Effect of formulation and processing variables on the particle size of sorbitan monopalmitate niosomes

Ebtessam A Essa


In the last two decades, there was an extensive research focused on the study of synthetic amphiphilic vesicles, prepared by nonionic surfactants (niosomes). The particle size of these vesicles is critical for their intended therapeutic benefits.
Formulation and processing factors affect greatly the physical characteristics of the resulted nanosystems. Therefore, the present work was adopted to investigate how proper manipulation of various formulations and processing factors on vesicular Z-average particle size. The selected variables were membrane additives, [including cholesterol (CHO), dicetylphosphate (DCP) and stearylamine (SA)], sonication time as well as drug loading factor (using mannitol and estradiol). Sorbitan monopalmitate (span 40) niosomes were prepared by the conventional thin film hydration method. Particle size, measured by
Photon Correlation Spectroscopy, and polydispersity indices were measured and compared.The results indicated that CHO increased the vesicular size, with 2:1 and 1:1 (span 40:CHO) ratios showing the same size. Sonication reduced the vesicle size by 23, 35 and 42% after 10, 20 and 30 min, respectively. After 30 min, the effect of sonication was minor. The addition of charge inducing agents changed the zeta potential depending on the type of the additives. Surface charge increased the size by 24 and 11% when using DCP and SA, respectively. Drug incorporation increased the vesicle size to an extent based on its aqueous solubility. There were about 35 and 6.2% increase in vesicular size for estradiol and mannitol, respectively, supporting the partitioning of lipophilic drug within the fatty acyl side chains of the bilayer membrane.

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Couvereur P, Fattal E, Andremont A. Liposomes and nanoparticles in

the treatment of intracellular bacterial infections. Pharm Res 1991;8:


Choi MJ, Maibach HI. Liposomes and niosomes as topical drug delivery

systems. Skin Pharmacol Physiol 2005;18:209-19.

Ucheghu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in

drug delivery. Int J Pharm 1998;172:33-70.

Hofland HEJ, Bouwstra JA, Verhoef J, Junginger HE. Niosomes: A study

of structure, stability, drug release and toxicological aspects. J Control

Release 1990;13:325-6.

Litzinger DC, Buiting AM, Vanrooijen N, Huang L. Effect of liposome

size on the circulation time and intraorgan distribution of amphipathic

poly(ethylene glycol)-containing liposomes. Biochim Biophys Acta


Goyal P, Goyal K, Kumar SG, Singh A, Katare OP, Mishra DN. Liposomal

drug delivery systems: Clinical applications. Acta Pharm 2005;55:1-25.

Verma DD, Verma S, Blume G, Fahr A. Particle size of liposomes

influences dermal delivery of substances into skin. Int J Pharm


entjurc M, Vrhovnik K, Kristl J. Liposomes as a topical delivery system:

The role of size on transport studied by the EPR imaging method. J

Control Rel 2000;59:97-7.

Szoka FC, Milholland JD, Barza M. Effect of lipid composition and

liposome size on toxicity and in vitro fungicidal activity of liposome-

intercalated amphotericin B. Antimicrob Agents Chemother 1987;31:


Shi B, Fang C, Pei Y. Stealth PEG-PHDCA niosomes: Effects of chain length of PEG and particle size on niosomes surface properties, in vitro drug release, phagocytic uptake, in vivo pharmacokinetics and antitumor

activity. J Pharm Sci 2006;95:1873-7.

Nagayasu A, Shimooka T, Kinouchi Y, Uchiyama K, Takeichi Y, Kiwada

H. Effect of fluidity and vesicle size on antitumor activity and

mylosuppressive activity of liposomes loaded with daunorbbicin. Biol

Pharm Bull 1994;7:935-9.

Volodkin D, Mohwald H, Jean-Claude Voegel J, Ball V. Coating of

negatively charged liposomes by polylysine: Drug release study. J Contol

Rel 2007;117:111-20.

New RRC. Liposomes; A practical Approach. Oxford: Oxford University

Press; 1990.

Montengero L, Panico AM, Ventimiglia A, Bonina FP. In vitro retinoic acid release and skin permeation from different liposome formulations. Int

J Pharm 1996;133:89-6.

Essa EA, Booner M, Barry BW. Targeted transdermal delivery of drugs

using charged liposomes. PhD thesis (2003). University of Bradford

Bradford, UK;.

