Development and Optimization of Methotrexate-Loaded Lipid-Polymer Hybrid Nanoparticles for Controlled Drug Delivery Applications

Nayab Tahir, Asadullah Madni, Vimalkumar Balasubramanian, Mubashar Rehman, Alexandra Maria Rebelo Correia, Prince Muhammad Kashif, Ermei Mäkilä, Jarno Salonen, Helder Almeida Santos

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert® software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176−308 nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34-91.95% and the release mechanism follow the Higuchi model (R2=0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes.
Original languageEnglish
JournalInternational Journal of Pharmaceutics
Volume533
Issue number1
Pages (from-to)156–168
Number of pages13
ISSN0378-5173
DOIs
Publication statusPublished - 25 Nov 2017
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy
  • Lipid-polymer hybrid
  • Nanoparticles
  • Box Behnken
  • Methotrexate
  • Drug delivery
  • BOX-BEHNKEN DESIGN
  • POROUS SILICON NANOPARTICLES
  • BREAST-CANCER-TREATMEN T
  • IN-VITRO EVALUATION
  • COMBINATION THERAPY
  • ANTITUMOR-ACTIVITY
  • CONTROLLED-RELEASE
  • HYDROPHOBIC DRUGS
  • CELLULAR UPTAKE
  • ORAL DELIVERY

Cite this

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title = "Development and Optimization of Methotrexate-Loaded Lipid-Polymer Hybrid Nanoparticles for Controlled Drug Delivery Applications",
abstract = "Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert{\circledR} software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176−308 nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34-91.95{\%} and the release mechanism follow the Higuchi model (R2=0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes.",
keywords = "317 Pharmacy, Lipid-polymer hybrid , Nanoparticles , Box Behnken , Methotrexate , Drug delivery , BOX-BEHNKEN DESIGN , POROUS SILICON NANOPARTICLES , BREAST-CANCER-TREATMEN T, IN-VITRO EVALUATION , COMBINATION THERAPY , ANTITUMOR-ACTIVITY , CONTROLLED-RELEASE , HYDROPHOBIC DRUGS , CELLULAR UPTAKE , ORAL DELIVERY",
author = "Nayab Tahir and Asadullah Madni and Vimalkumar Balasubramanian and Mubashar Rehman and {Rebelo Correia}, {Alexandra Maria} and {Muhammad Kashif}, Prince and Ermei M{\"a}kil{\"a} and Jarno Salonen and {Almeida Santos}, Helder",
year = "2017",
month = "11",
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language = "English",
volume = "533",
pages = "156–168",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier Scientific Publ. Co",
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Development and Optimization of Methotrexate-Loaded Lipid-Polymer Hybrid Nanoparticles for Controlled Drug Delivery Applications. / Tahir, Nayab ; Madni, Asadullah ; Balasubramanian, Vimalkumar; Rehman, Mubashar ; Rebelo Correia, Alexandra Maria; Muhammad Kashif, Prince ; Mäkilä, Ermei; Salonen, Jarno; Almeida Santos, Helder.

In: International Journal of Pharmaceutics, Vol. 533, No. 1, 25.11.2017, p. 156–168.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Development and Optimization of Methotrexate-Loaded Lipid-Polymer Hybrid Nanoparticles for Controlled Drug Delivery Applications

AU - Tahir, Nayab

AU - Madni, Asadullah

AU - Balasubramanian, Vimalkumar

AU - Rehman, Mubashar

AU - Rebelo Correia, Alexandra Maria

AU - Muhammad Kashif, Prince

AU - Mäkilä, Ermei

AU - Salonen, Jarno

AU - Almeida Santos, Helder

PY - 2017/11/25

Y1 - 2017/11/25

N2 - Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert® software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176−308 nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34-91.95% and the release mechanism follow the Higuchi model (R2=0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes.

AB - Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert® software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176−308 nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34-91.95% and the release mechanism follow the Higuchi model (R2=0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes.

KW - 317 Pharmacy

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KW - BOX-BEHNKEN DESIGN

KW - POROUS SILICON NANOPARTICLES

KW - BREAST-CANCER-TREATMEN T

KW - IN-VITRO EVALUATION

KW - COMBINATION THERAPY

KW - ANTITUMOR-ACTIVITY

KW - CONTROLLED-RELEASE

KW - HYDROPHOBIC DRUGS

KW - CELLULAR UPTAKE

KW - ORAL DELIVERY

UR - https://www.journals.elsevier.com/international-journal-of-pharmaceutics/

U2 - 10.1016/j.ijpharm.2017.09.061

DO - 10.1016/j.ijpharm.2017.09.061

M3 - Article

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EP - 168

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

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