Dual Drug Loaded Lipid Nanocarrier Formulations for Topical Ocular Applications

Youssef, Ahmed Adel Ali; Dudhipala, Narendar; Majumdar, Soumyajit

doi:10.2147/ijn.s360740

Cited by 22 publications

(17 citation statements)

References 47 publications

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“…Analysis was conducted at 25 °C with an angle of detection of 90°. Zeta potential (ZP) was measured using the same diluted sample for each formulation 21 , 22 . Each value was the average of three measurements.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, IR-SLNs and IR-HPβCD-SLNs showed a small particle size (<300 nm), better polydispersity index (<0. 22), optimum values for zeta potential (-30.0 mV), high % entrapment efficiency (92.4±1.6), and showed sustained release of IR compared to the IR-CD (HPβCD and βCD) inclusion complexes, and IR suspension (IR-CS) over a period of 48 h [18]. The current study aimed to extend our previous investigation to confirm formulation parameters' reproducibility and to evaluate the in vivo pharmacokinetic (PK) and pharmacodynamic (PD) performance of the lead formulations in normotensive and hypertension-induced rats, in comparison with IR-CS as control formulation.…”

Section: Ivyspringmentioning

confidence: 99%

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Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability

Dudhipala¹,

Ettireddy²,

Youssef³

et al. 2023

Nanotheranostics

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Background: Irbesartan (IR) is used in the treatment of hypertension, heart failure, and nephropathy in Type II diabetes. IR bioavailability is limited by poor solubility and presystemic metabolism. In our previous investigations, cyclodextrin (HPβCD) complexed solid lipid nanoparticles (SLNs) of IR were prepared, optimized, and characterized. The current study aimed to confirm the reproducibility of the previous methodology and to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of the selected lead formulations in an experimental animal model. Methods: SLNs were prepared by hot homogenization followed by probe sonication with IR/HPβCD inclusion complex loaded into a solid lipid (Dynasan 112). SLNs were evaluated for physical characteristics, drug content, entrapment efficiency, in vitro release profile, and surface morphology. The pharmacokinetic and pharmacodynamic behavior of the SLNs were evaluated in Wistar rats. Results: Photon correlation spectroscopy, drug content, entrapment efficiency, and dissolution studies results were reproducible and consistent with our earlier investigation. PK studies showed 2.1-, 6.6-, and 9.9-fold improvement in the relative oral bioavailability of the drug from IR-HPβCD, IR-SLN, and IR-HPβCD-SLN formulations, respectively compared to IR suspension. However, IR-HPβCD-SLNs showed 1.5-and 4.7-fold improvement in the relative oral bioavailability of the drug compared to IR-SLN and IR-HPβCD formulations, respectively. PD studies in hypertensive Wistar rats showed a good control over systolic blood pressure for 48 h for SLN formulations compared to 2 h for IR suspension. However, the IR-HPβCD inclusion complex exhibited immediate antihypertensive activity (0.5 h) with a period of systolic blood pressure control similar to IR suspension. Conclusions: The current approach exhibited improved oral bioavailability along with improved and prolonged pharmacodynamic effect.

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Section: Methodsmentioning

confidence: 99%

Section: Ivyspringmentioning

confidence: 99%

Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability

Dudhipala¹,

Ettireddy²,

Youssef³

et al. 2023

Nanotheranostics

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“…Another advantageous characteristic of the lipid nanocarriers is the possibility of encapsulating more than one therapeutic agent, leading to the elaboration of dual or multidrug lipid nanoparticles, characterized by a synergetic effect and improved therapeutic performance [ 118 ]. In ophthalmology, in particular, SLNs and the second-generation lipid particles—NLCs—are considered especially beneficial due to their ability to provide sustained drug release by acting as drug depot formulations, and enhance corneal penetration due to the corresponding activity of non-ionic surfactants included in their structure [ 119 , 120 ]. The latter may further contribute towards an improved ocular bioavailability, by opening the tight junctions between corneal epithelial cells, facilitating paracellular drug transport, and by inhibiting P-glycoprotein activity, limiting drug efflux [ 121 , 122 , 123 ].…”

