Alexander Parra Coca


LÍNEAS DE INVESTIGACIÓN:   Nanoparticulas, farmacología, toxicología, residuos de medicamentos

FACULTAD:  Ciencias Agropecuarias



Médico Veterinario Zootecnista de la Universidad de la Amazonía; Maestría en Investigación Desarrollo y Control de Medicamentos (Farmacología). Universidad de Barcelona (España); Doctorado en Investigación Desarrollo y Control de Medicamentos (Farmacología). Universidad de Barcelona (España). Instructor durante dos años en el Servicio Nacional de Aprendizaje (SENA) en el área pecuaria. Experiencia de 12 años como veterinario clínico, tanto en consulta, como anestesia y cirugía, en diferentes clínicas veterinarias de Madrid y Barcelona (España).

Investigador (práctica de Maestría), tiempo completo. Áreas/temas relacionados: Modelos de dolor in vivo, screening de medicamentos, inmunohistoquímica, biomarcadores en analgesia; departamento in vivo analgesia, Laboratorio Farmacéutico Esteve, Barcelona. Investigador (práctica de Doctorado), tiempo completo. Áreas/temas relacionados: Diálisis/permeación de fármacos mediante la técnica de las Células de Difusión de Franz, estudio de fármacos por Cromatografía Líquida (HPLC y UPLC), diferentes técnicas analíticas de medicamentos, elaboración de medicamentos semisólidos, elaboración de nutracéuticos; departamento de I+D, área de semisólidos, Laboratorio Farmacéutico Reig Jofrè, Barcelona. Áreas de investigación y de interés: Farmacología, anestesia, clínica, toxicología, cromatografía, nanotecnología, estudios de permeación de medicamentos, farmacocinética, residuos de medicamentos. Procurar de que el estudiante se forme de manera integral inculcando su capacidad crítica, proyectar al estudiante para que desarrolle habilidades y destrezas en las áreas de interés.


Validation of a high performance liquid chromatography method for the stabilization of epigallocatechin gallate
Fecha de publicación: 20/11/2014

Epigallocatechin gallate (EGCG) is a green tea catechin with potential health benefits, such as anti-oxidant, anti-carcinogenic and anti-inflammatory effects. In general, EGCG is highly susceptible to degradation, therefore presenting stability problems. The present paper was focused on the study of EGCG stability in HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid) medium regarding the pH dependency, storage temperature and in the presence of ascorbic acid a reducing agent. The evaluation of EGCG in HEPES buffer has demonstrated that this molecule is not able of maintaining its physicochemical properties and potential beneficial effects, since it is partially or completely degraded, depending on the EGCG concentration. The storage temperature of EGCG most suitable to maintain its structure was shown to be the lower values (4 or −20 °C). The pH 3.5 was able to provide greater stability than pH 7.4. However, the presence of a reducing agent (i.e., ascorbic acid) was shown to provide greater protection against degradation of EGCG. A validation method based on RP-HPLC with UV–vis detection was carried out for two media: water and a biocompatible physiological medium composed of Transcutol®P, ethanol and ascorbic acid. The quantification of EGCG for purposes, using pure EGCG, requires a validated HPLC method which could be possible to apply in pharmacokinetic and pharmacodynamics studies.

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Nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) for retinyl palmitate: Effect on skin permeation
Fecha de publicación: 01/10/2014

The aim of this study was to develop biocompatible lipid-based nanocarriers for retinyl palmitate (RP) to improve its skin delivery, photostability and biocompatibility, and to avoid undesirable topical side effects. RP loaded nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) were characterized in terms of size, surface electrical charge, pH, drug encapsulation efficiency and morphology. Spherical-shaped nanocarriers with a negatively charged surface (>|40| mV) and mean size lower than 275 nm were produced with adequate skin compatibility. The rheological properties showed that aqueous dispersions of SLNs followed a non-Newtonian behavior, pseudoplastic fluid adjusted to Herschel–Bulkley equation, whereas LPs and NEs exhibited a Newtonian behavior. SLNs offered significantly better photoprotection than LPs and NEs for RP. The cumulative amount of drug permeated through human skin at the end of 38 h was 6.67 ± 1.58 μg, 4.36 ± 0.21 μg and 3.64 ± 0.28 μg for NEs, LPs and SLNs, respectively. NEs flux was significantly higher than SLNs and LPs: NEs (0.37 ± 0.12 μg/h) > LPs (0.15 ± 0.09 μg/h) > SLNs (0.10 ± 0.05 μg/h). LPs offered significant higher skin retention than NEs and SLNs. Finally, even though all developed nanocarriers were found to be biocompatible, according to histological studies, NE was the system that most disrupted the skin. These encouraging findings can guide in proper selection of topical carriers among the diversity of available lipid-based nanocarriers, especially when a dermatologic or cosmetic purpose is desired.

