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1.
Int J Pharm ; 656: 124118, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38615806

ABSTRACT

Fungal infections of cornea are important causes of blindness especially in developing nations with tropical climate. However, the challenges associated with current treatments are responsible for poor outcome. Natamycin is the only FDA-approved antifungal drug to treat fungal keratitis, but unfortunately due to its poor water solubility, it is available as suspension. The marketed suspension (5% Natamycin) has rapid precorneal clearance, poor corneal permeability, a higher frequency of administration, and corneal irritation due to undissolved suspended drug particles. In our study, we developed clear and stable natamycin-loaded nanomicelles (1% Natcel) to overcome the above challenges. We demonstrated that 1% Natcel could permeate the cornea better than 5% suspension. The developed 1% Natcel was able to provide sustained release for up to 24 h. Further, it was found to be biocompatible and also improved the mean residence time (MRT) than 5% suspension in tears. Therefore, the developed 1% Natcel could be a potential alternative treatment for fungal keratitis.


Subject(s)
Antifungal Agents , Cornea , Drug Liberation , Eye Infections, Fungal , Keratitis , Micelles , Nanoparticles , Natamycin , Natamycin/administration & dosage , Antifungal Agents/administration & dosage , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Keratitis/drug therapy , Keratitis/microbiology , Animals , Cornea/microbiology , Cornea/metabolism , Cornea/drug effects , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Rabbits , Solubility , Delayed-Action Preparations , Tears/metabolism
2.
Drug Dev Ind Pharm ; 45(5): 826-838, 2019 May.
Article in English | MEDLINE | ID: mdl-30764674

ABSTRACT

OBJECTIVE: The aim of this study was to formulate nanostructured lipid carriers (NLCs) of dithranol-loaded in gel for ease of application and to evaluate its anti-psoriatic efficacy vis-a-vis conventional ointment formulation. SIGNIFICANCE: This study will provide an insight about the use of nanocarriers, esp. NLCs loaded with dithranol for the effective treatment of psoriasis. METHODS: Dithranol-loaded NLCs were prepared by hot melt homogenization method and characterized for particle size and percentage entrapment efficiency. The optimized NLCs were loaded into gel and evaluated for drug release, spreadability, rheological behavior, and staining. Anti-psoriatic efficacy of the NLC gel was evaluated in imiquimod (IMQ) induced psoriatic plaque model in comparison with prepared conventional ointment formulation (1.15% w/w dithranol). RESULTS: NLCs were prepared with particle size below 300 nm, polydispersity index (PDI) below 0.3 and percentage entrapment efficiency of ∼100%. The prepared NLC gel was then compared with the ointment for drug release, staining property, and efficacy. Topical application of dithranol-loaded NLC gel on IMQ-induced psoriatic plaque model reduced the symptoms of psoriasis assessed by both Psoriasis area severity index (PASI) scoring and enzyme-linked immunosorbent assay. There was a significant reduction in disease severity and cytokines like Interleukins-17, 22, 23 and Tumor necrosis factor-α by the developed system in comparison to the negative control. CONCLUSIONS: To conclude dithranol-loaded NLCs in gel base was efficacious in management of psoriasis at the same drug concentration and also offer less cloth staining to that of the ointment product.


Subject(s)
Anthralin/administration & dosage , Dermatologic Agents/administration & dosage , Drug Carriers/chemistry , Psoriasis/drug therapy , Administration, Cutaneous , Animals , Anthralin/pharmacokinetics , Dermatologic Agents/pharmacokinetics , Disease Models, Animal , Drug Liberation , Gels , Humans , Imiquimod/administration & dosage , Imiquimod/immunology , Lipids/chemistry , Male , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Ointments , Particle Size , Psoriasis/diagnosis , Psoriasis/immunology , Psoriasis/pathology , Severity of Illness Index , Skin/drug effects , Skin/pathology , Treatment Outcome
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