title: Design and optimization of oleanolic/ursolic acid-loaded nanoplatforms for ocular anti-inflammatory applications.
abstract: Oleanolic acid (OA) and ursolic acid (UA) are ubiquitous pentacyclic triterpenes compounds in plants with great interest as anti-inflammatory therapeutics. The aim of this study was the design and optimization of polymeric nanoparticles (NPs) loaded with natural and synthetic mixtures (NM, SM) of these drugs for ophthalmic administration. A 2(3) + star central rotatable composite design was employed to perform the experiments. Results showed optimal and stable formulations with suitable physicochemical properties (mean diameter<225 nm), homogeneous distribution (polydispersity index∼0.1), negatively charged surface (∼-27 mV) and high entrapment efficiency (∼77%). Release and corneal permeation studies showed that NM release was faster than SM. Amounts of drug retained in the corneal tissue were also higher for NM. In vitro and in vivo tests showed no signs of irritation or toxicity and successful in vivo anti-inflammatory efficacy for both formulations, being NM-OA/UA NPs the most effective. From the clinical editor: Oleanolic acid (OA) and ursolic acid (UA) are compounds found in plants with anti-inflammatory properties. The authors in this paper designed nanoparticles (NPs) using poly(dl-lactide-coglycolide) acid (PLGA) loaded with these compounds for ophthalmic administration. Both in vitro and in vivo experiments showed no toxicity and significant anti-inflammatory efficacy. This may provide new drugs for ocular anti-inflammatory treatment.
authors: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: Helen L
authors: HL
authors: Alvarado
authors: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: Guadalupe
authors: G
authors: Abrego
authors: Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
authors: María L
authors: ML
authors: Garduño-Ramirez
authors: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain. Electronic address: beatrizclares@ugr.es.
authors: Beatriz
authors: B
authors: Clares
authors: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: Ana C
authors: AC
authors: Calpena
authors: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: María L
authors: ML
authors: García
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005128:Eye Diseases / Q000188:drug therapy; D053758:Nanoparticles / Q000737:chemistry*; D009828:Oleanolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits; D014315:Triterpenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D009828:Oleanolic Acid; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Anti-inflammatory efficacy; Ocular administration; Oleanolic acid; PLGA nanoparticles; Ursolic acid