Lipid-polyethylene glycol based nano-ocular formulation of ketoconazole

Kakkar, Shilpa; Karuppayil, Sankunny Mohan; Raut, Jayant S.; Giansanti, Fabrizio; Papucci, Laura; Schiavone, Nicola; Kaur, Indu Pal

doi:10.1016/j.ijpharm.2015.08.088

Cited by 75 publications

(39 citation statements)

References 81 publications

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“…The bulky and highly hydrated corona of the PEG extending from the lipid bilayer into the aqueous phase is critical for enhancing steric stabilization of the nanoparticles (23). Also, incorporation of PEG could allow better stabilization against aggregation, on storage and on sterilization - by amorphization and inducing imperfections in crystal lipid lattices (24, 25). …”

Section: Introductionmentioning

confidence: 99%

Ocular disposition of ciprofloxacin from topical, PEGylated nanostructured lipid carriers: Effect of molecular weight and density of poly (ethylene) glycol

Balguri

Adelli

Janga

et al. 2017

International Journal of Pharmaceutics

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Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. The objective of the present project is to investigate the effect of surface PEG functionalization of the Nano structured lipid carriers (NLCs) on formulation stability, ocular penetration and distribution. CIP NLCs were tested with different molecular weight (poly ethylene glycol) PEGs ranging from (2K to 20K) grafted onto the phospholipid and with different chain lengths (14–18 carbons) of phospholipids derivatized with PEG-2K. Drug load in the formulations was maintained at 0.3% w/v. Formulations prepared were evaluated with respect to in vitro release, transcorneal permeation, autoclavability, morphological characteristics and in vivo ocular tissue distribution. Scanning Transmission electron microscopy (STEM) studies revealed that the PEG-CIP-NLCs were spherical in shape. Transcorneal penetration of CIP was optimum with PEG molecular weight in between 2K to 10K. Carbon chain length of the phospholipid, however, did not affect transcorneal penetration of CIP. In vivo ocular tissue CIP concentrations attained from the various formulations was consistent with the in vitro data obtained. The results suggest that surface functionalization of PEGs, within a specified range of molecular weight and surface packing density, significantly enhance trans-ocular penetration and impart sterilization-stabilization characteristics into the formulations.

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Section: Introductionmentioning

confidence: 99%

Ocular disposition of ciprofloxacin from topical, PEGylated nanostructured lipid carriers: Effect of molecular weight and density of poly (ethylene) glycol

Balguri

Adelli

Janga

et al. 2017

International Journal of Pharmaceutics

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“…Solid lipid nanoparticles (SLN) ocular dispersion of KET comprising Compritol 888 ATO and PEG 600 matrix were prepared using hot highpressure homogenization (Kakkar et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies

2017

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Context: Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance. Objective: Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis. Materials and methods: The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated. An ex vivo corneal permeation study to determine the level of KET in the external eye tissue of albino rabbits and an in vivo assessment of the level of KET in the aqueous humors were performed. Results and discussion: In vivo evaluation showed an increase in bioavailability up to 20-folds from the optimum KET proniosomal gel formula in the aqueous humor compared to drug suspension (KET-SP). The selected formulae were composed of spans being hydrophobic suggesting the potential use of a more hydrophobic surfactant as Span during the formulation of formulae. Factors that stabilize the vesicle membrane and increase the entrapment efficiency of KET (namely low HLB, long alkyl chain, high phase transition temperature) slowed down the release profile. Conclusions: Proniosomal gels as drug delivery carriers were proven to be a promising approach to increase corneal contact and permeation as well as retention time in the eye resulting in a sustained action and enhanced bioavailability.

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“…Moreover, it is difficult for the drug to present in a solubilized form in the aqueous corneal surface due to the limited aqueous solubility. 5 Ocular drug administration offers lower incidence of systemic drug side effects and drug-drug interactions that are common during systemic treatment. However, due to the unique anatomy and physiology of the eye, ocular drug delivery represents a major challenge during the development of effective ophthalmic preparations.…”

Section: Introductionmentioning

confidence: 99%

“…6 Nanoparticulate drug delivery systems have been reported to deliver the administered drug successfully across the different eye segments, including the posterior part. 5,7 Polymeric nanoparticles (NPs), especially those that have been developed using biocompatible-biodegradable polymers, such as polycaprolactone, poly(alkyl cyanoacrylate) and poly(lactide-coglycolide) (PLGA), are a promising ocular delivery system due to enhanced bioavailability and reduced frequency of administration. 8,9 PLGA-based NPs are the most suitable polymeric nanoparticulate ocular drug delivery owing to ease of fabrication and approval by the FDA for drug delivery.…”

Section: Introductionmentioning

confidence: 99%

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole

Ahmed

Aljaeid²

2017

IJN

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Oral ketoconazole therapy is commonly associated with serious hepatotoxicity. Improving ocular drug delivery could be sufficient to treat eye fungal infections. The purpose of this study was to develop optimized ketoconazole poly(lactide-co-glycolide) nanoparticles (NPs) with subsequent loading into in situ gel (ISG) formulation for ophthalmic drug delivery. Three formulation factors were optimized for their effect on particle size (Y1) and entrapment efficiency (Y2) utilizing central composite experimental design. Interaction among components was studied using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Ketoconazole crystalline state was studied using X-ray powder diffraction. Six different polymeric ISG formulations were prepared and loaded with either optimized NPs or a pure drug. The prepared ISG formulations were characterized for in vitro gelation, drug release and antifungal activity. The permeation through human epithelial cell line was also investigated. The results revealed that all the studied formulation parameters significantly affected Y1 and Y2 of the developed NPs. DSC and FTIR studies illustrated compatibility among NP components, while there was a change from the crystalline state to the amorphous state of the NPs. The in vitro release from the ISG formulations loaded with drug NPs showed sustained and enhanced drug release compared to pure drug formulations. In addition, ISG loaded with NPs showed enhanced anti-fungal activity compared to pure drug formulations. Alginate–chitosan ISG formulation loaded with optimized ketoconazole NPs illustrated higher drug permeation through epithelial cell lines and is considered as an effective ophthalmic drug delivery in the treatment of fungal eye infections.

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Lipid-polyethylene glycol based nano-ocular formulation of ketoconazole

Cited by 75 publications

References 81 publications

Ocular disposition of ciprofloxacin from topical, PEGylated nanostructured lipid carriers: Effect of molecular weight and density of poly (ethylene) glycol

Ocular disposition of ciprofloxacin from topical, PEGylated nanostructured lipid carriers: Effect of molecular weight and density of poly (ethylene) glycol

Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole

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