Abstract

Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood–brain barrier. Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells. Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential −16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.

Original languageEnglish
Pages (from-to)2144-2153
Number of pages10
JournalDrug Delivery
Volume23
Issue number7
DOIs
Publication statusPublished - 01-09-2016

Fingerprint

Carboplatin
Nanoparticles
Nose
Intranasal Administration
Brain
polycaprolactone
Particle Size
Perfusion
Drug Compounding
Nasal Mucosa
Differential Scanning Calorimetry
Glioblastoma
Emulsions
Glioma
Electron Scanning Microscopy
Wistar Rats
Sheep
Polymers

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

@article{ecbbfdfddbeb4a5bbc7a01f2db3e0c70,
title = "Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery",
abstract = "Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood–brain barrier. Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells. Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential −16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.",
author = "Alex, {Angel Treasa} and Alex Joseph and Gopal Shavi and Rao, {Josyula Venkata} and Nayanabhirama Udupa",
year = "2016",
month = "9",
day = "1",
doi = "10.3109/10717544.2014.948643",
language = "English",
volume = "23",
pages = "2144--2153",
journal = "Drug Delivery",
issn = "1071-7544",
publisher = "Informa Healthcare",
number = "7",

}

Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery. / Alex, Angel Treasa; Joseph, Alex; Shavi, Gopal; Rao, Josyula Venkata; Udupa, Nayanabhirama.

In: Drug Delivery, Vol. 23, No. 7, 01.09.2016, p. 2144-2153.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery

AU - Alex, Angel Treasa

AU - Joseph, Alex

AU - Shavi, Gopal

AU - Rao, Josyula Venkata

AU - Udupa, Nayanabhirama

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood–brain barrier. Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells. Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential −16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.

AB - Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood–brain barrier. Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells. Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential −16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.

UR - http://www.scopus.com/inward/record.url?scp=84991573823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991573823&partnerID=8YFLogxK

U2 - 10.3109/10717544.2014.948643

DO - 10.3109/10717544.2014.948643

M3 - Article

C2 - 25544603

AN - SCOPUS:84991573823

VL - 23

SP - 2144

EP - 2153

JO - Drug Delivery

JF - Drug Delivery

SN - 1071-7544

IS - 7

ER -