Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: Designs, characterizations, and pharmacokinetics

Siti Norhawani Harun, Syafinaz Amin Nordin, Siti Salwa Abd Gani, Ahmad Fuad Shamsuddin, Mahiran Basri, Hamidon Bin Basri

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood–brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered. Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties. Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of −46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0–t, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0–t, prolonged half-life, and lower clearance as compared to free cefuroxime solution. Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

Original languageEnglish
Pages (from-to)2571-2584
Number of pages14
JournalInternational Journal of Nanomedicine
Volume13
DOIs
Publication statusPublished - 27 Apr 2018

Fingerprint

Cefuroxime
Pharmacokinetics
Brain
Rats
Neurology
Polydispersity
Zeta potential
Drug delivery
Blood
Particle size
Viscosity
Transmission electron microscopy
Plasmas
Molecules
Half-Life
Pharmaceutical Preparations
Central Nervous System Diseases
Transmission Electron Microscopy
Particle Size
Osmolar Concentration

Keywords

  • Blood–brain barrier
  • Cefuroxime
  • Drug delivery
  • Parenteral nanoemulsion
  • Pharmacokinetics

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Drug Discovery
  • Organic Chemistry

Cite this

Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime : Designs, characterizations, and pharmacokinetics. / Harun, Siti Norhawani; Nordin, Syafinaz Amin; Gani, Siti Salwa Abd; Shamsuddin, Ahmad Fuad; Basri, Mahiran; Basri, Hamidon Bin.

In: International Journal of Nanomedicine, Vol. 13, 27.04.2018, p. 2571-2584.

Research output: Contribution to journalArticle

Harun, Siti Norhawani ; Nordin, Syafinaz Amin ; Gani, Siti Salwa Abd ; Shamsuddin, Ahmad Fuad ; Basri, Mahiran ; Basri, Hamidon Bin. / Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime : Designs, characterizations, and pharmacokinetics. In: International Journal of Nanomedicine. 2018 ; Vol. 13. pp. 2571-2584.
@article{3e0788358da4413fbac0b3dc0606c8c3,
title = "Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: Designs, characterizations, and pharmacokinetics",
abstract = "Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood–brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered. Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties. Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of −46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0–t, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0–t, prolonged half-life, and lower clearance as compared to free cefuroxime solution. Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.",
keywords = "Blood–brain barrier, Cefuroxime, Drug delivery, Parenteral nanoemulsion, Pharmacokinetics",
author = "Harun, {Siti Norhawani} and Nordin, {Syafinaz Amin} and Gani, {Siti Salwa Abd} and Shamsuddin, {Ahmad Fuad} and Mahiran Basri and Basri, {Hamidon Bin}",
year = "2018",
month = "4",
day = "27",
doi = "10.2147/IJN.S151788",
language = "English",
volume = "13",
pages = "2571--2584",
journal = "International Journal of Nanomedicine",
issn = "1176-9114",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime

T2 - Designs, characterizations, and pharmacokinetics

AU - Harun, Siti Norhawani

AU - Nordin, Syafinaz Amin

AU - Gani, Siti Salwa Abd

AU - Shamsuddin, Ahmad Fuad

AU - Basri, Mahiran

AU - Basri, Hamidon Bin

PY - 2018/4/27

Y1 - 2018/4/27

N2 - Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood–brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered. Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties. Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of −46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0–t, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0–t, prolonged half-life, and lower clearance as compared to free cefuroxime solution. Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

AB - Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood–brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered. Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties. Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of −46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0–t, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0–t, prolonged half-life, and lower clearance as compared to free cefuroxime solution. Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

KW - Blood–brain barrier

KW - Cefuroxime

KW - Drug delivery

KW - Parenteral nanoemulsion

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=85047944184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047944184&partnerID=8YFLogxK

U2 - 10.2147/IJN.S151788

DO - 10.2147/IJN.S151788

M3 - Article

C2 - 29731632

AN - SCOPUS:85047944184

VL - 13

SP - 2571

EP - 2584

JO - International Journal of Nanomedicine

JF - International Journal of Nanomedicine

SN - 1176-9114

ER -