Nanovector approach for co-delivery of Alectinib and Hesperidin via inhalational for lung cancer treatment: development, characterization, and preclinical studies.

Saeem Ahmad, Shahnaj Bano, Nasr A Emad, Shadab Alam, Anjali Rathee, Iqra Zai, Jayamanti Pandit, Mohd Aqil, Yasmin Sultana
Author Information
  1. Saeem Ahmad: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India.
  2. Shahnaj Bano: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India.
  3. Nasr A Emad: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India.
  4. Shadab Alam: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India.
  5. Anjali Rathee: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India.
  6. Iqra Zai: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India.
  7. Jayamanti Pandit: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India.
  8. Mohd Aqil: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India. ORCID
  9. Yasmin Sultana: Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), New Delhi, India. ORCID

Abstract

BACKGROUND: The current study aims to fabricate Nanostructured Lipid Carriers for the co-delivery of Alectinib and Hesperidin (ALB-HSD NLC) for non-small cell lung Cancer (NSCLC) via an inhalational route.
RESEARCH DESIGN AND METHOD: The ALB-HSD NLC was fabricated using Melt emulsification followed by the sonication method and optimized using a central composite design. The optimized formulation was evaluated for various in vitro and studies.
RESULTS: The optimized ALB-HSD NLC had satisfactory results for particle size, Zeta Potential, PDI, and entrapment efficiency. The drug release was more than 2.5-fold higher compared to drugs suspension over 72 hr. A549 human lung cell line study shows IC for ALB and HSD, were 2.289 µg/mL and 73.52 µg/mL, and the dose-dependent toxicity was 0.0209 μg/mL and 0.5213 μg/mL for ALB-HSD NLC formulation and ALB HSD Suspension, respectively, after 72 hr. The Pharmacokinetic study has demonstrated improved AUC0-t (1.38, 1.57-fold) of ALB and HSD from NLC compared to drug suspension. studies give significant results on the syngeneic model.
CONCLUSIONS: The prepared ALB-HSD NLC could be promising drug carriers, and they succeeded in delivering small and efficient doses of ALB and HSD to treat NSCLC.

Keywords

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Created with Highcharts 10.0.0NLCALB-HSDcelllungALBHSDstudyAlectinibHesperidininhalationaloptimizedstudiesdrugcancerco-deliveryNSCLCviausingformulationresults2comparedsuspension72 hrA549 humanline01BACKGROUND:currentaimsfabricateNanostructuredLipidCarriersnon-smallCancerrouteRESEARCHDESIGNANDMETHOD:fabricatedMeltemulsificationfollowedsonicationmethodcentralcompositedesignevaluatedvariousvitroRESULTS:satisfactoryparticlesizeZetaPotentialPDIentrapmentefficiencyrelease5-foldhigherdrugsshowsIC289 µg/mL7352 µg/mLdose-dependenttoxicity0209 μg/mL5213 μg/mLSuspensionrespectivelyPharmacokineticdemonstratedimprovedAUC0-t3857-foldgivesignificantsyngeneicmodelCONCLUSIONS:preparedpromisingcarrierssucceededdeliveringsmallefficientdosestreatNanovectorapproachtreatment:developmentcharacterizationpreclinicallinesC57bl/6miceLLCLung

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