Person: Heras Polo, Beatriz De Las
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First Name
Beatriz De Las
Last Name
Heras Polo
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Farmacología, Farmacognosia y Botánica
Area
Farmacología
Identifiers
4 results
Search Results
Now showing 1 - 4 of 4
Item Amphiphilic Acrylic Nanoparticles Containing the Poloxamer Star Bayfit® 10WF15 as Ophthalmic Drug Carriers(Polymers, 2019) Gómez Ballesteros, Miguel; Andrés Guerrero, Vanesa; Parra Luna, Francisco; Marinich, Jorge; Heras Polo, Beatriz De Las; Molina Martínez, Irene Teresa; Vázquez Lasa, Blanca; San Román Del Barrio, Julio; Herrero Vanrell, María Del RocíoTopical application of drops containing ocular drugs is the preferred non-invasive route to treat diseases that a_ect the anterior segment of the eye. However, the formulation of eye drops is a major challenge for pharmacists since the access of drugs to ocular tissues is restricted by several barriers. Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used orally for the treatment of ocular hypertension in glaucoma. However, large ACZ doses are needed which results in systemic side e_ects. Recently, we synthesized copolymers based on 2-hydroxyethyl methacrylate (HEMA) and a functionalized three-arm poloxamer star (Bayfit-MA). The new material (HEMA/Bayfit-MA) was engineered to be transformed into nanoparticles without the use of surfactants, which represents a significant step forward in developing new ophthalmic drug delivery platforms. Acetazolamide-loaded nanocarriers (ACZ-NPs) were prepared via dialysis (224 +/- 19 nm, ̶ 17.2 +/- 0.4 mV). The in vitro release rate of ACZ was constant over 24 h (cumulative delivery of ACZ: 83.3 +/- 8.4%). Following standard specifications, ACZ-NPs were not cytotoxic in vitro in cornea, conjunctiva, and macrophages. In normotensive rabbits, ACZ-NPs generated a significant intraocular pressure reduction compared to a conventional solution of ACZ (16.4% versus 9.6%) with the same dose of the hypotensive drug (20 μg). In comparison to previously reported studies, this formulation reduced intraocular pressure with a lower dose of ACZ. In summary, HEMA:Bayfit-MA nanoparticles may be a promising system for ocular topical treatments, showing an enhanced ocular bioavailability of ACZ after a single instillation on the ocular surface.Item Novel Nano-Liposome Formulation for Dry Eyes with Components Similar to the Preocular Tear Film(Polymers, 2018) Vicario De La Torre, Marta; Caballo González, María; Vico Ruiz, Eva; Morales Fernández, Laura; Arriola Villalobos, Pedro; Heras Polo, Beatriz De Las; Benítez Del Castillo Sánchez, José Manuel; Guzmán Navarro, Manuel; Millar, Thomas; Herrero Vanrell, María Del Rocío; Molina Martínez, Irene TeresaDry eye is commonly treated with artificial tears; however, developing artificial tears similar to natural tears is difficult due to the complex nature of tears. We characterized and evaluated a novel artificial tear formulation with components similar to the lipid and aqueous constituents of natural tears. Nano-liposomes, composed in part of phosphatidylcholine, were dispersed in an aqueous solution of bioadhesive sodium hyaluronate. Liposome size, zeta potential, and physicochemical properties of the fresh and stored (4°C) liposomal formulation were analyzed. In vitro tolerance was tested using human corneal and conjunctival cell lines by exposures of 15 min to 4 h. The tolerance of the liposomal formulation was evaluated in animals (rabbits). The average liposome size was 186.3 +/- 7.0 nm, and the zeta potential was negative. The osmolarity of the formulation was 198.6 +/- 1.7 mOsm, with a surface tension of 36.5 +/- 0.4 mN/m and viscosity of 3.05 +/- 0.02 mPa·s. Viability values in the human corneal and conjunctival cell lines were always >80%, even after liposomal formulation storage for 8 weeks. Discomfort and clinical signs after instillation in rabbit eyes were absent. The new formulation, based on phosphatidylcholine-liposomes dispersed in sodium hyaluronate has suitable components and characteristics, including high in vitro cell viability and good in vivo tolerance, to serve as a tear substitute.Item Design and characterization of an ocular topical liposomal preparation to replenish the lipids of the tear film(Investigative Ophthalmology & Visual Science, 2014) Vicario De La Torre, Marta; Benítez Del Castillo Sánchez, José Manuel; Vico Ruiz, Eva; Guzmán Pastor, Manuel; Heras Polo, Beatriz De Las; Herrero Vanrell, María Del Rocío; Molina Martínez, Irene TeresaPurpose: Dry eye (DE) includes a group of diseases related to tear film disorders. Current trends for DE therapy focus on providing lipid components to replace the damaged lipid layer. Formulations that contain aqueous and mucin like compounds may have additional therapeutic benefits for DE patients. The aim of this work was to design and evaluate novel formulations having the potential to become topical treatment for DE. Methods: Unpreserved liposomal formulations composed of phosphatidylcholine (PC), cholesterol, and α tocopherol (vit E) were prepared by the thin-film hydration technique. Formulations were characterized in terms of liposome size, pH, surface tension, osmolarity, and viscosity. In vitro tolerance assays were performed on macrophage, human corneal and conjunctival cell lines at short and long term exposures. In vivo ocular tolerance was studied after instillation of the formulation. Results: The mean liposome size was less than 1 μm and surface tension <30 50 mN/m for all formulations. The final liposomal formulation (PC:cholesterol:vit E in a ratio 8:1:0.8) had physiological values of pH (6.45 ± 0.09), osmolarity (289.43 ± 3.28 mOsm), and viscosity (1.82 ± 0.02 mPa·s). Cell viability was greater than 80% in the corneal and conjunctival cells. This formulation was well tolerated by experimental animals. Conclusions: The unpreserved liposomal formulation has suitable properties to be administered by topical ophthalmic route. The liposome-based artificial tear had good in vitro and in vivo tolerance responses. This formulation composed of a combination of liposomes and bioadhesive polymers may be employed successfully as a tear film substitute in DE therapy.Item Novel water-soluble mucoadhesive carbosilane dendrimers for ocular administration(Molecular Pharmaceutics, 2016) Bravo Osuna, Irene; Vicario De La Torre, Marta; Andrés Guerrero, Vanesa; Sánchez Nieves, Javier; Guzmán Navarro, Manuel; Matad, F. Javier De La; Gómez Aspe, Rafael; Heras Polo, Beatriz De Las; Argüesoh, Pablo; Poncheli, Gilles; Herrero Vanrell, María Del Rocío; Molina Martínez, Irene TeresaPurpose: To determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (Generations 1-3) as mucoadhesive polymers in eyedrop formulations. Methods: Cationic carbosilane dendrimers decorated with ammonium –NH3 + groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. Results: The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral –NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 μM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 μM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0 8h and maximal intraocular pressure reduction. Conclusion: This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.