active substance mantained during a long period of time in the intraocular target site. Treatment of vitreoretinal diseases often include repeated intravitreous injections that are associated with adverse effects. Local administration of biodegradable microspheres offers an excellent alternative to multiple administrations, as they are able to deliver the therapeutic molecule in a controlled fashion. Furthermore, injection of microparticles is performed without the need for surgical procedures. As most of the retinal diseases are multifactorial, microspheres result especially promising because they can be loaded with more than one active substance and complemented with the inclusion of additives with pharmacological properties. Personalized therapy can be easily achieved by changing the amount of administered microspheres. Contrary to non-biodegradable devices, biodegradable PLA and PLGA microspheres disappear from the site of administration after delivering the drug. Furthermore, microspheres prepared from these mentioned biomaterials are well tolerated after periocular and intravitreal injections in animals and humans. After injection, PLA and PLGA microspheres suffer aggregation behaving like an implant. Biodegradable microspheres are potential tools in regenerative medicine for retinal repair. According to the reported results, presumably a variety of microparticulate formulations for different ophthalmic therapeutic uses will be available in the clinical practice in the near future.