Novel thermosensitive poly (N-isopropylacrylamide-covinylpyrrolidone-co-methacrylic acid) nanosystems for delivery of natural products
Keywords:
N-isopropylacrylamide, Thermosensitive, Nanoparticles, Farnesiferol C, Amphiphilic polymersAbstract
The purpose of this research was to synthesize polymer based smart nanosystems for delivery of important bioactive natural products such as sesquiterpene coumarin derivatives of ferula szowitsiana, farnesiferol C as a potent anticancer. To this aim, polymeric micelles were prepared using Nisopropylacrylamide (NIPAAM), vinyl pyrrolidone (VP) and methacrylate (MAA) as monomers which were cross-linked with N, N-methylene bisacrylamide (MBA). The molar ratio of the PNIPAAm: VP: MAA group was 75.7:9.5:14.8. These micelles were further characterized upon their physicochemical properties using particle size analyzer, FT-IR, H-/C-NMR, HPLC. Particle size analyzer resulted in ~500 nm micelles with ~95% drug entrapments. Drug release from the polymeric micelles after 300 hours at 37°C and 40°C were 60 and 98 %, respectively. Upon these findings, it is proposed that the P (N-isopropylacrylamide-co-Methacrylic acid-coVinylpyrrolidone) micelles may be considered as thermosensitive delivery nanosystem.
References
Iranshahi M, Arfa P, Ramezani M, Jaafari MR,
Sadeghian H, Bassarello C, Piacente S, Pizza C.
Sesquiterpene coumarins from Ferula szowitsiana
and in vitro antileishmanial activity of 7-
prenyloxycoumarins against promastigotes., 2007;
:554-561.
Reiner Z, Tedeschi-Reiner E. The effects of plant
sterols on hypercholesterolemia. Lijecnicki
Vjesnik, 2007; 129:276-281.
Iranshahi M, Kalategi F, Rezaee R, Shahverdi
AR, Ito C, Furukawa H, Tokuda H, Itoigawa M.
Cancer chemopreventive activity of terpenoid
coumarins from Ferula species. Planta Medica,
; 74:147-150.
Soga O, Van Nostrum CF, Fens M, Rijcken CJF,
Schiffelers RM, Storm G, Hennink WE.
Thermosensitive and biodegradable polymeric
micelles for paclitaxel delivery. J Controll Rel,
; 103:341-353.
Cheng C, Wei H, Shi BX, Cheng H, Li C, Gu
ZW, Cheng SX, Zhang XZ, Zhuo RX.
Biotinylated thermoresponsive micelle selfassembled from double-hydrophilic block
copolymer for drug delivery and tumor target.
Biomaterials, 2008; 29:497-505.
Wei H, Zhang X, Cheng C, Cheng SX, Zhuo RX.
Self-assembled, thermosensitive micelles of a star
block copolymer based on PMMA and PNIPAAm
for controlled drug delivery. Biomaterials, 2007;
:99-107.
Chung JE, Yamato M, Yokoyama M, Aoyagi T,
Sakurai Y, Okano T. Thermo-responsive drug
delivery of polymeric micelles incorporating
adriamycin. Proceedings of the Controlled
Release Society, 1998; 380-381.
Calvo P, nchez A, nez J, pez MI, Calonge M,
Pastor JC, Alonso MJ. Polyester nanocapsules as
new topical ocular delivery systems for
cyclosporin A. Pharma Res, 1996; 13:311-315.
Calvo P, Vila-Jato JL, Alonso MJ. Comparative in
vitro evaluation of several colloidal systems,
nanoparticles, nanocapsules, and nanoemulsions,
as ocular drug carriers. J Pharma Sci, 1996;
:530-536.
Choi C, Chae SY, Nah JW. Thermosensitive
poly(N-isopropylacrylamide)-b-poly(e-caprolacto
ne) nanoparticles for efficient drug delivery
system. Polymer, 2006; 47:4571-4580.
Hu Y, Zhang L, Cao Y, Ge H, Jiang X, Yang C.
Degradation behavior of poly(epsiloncaprolactone)-b-poly(ethylene glycol)-bpoly(epsilon-caprolactone) micelles in aqueous
solution. Biomacromol, 2004; 5:1756-1762.
Kim SY, Lee YM, Kang JS. Indomethacin-loaded
methoxy poly(ethylene glycol)/poly(D,L-lactide)
amphiphilic diblock copolymeric nanospheres:
Pharmacokinetic and toxicity studies in rodents. J
Biomed Mater Res - Part A, 2005; 74:581-590.
Mainardes RM, Evangelista RC. PLGA
nanoparticles containing praziquantel: Effect of
formulation variables on size distribution. Int J
Pharm, 2005; 290:137-144.
Panyam J, William D, Dash A, Leslie-Pelecky D,
Labhasetwar V. Solid-state solubility influences
encapsulation and release of hydrophobic drugs
from PLGA/PLA nanoparticles. J Pharm Sci,
; 93:1804-1814.
Shenoy D, Little S, Langer R, Amiji M.
Poly(ethylene oxide)-modified poly(?-Amino
Ester) nanoparticles as a pH-sensitive system for
tumor-targeted delivery of hydrophobic drugs:
Part 2. In vivo distribution and tumor localization
studies. Pharma Res, 2005; 22:2107-2114.
Salehi R, Davaran R, Rashidi HR, Entezami A.
Thermosensitive nanoparticles prepared from
poly(N-isopropylacrylamide-acrylamide-vinilpyr
rolidone) and its blend with poly(lactide-coglycolide) for efficient drug delivery system. J
App Poly Sci, 2009; 111:1905-1910.
Salehi R, Arsalani N, Davaran S, Entezami AA.
Synthesis and characterization of thermosensitive
and pH-sensitive poly (N-isopropylacrylamideacrylamide-vinylpyrrolidone) for use in controlled
release of naltrexone. J Biomed Mater Res Part A,
; 9999:NA.
Neradovic D, Soga O, Van Nostrum CF, Hennink
WE. The effect of the processing and formulation
parameters on the size of nanoparticles based on
block copolymers of poly(ethylene glycol) and
poly(N-isopropylacrylamide) with and without
hydrolytically sensitive groups. Biomaterials,
; 25:2409-2418.
Uchida K, Sakai K, Ito E, Hyeong Kwon O,
Kikuchi A, Yamato M, Okano T. Temperaturedependent modulation of blood platelet movement
and morphology on poly(N-isopropylacrylamide)-
grafted surfaces. Biomaterials, 2000; 21:923-929.
Dehghan G, Shafiee A, Ghahremani MH,
Ardestani SK, Abdollahi M. Antioxidant potential
of various extracts from Ferula szovitsiana in
relation to their phenolic content. Pharm Biol,
; 45:691-699.
Dehghan G, Solaimanian R, Shahverdi AR, Amin
G, Abdollahi M, Shafiee A. Chemical
composition and antimicrobial activity of essential
oil of Ferula szovitsiana D.C. Flavour and
Fragrance Journal, 2007; 22:224-227.
Shahverdi AR, Fakhimi A, Zarrini G, Dehghan G,
Iranshahi M. Galbanic acid from Ferula
szowitsiana enhanced the antibacterial activity of
penicillin G and cephalexin against
Staphylococcus aureus. Biol Pharm Bull, 2007;
:1805-1807.
Yin W, Akala EO, Taylor RE. Design of
naltrexone-loaded hydrolyzable crosslinked
nanoparticles. Int J Pharm, 2002; 244:9-19.
Barar J, Javadzadeh AR, Omidi Y. Ocular novel
drug delivery: Impacts of membranes and barriers.
Expert Opi Drug Del, 2008; 5:567-581.
Sparreboom A, Scripture CD, Trieu V, Williams
PJ, De T, Yang A, Beals B, Figg WD, Hawkins
M, Desai N. Comparative preclinical and clinical
pharmacokinetics of a Cremophor-free,
nanoparticle albumin-bound paclitaxel (ABI-007)
and paclitaxel formulated in cremophor (Taxol).
Clinical Cancer Res, 2005; 11:4136-4143.
Wu Y, Loper A, Landis E, Hettrick L, Novak L,
Lynn K, Chen C, Thompson K, Higgins R, Batra
U, Shelukar S, Kwei G, Storey D. The role of
biopharmaceutics in the development of a clinical
nanoparticle formulation of MK-0869: A Beagle
dog model predicts improved bioavailability and
diminished food effect on absorption in human.
Int J Pharm, 2004; 285:135-146.
Alkhatib R, Hennebelle T, Joha S, Idziorek T,
Preudhomme C, Quesnel B, Sahpaz S, Bailleul F.
Activity of elaeochytrin A from Ferula
elaeochytris on leukemia cell lines.
Phytochemistry, 2008; 69:2979-2983.
Moghimi SM, Hunter AC, Murray JC. Longcirculating and target - specific nanoparticles:
theory to practice. Pharmacol Rev 2001; 53:283-318.
Liu SQ, Tong YW, Yang YY. Incorporation and
in vitro release of doxorubicin in thermally
sensitive micelles made from poly(Nisopropylacrylamide-co-N,Ndimethylacrylamide)-b- poly(D,L-lactide-coglycolide) with varying compositions.
Biomaterials, 2005; 26:5064-5074.
Gupta AK, Madan S, Majumdar DK, Maitra A.
Ketorolac entrapped in polymeric micelles:
Preparation, characterisation and ocular antiinflammatory studies. Int J of Pharm, 2000;
:1-14.