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Influence of freeze-drying and γ-irradiation in preclinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using d-(+)-trehalose and polyethylene glycol
Fecha de publicación: 23/08/2016

This study investigated the suspension of poly(ε-caprolactone) nanoparticles as an ocular delivery system for flurbiprofen (FB-PεCL-NPs) in order to overcome the associated problems, such as stability, sterility, tolerance, and efficacy, with two different FB-PεCL-NP formulations. The formulations were stabilized with poloxamer 188 (1.66% and 3.5%) and submitted individually for freeze-drying and γ-irradiation with polyethylene glycol 3350 (PEG3350) and d-(+)-trehalose (TRE). Both formulations satisfied criteria according to all physicochemical parameters required for ocular pharmaceuticals. The FB-PεCL-NP formulations showed non-Newtonian behavior and sustained drug release. Ex vivo permeation analysis using isolated ocular pig tissues suggested that the presence of PEG3350 results in a reduction of FB transcorneal permeation. Moreover, TRE improved the penetration of FB across the cornea, especially after γ-irradiation. In addition, both formulations did not show a significant affinity in increasing FB transscleral permeation. Both formulations were classified as nonirritating, safe products for ophthalmic administration according to hen’s egg test-chorioallantoic membrane and Draize eye test. Furthermore, an in vivo anti-inflammatory efficacy test showed that irradiated FB-PεCL-NPs prepared with PEG3350 (IR-NPsPEG) have longer anti-inflammatory effects than those presented with irradiated FB-PεCL-NPs prepared with TRE (IR-NPsTRE). IR-NPsPEG showed a suitable physical stability after an aqueous reconstitution over >30 days. This study concludes that both formulations meet the Goldman’s criteria and demonstrate how irradiated nanoparticles, with innovative permeation characteristics, could be used as a feasible alternative to a flurbiprofen solution for ocular application in clinical trials.

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Ex vivo permeation of carprofen from nanoparticles: A comprehensive study through human, porcine and bovine skin as anti-inflammatory agent
Fecha de publicación: 30/03/2016

The purpose of this study was the development of poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) for the dermal delivery of carprofen (CP). The developed nanovehicle was then lyophilized using hydroxypropyl-β-cyclodextrin (HPβCD) as cryoprotectant. The ex vivo permeation profiles were evaluated using Franz diffusion cells using three different types of skin membranes: human, porcine and bovine. Furthermore, biomechanical properties of skin (trans-epidermal water loss and skin hydration) were tested. Finally, the in vivo skin irritation and the anti-inflammatory efficacy were also assayed. Results demonstrated the achievement of NPs 187.32 nm sized with homogeneous distribution, negatively charged surface (−23.39 mV) and high CP entrapment efficiency (75.38%). Permeation studies showed similar diffusion values between human and porcine skins and higher for bovine. No signs of skin irritation were observed in rabbits. Topically applied NPs significantly decreased in vivo inflammation compared to the reference drug in a TPA-induced mouse ear edema model. Thus, it was concluded that NPs containing CP may be a useful tool for the dermal treatment of local inflammation.

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Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: ocular anti-inflammatory applications
Fecha de publicación: 01/12/2015

This work aimed the design and development of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) for the ocular delivery of Carprofen (CP) by a central rotatable composite design 23+ star. NPs showed adequate size for ocular administration (189.50 ± 1.67 nm), low polydispersity (0.01 ± 0.01), negative charge surface (–22.80 ± 0.66 mV) and optimal entrapment efficiency (74.70 ± 0.95%). Physicochemical analysis confirmed that CP was dispersed inside the NPs. The drug release followed a first order kinetic model providing greater sustained CP release after lyophilization. Ex vivo permeation analysis through isolated rabbit cornea revealed that a sufficient amount of CP was retained in the tissue avoiding excessive permeation and thus, potential systemic levels. Ex vivo ocular tolerance results showed no signs of ocular irritancy, which was also confirmed by in vivo Draize test. In vivo ocular anti-inflammatory efficacy test confirmed an optimal efficacy of NPs and its potential application in eye surgery.

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