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. 2022 Jun 25:17:2753-2776.
doi: 10.2147/IJN.S370192. eCollection 2022.

Augmented in vitro and in vivo Profiles of Brimonidine Tartrate Using Gelatinized-Core Liposomes

Engy A Abdel Azim  1 , Seham A Elkheshen #  2 , Rania M Hathout #  3 , Marwa A Fouly  4 , Nada M El Hoffy  1
Affiliations

Augmented in vitro and in vivo Profiles of Brimonidine Tartrate Using Gelatinized-Core Liposomes

Engy A Abdel Azim et al. Int J Nanomedicine. .

Abstract

Background: The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized core liposomes (GCLs) were fabricated to increase the drug entrapment, corneal penetration, and physical stability of the investigated molecule.

Research design and methods: GCLs encapsulating BRT were prepared and optimized utilizing D-optimal design (DOD). The effect of plasticizer incorporation on the physicochemical characteristics and on the in vivo performance was studied. The optimized formulations were investigated for pH, rheological properties, morphological characteristics, in vitro release profiles, biological performance, safety profile. The effects of storage and gamma sterilization were also investigated.

Results: The results revealed the great success of the prepared formulations to achieve high entrapment efficiency reaching 98% after a maturation period of 10 days. The addition of glycerol as plasticizer significantly minimized the particle size and shortened the maturation period to 7 days. The selected formulations were stable for 3 months after gamma sterilization. The formulations showed significant lowering of intra-ocular pressure (IOP) in glaucomatous rabbits with sustainment of the pharmacological effect for 24 hours compared to drug solution.

Conclusions: Enhanced in vitro and in vivo profiles of brimonidine tartrate loaded gelatinized-core-liposomes were obtained.

Keywords: BRT; D-optimal design; DOD; IOP; brimonidine tartrate; gelatin; gelatinized core liposomes; glaucoma; intra-ocular pressure; ocular drug delivery; plasticizer.

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Conflict of interest statement

The authors declare no conflicts of interest in relation to this work.

Figures

Figure 1
Figure 1
Example of 3D response surface plot for the effect of formulation factors on the particle size of the prepared formulations, The Box Cox plot for the particle size model and the location of the selected formulations in the particle size model (for further evaluation): (A) 3D plot of GL1 through GL12, (B) 3D plot of GLG1 through GLG12, (C) Box Cox plot of GL1 through GL12, (D) Box Cox plot of GLG1 through GLG12 and (E) PS location of the selected formulations.
Figure 2
Figure 2
Transmission electron micrograph (TEM) of the selected formulations, (A) GLG1, (B) GLG4 and (C) GL12.
Figure 3
Figure 3
DSC thermogram of pure components namely; BRT, cholesterol, phosphatidylcholine and gelatin, their physical mixture and the lyophilized formulation; GLG1, GLG4 and GL12.
Figure 4
Figure 4
FTIR spectrums of pure BRT, cholesterol, phosphatidylcholine, gelatin, their physical mixture and the selected formulations; GLG1, GLG4 and GL12.
Figure 5
Figure 5
Percentage of BRT released from the selected GCLs; GLG1, GLG4 and GL12, versus the percentage diffused from drug solutions; 1, 2 and 3, each containing 10 mg of the drug and the equivalent amount of gelatin content of GLG1, GLG2 and GL12, respectively.
Figure 6
Figure 6
IOP lowering over 24 hours for the selected formulations compared to drug solution in isotonic buffer (DS) and control eye (C).
Figure 7
Figure 7
Histological examination of the rabbits’ eye-tissues after one week of treatment with the selected formulation and the drug solution; the control eye (untreated tissue), treated group with GLG1, treated group with GLG4, treated group with GL12 and treated group with drug solution (magnification is 10×).
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