Development and Investigation of Timolol Maleate and Latanoprost Combination Liposomes for the Treatment of Glaucoma

Dubey, Akhilesh; Prabhu, Prabhakara; Beladiya, Ketan; Nair, Nitin; Ghate, Vivek

doi:10.7897/2230-8407.06457

Cited by 8 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was also found that the release kinetics for both drugs follow a zero-order model. Animal studies also showed that the liposomal formulation of Timolol/latanoprost compared with the marketing formulation of Timolol/latanoprost reduces IOP equally after four days, and before that, the pressure reduction slope was in favor of the commercial formulation [57]. Our study had a longer release (12h VS 6h), lower EE%, and different release kinetics for Timolol ( rst-order VS zero-order) compared to this study.…”

Section: Discussionmentioning

confidence: 40%

Cationic liposomes as promising vehicles forTimolol/Brimonidine combination ocular delivery in glaucoma: Formulation development and in vitro/in vivo evaluation

Makhmalzadeh

Feghhi

2022

Preprint

View full text Add to dashboard Cite

Glaucoma is a chronic eye disease in which the pressure inside the eye increases and leads to damage to the optic nerve, and eventually causes blindness. In this disease, it is often necessary to use a multi-drug treatment system. There is a xed combination of Timolol maleate and Brimonidine tartrate among the combination drugs in glaucoma treatment. Liposomes are one of the most important targeted drug delivery systems to eye tissue, which leads to improved drug permeability and durability in ocular tissue.In this study, Thin Layer Hydration was used to make liposomal formulations containing Timolol maleate (TM) and Brimonidine tartrate (BT). After the necessary evaluations, one of the eight initial formulations was selected as an optimization formulation. Then, characteristics such as drug loading percentage, particle size, pH, zeta potential, and drug release were performed on the optimized formulation. The study of reducing intraocular pressure was performed on the optimized formulation.This study in total was performed on 18Rabbits in three groups. Hydroxypropyl methylcellulose (HPMC) polymer was injected into the anterior chamber to Experimental induce glaucoma.The selected formulation was within the acceptable range of ocular products in terms of physical properties. HPMC polymer injection successfully induced glaucoma in the animal model, resulting in a 79% increase in intraocular pressure. The results showed that the liposomal formulation signi cantly reduced the intraocular pressure compared to the simple formulation of the aqueous solution, and both formulations were able to signi cantly reduce the intraocular pressure compared to the control group(p < 0.001). The results also showed that liposomal formulation hasa therapeutic effect in reducing intraocular pressure and has a preventive effect and intraocular pressure return to normal value after 90 h. It seems that selected liposomal formulation made by Thin Layer Hydration can act as a suitable drug carrier to increase the effectiveness of the xed combination of Timolol maleate and Brimonidine tartrate and be proposed as a new drug formulation for targeted and controlled drug delivery in the treatment of glaucoma.

show abstract

Section: Discussionmentioning

confidence: 40%

Cationic liposomes as promising vehicles forTimolol/Brimonidine combination ocular delivery in glaucoma: Formulation development and in vitro/in vivo evaluation

Makhmalzadeh

Feghhi

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…pH of the formulations was measured using digital pH meter. [25] Density (wt/ml) of the liposomal formulations was determined using pycnometer.…”

Section: Physical Appearance Ph and Densitymentioning

confidence: 99%

Untitled

Janbandhu¹

2018

AJP

View full text Add to dashboard Cite

Aims: The aim of the study deals with the design, development, and comparative stability studies of optimized formulations as well as potential formula and process optimization trials of novel orlistat liposomal dispersion. All the experimental studies were evaluated for stability study profiles with respect to physical and chemical key parameters such as physical appearance, pH, density, drug entrapment efficiency, drug content, particle size, polydispersity index and zeta potential. The stability study was carried out at different temperature storage conditions. Materials and Methods: Formula optimization studies were utilized to investigate the impact of different molar ratios of orlistat, soya phosphatidylcholine, and cholesterol. Process optimization studies were also performed to comprehend the effect of variable stirring time, sonication time, and centrifugation time on the physical and chemical factors. Orlistat liposomal formulations were prepared using ethanol injection method. Results and Discussion: Percentage entrapment efficiency of F30 and F31 has 90.6 ± 0.3% and 89.0 ± 0.2% and average particle size of 847.9 nm and 848.1 nm, respectively, and rest of the physical and chemical parameters were satisfactory. Conclusions: The basic aim of the study was achieved with maximum % entrapment efficiency with smaller particle size. The optimized formulations have satisfactory physicochemical parameters at the initial time point and retained similar during stability at long-term storage conditions up to 6 months. Optimized formulations were stable up to 1 month at accelerated storage condition, but there was a significant change observed at 2 and 3 months.

show abstract

“…In the ophthalmic field, fewer studies have been realized with liposomes. Dubey et al [11] developed a latanoprost-timolol maleate fixed combination in liposomes, having the advantage of a more convenient delivery system as well as providing a simple summing effect of the two constituents. Fahmy et al [12] demonstrated the effectiveness of liposomal carriers of latanoprost and thymoquinone in lowering the IOP upon subconjunctival injection, extending the study to evaluate the effect on the aqueous humor oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Development and Investigation of Timolol Maleate and Latanoprost Combination Liposomes for the Treatment of Glaucoma

Cited by 8 publications

References 15 publications

Cationic liposomes as promising vehicles forTimolol/Brimonidine combination ocular delivery in glaucoma: Formulation development and in vitro/in vivo evaluation

Cationic liposomes as promising vehicles forTimolol/Brimonidine combination ocular delivery in glaucoma: Formulation development and in vitro/in vivo evaluation

Untitled

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

Contact Info

Product

Resources

About