Evidence map›Paper›PMID 34959292›Full record

ArticlePharmaceutics2021

Synergistic Effect of Acetazolamide-(2-hydroxy)propyl β-Cyclodextrin in Timolol Liposomes for Decreasing and Prolonging Intraocular Pressure Levels.

Carmen M Arroyo-García, Daniela Quinteros, Santiago D Palma, Cesáreo J Jiménez de Los Santos, José R Moyano, Antonio M Rabasco, María Luisa González-Rodríguez

Abstract read
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Recent advances and future challenges in nanosystems for ocular drug delivery.The Journal of pharmacology and experimental therapeutics · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Carmen M Arroyo-GarcíaDepartment of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, C/Prof. García González, 2, 41012 Sevilla, Spain.
Daniela QuinterosUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000, Argentina.
Santiago D PalmaUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000, Argentina.
Cesáreo J Jiménez de Los SantosDepartment of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, C/Prof. García González, 2, 41012 Sevilla, Spain.
José R MoyanoDepartment of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, C/Prof. García González, 2, 41012 Sevilla, Spain.
Antonio M RabascoDepartment of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, C/Prof. García González, 2, 41012 Sevilla, Spain.ORCID 0000-0002-8861-6090
María Luisa González-RodríguezDepartment of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, C/Prof. García González, 2, 41012 Sevilla, Spain.ORCID 0000-0002-2450-1622

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl β-cyclodextrin (HPβCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. A preliminary study comprising the Acz/HPβCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion complexation behavior, characterization, and binding ability of Acz with HPβCD showed that HPβCD could enhance the water solubility of Acz despite the weak binding ability of the complex. Ch disturbed the stability and solubility parameters of Acz due to the fact of its competence by CD; thus, Chems (steroid derivative) was selected for further liposome formulation studies. The optimization of the lipid bilayer composition (DDAB, 0.0173 mmol and no double loading) and the extrusion as methods to reduce vesicle size were crucial for improving the physico-chemical properties and encapsulation efficiency of both drugs. In vitro release and permeation studies demonstrated that the CLL formulation showed improvement in in vitro drug release and permeation compared to the liposomal formulations with a single drug (TM-L and AczHP-L) and the standard solutions (TM-S and AczHP-S). CLL showed high efficacy in reducing and prolonging IOP, suggesting that the synergistic effect of TM and Acz on aqueous humor retention and the presence of this cyclodextrin and liposomes as permeation enhancers are responsible for the success of this strategy of co-loading for glaucoma therapy.

Indexed as

(2-hydroxy)propyl β-cyclodextrin31PNMRacetazolamideco-loadingcyclodextrin competencedesign of experimentsdrug deliveryglaucomaintraocular pressureliposometimolol

Identifiers

PMID34959292
PMCPMC8709067

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.