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Clozapine-laden carbon dots delivered to the brain via an intranasal pathway: Synthesis, characterization, ex vivo, and in vivo studies.
Patel, Hetal P; Desai, Priya H; Patel, Rikin V; Lodha, Sandesh N; Gore, Anil H; Patil, Pravin O; Desai, Bhargavi V; Desai, Ditixa T; Vyas, Bhavin A; Willcox, Mark D P; Maulvi, Furqan A.
Afiliación
  • Patel HP; Department of Pharmaceutics, Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India. Electronic address: hetalppatel1986@gmail.com.
  • Desai PH; Department of Pharmaceutics, Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
  • Patel RV; Intas Pharmaceutical Ltd., Ahmedabad 380054, India.
  • Lodha SN; Department of Pharmaceutics, Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
  • Gore AH; Tarsadia Institute of Chemical Science, Uka Tarsadia University, Maliba Campus, Surat 394350, India.
  • Patil PO; Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, India.
  • Desai BV; Department of Pharmaceutics, Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
  • Desai DT; Department of Pharmaceutics, Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
  • Vyas BA; Department of Pharmaceutics, Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
  • Willcox MDP; School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Maulvi FA; Department of Pharmaceutics, Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India; School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales 2052, Australia. Electronic address: f.maulvi@unsw.edu.au.
Colloids Surf B Biointerfaces ; 237: 113862, 2024 May.
Article en En | MEDLINE | ID: mdl-38518556
ABSTRACT
Clozapine, which is widely used to treat schizophrenia, shows low bioavailability due to poor solubility and high first-pass metabolism. The study aimed to design clozapine-loaded carbon dots (CDs) to enhance availability of the clozapine to the brain via intranasal pathway. The CDs were synthesized by pyrolysis of citric acid and urea at 200 °C by hydrothermal technique and characterized by photoluminescence, transmission electron microscopy (TEM), X-ray Photoelectron Spectrometer (XPS), and Fourier transform infrared spectrum (FTIR). The optimized clozapine-loaded CDs (CLZ-CDs-13-200) showed a quasi-spherical shape (9-12 nm) with stable blue fluorescence. The CDs showed high drug solubilization capacity (1.5 mg drug in 1 mg/ml CDs) with strong electrostatic interaction with clozapine (drug loading efficiency = 94.74%). The ex vivo release study performed using nasal goat mucosa showed sustained release of clozapine (43.89%) from CLZ-CDs-13-200 for 30 h. The ciliotoxicity study (histopathology) confirmed no toxicity to the nasal mucosal tissues using CDs. In the rat model (in vivo pharmacokinetic study), when CDs were administrated by the intranasal route, a significantly higher concentration of clozapine in the brain tissue (Cmax = 58.07 ± 5.36 µg/g and AUCt (µg/h*g) = 105.76 ± 12.31) was noted within a short time (tmax = 1 h) compared to clozapine suspension administered by intravenous route (Cmax = 20.99 ± 3.91 µg/g, AUC t (µg/h*g) = 56.89 ± 12.31, and tmax = 4 h). The high value of drug targeting efficiency (DTE, 486%) index and direct transport percentage (DTP, 58%) indicates the direct entry of clozapine-CDs in the brain via the olfactory route. In conclusion, designed CDs demonstrated a promising dosage form for targeted nose-to-brain delivery of clozapine for the effective treatment of schizophrenia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clozapina / Puntos Cuánticos Límite: Animals Idioma: En Revista: Colloids Surf B Biointerfaces Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clozapina / Puntos Cuánticos Límite: Animals Idioma: En Revista: Colloids Surf B Biointerfaces Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos