AI Article Synopsis
- The study developed a novel co-loaded liposomal formulation (CLL) for glaucoma treatment that combines timolol maleate (TM) and acetazolamide (Acz) to improve drug delivery and effectiveness.
- Preliminary experiments assessed the interaction between Acz and HPβCD to enhance solubility, along with screening various formulation factors that impact the product's quality.
- In vitro and in vivo studies indicated that the CLL formulation significantly improved drug release, permeation, and reduced intraocular pressure more effectively than formulations with single drugs, showcasing the benefits of combining the active ingredients and drug delivery systems.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709067 | PMC |
| http://dx.doi.org/10.3390/pharmaceutics13122010 | DOI Listing |
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