Section: Feasibility Of Lipid Nanoparticles In Ophthalmologymentioning

confidence: 99%

“…The selection of model drugs (an antifungal agent and fluoroquinolone antibiotic) was based on the complex etiology of corneal infections (which may be caused by bacteria/fungi/protozoa, when a secondary or co-infection is present). The elaborated dual NLCs were subsequently incorporated into in situ ionic gel formulations, aiming to further enhance the therapeutic efficacy by providing prolonged ocular surface contact time [ 120 ]. Dual therapeutic synergy was exploited also by Chen and Wu when developing brinzolamide- and latanoprost-loaded NLCs for the therapy of glaucoma (details of the study are presented in Table 3 ) [ 192 ].…”

Section: Feasibility Of Lipid Nanoparticles In Ophthalmologymentioning

confidence: 99%

Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms

Gugleva

Andonova

2023

Pharmaceuticals

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Sufficient ocular bioavailability is often considered a challenge by the researchers, due to the complex structure of the eye and its protective physiological mechanisms. In addition, the low viscosity of the eye drops and the resulting short ocular residence time further contribute to the observed low drug concentration at the target site. Therefore, various drug delivery platforms are being developed to enhance ocular bioavailability, provide controlled and sustained drug release, reduce the number of applications, and maximize therapy outcomes. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) exhibit all these benefits, in addition to being biocompatible, biodegradable, and susceptible to sterilization and scale-up. Furthermore, their successive surface modification contributes to prolonged ocular residence time (by adding cationic compounds), enhanced penetration, and improved performance. The review highlights the salient characteristics of SLNs and NLCs concerning ocular drug delivery, and updates the research progress in this area.

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“…Bacterial invasion of the cornea can interfere with the pathway of light entering the eye globe and destroy the intact epithelial cells covering the cornea, which could result in irreversible visual impairment if left untreated [3]. The most predominant Gram-positive bacteria isolated in BK are Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus viridans, and Enterococcus spp., whereas the most predominant Gram-negative bacteria include Moraxella lacunata, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, Serratia marcescens, Microbacterium lacunata, and Microbacterium liquefaciens [1,4]. The true burden of BK is not known; however, estimates in the US range from 25,000 to 71,000 cases each year, and worldwide rates may exceed 2.0-3.5 million cases annually [5,6].…”

Section: Introductionmentioning

confidence: 99%

Design of Topical Moxifloxacin Mucoadhesive Nanoemulsion for the Management of Ocular Bacterial Infections

et al. 2022

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Ocular bacterial infections can lead to serious visual disability without proper treatment. Moxifloxacin (MOX) has been approved by the US Food and Drug Administration as a monotherapy for ocular bacterial infections and is available commercially as an ophthalmic solution (0.5% w/v). However, precorneal retention, drainage, and low bioavailability remain the foremost challenges associated with current commercial eyedrops. With this study, we aimed to design a MOX-loaded nanoemulsion (NE; MOX-NE) with mucoadhesive agents (MOX-NEM) to sustain MOX release, as well as to overcome the potential drawbacks of the current commercial ophthalmic formulation. MOX-NE and MOX-NEM formulations were prepared by hot homogenization coupled with probe sonication technique and subsequently characterized. The lead formulations were further evaluated for in vitro release, ex vivo transcorneal permeation, sterilization, and antimicrobial efficacy studies. Commercial MOX ophthalmic solution was used as a control. The lead formulations showed the desired physicochemical properties and viscosity. All lead formulations showed sustained release profiles a period of more than 12 h. Filtered and autoclaved lead formulations were stable for one month (the last time point tested) under refrigeration and at room temperature. Ex vivo transcorneal permeation studies revealed a 2.1-fold improvement in MOX permeation of the lead MOX-NE formulation compared with Vigamox® eyedrops. However, MOX-NEM formulations showed similar flux and permeability coefficients to those of Vigamox® eyedrops. The lead formulations showed similar in vitro antibacterial activity as the commercial eyedrops and crude drug solution. Therefore, MOX-NE and MOX-NEM formulations could serve as effective delivery vehicles for MOX and could improve treatment outcomes in different ocular bacterial infections.

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Dual Drug Loaded Lipid Nanocarrier Formulations for Topical Ocular Applications

Cited by 22 publications

References 47 publications

Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability

Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability

Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms

Design of Topical Moxifloxacin Mucoadhesive Nanoemulsion for the Management of Ocular Bacterial Infections

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