Needham D, Nunn RS. Elastic deformation and failure of lipid bilayer

membranes containing cholesterol. Biophys J 1990;58:997-9.

Uchegbu IF, Bouwstra JJ, Florence AT. Large disk-shaped vesicles

(discomes) in vesicle-to-micelle transitions. J Phys Chem 1992;96:


McIntosh TJ. The effect of cholesterol content on the structure of

phosphatidylcholine bilayers. Biochim Biophys Acta 1978;51:43-58.

Fang J, Hong CT, Chiu W, Wang YY. Effect of liposomes and niosomes

on skin permeation of enoxacin. Int J Pharm 2001;219:61-2.

Lopez-Pinto JM, Gonzalez-Rodriguez ML, Rabasco AM. Effect of

cholesterol and ethanol on dermal delivery from DPPC liposomes. Int

J Pharm 2005;298:1-12.

Lee SC, Lee KE, Kim JJ, Lim SH. The effect of cholesterol in the

liposome bilayer on the stability of incorporated retinol. J Liposome

Res 2005;15:157-6.

Silver L. The physical chemistry of membranes. New York, USA Alan and

Unwin and Soloman PressUchegbu IF, Florence AT. Non-ionic surfactant

vesicles (Niosomes): Physical and pharmaceutical chemistry. Adv Colloid

Interface Sci 1995;58:1-55.

Moriyam E, Saito T, Tokuoka Y, Takeuchi S, Kawashima N. Evaluation of

the hardness of lipid bilayer membranes of liposomes by the ultrasound

attenuation method. J Oleo Sci 2003;52:433-7.

Richardson ES, Pitt WG, Woodbury DJ. The role of cavitation in liposome

formation. Biophys J 2007;12:4100-7.

Brennen CE. Cavitation and bubble dynamics. New York: Oxford

University Press; 1995.

Lasic DD. The mechanism of vesicle formation. Biochem J 1988;256:1-11.

Lasic DD. Mechanisms of liposome formation. J Liposome Res


Yamaguchi T, Nomura M, Matsuoka T, Koda S. Effects of frequency and

power of ultrasound on the size reduction of liposomes. Chem Phys

Lipos 2009;160:58-2.

Krasnici S, Werner A, Martin E, Eichhorn ME, Schmitt-Sody M, Pahernik

SA, et al. Effect of the surface charge of liposomes on their uptake by

angiogenic tumor vessels. Int J Cancer 2003;105:561-7.

Li Y, Mitra AK. Effects of phospholipid chain length, concentration,

charge, and vesicle size on pulmonary insulin absorption. Pharm Res


Azmin MN, Florence AT, Handjani-Vila RM, Stuart FB, Vanlerberghe

G, Whittaker JS. The effect of non-ionic surfactant vesicles (niosome)

entrapment on the absorption and distribution of methotrexate in

mice. J Pharm Pharmacol 1985;37:237-2.

Carafa M, Santucci E, Alhaique F, Coviello T, Murtas E, Riccieri FM,

et al. Preparation and properties of new unilamellar non-ionic/ionic

surfactant vesicles. Int J Pharm 1998;160:51-9.

Van Hal DA, Bouwstra JA, Rensen AV, Jermiasse E, Vringer TD, Junginger

HE. Preparation and characterization of non-ionic surfactant vesicles.

J Colloid Interface Sci 1996;178:263-3.

Pardakhty A, Varshosaz J, Rouholamini A. In vitro study of

polyoxyethylene alkyl ether niosomes for delivery of insulin. Int J

Pharm 2007;328:130-1.

Junyapraset VB, Teeranachaideekul V, Supapem T. Effect of charged

and non-ionic membrane additives on physicochemical properties and

stability of niosomes. AAPS PharmSciTech 2008;9:851-9.

Chrai SS, Murari R, Ahmed I. Liposomes (a review). Part two: drug

delivery systems. BioPharm. 2002;15:40-9.

Schwender RA, Asanger M, Weder HG. N-alkyl-glucosides as detergents

for the preparation of highly homogenous bilayer liposomes of visible

size (60-240 nm) applying defined rates of detergent removal by dialysis.

Biochem Biophys Res Commun 1981;10:1055-2.

Gayatri DS, Venkatesh P, Udupa N. Niosomal sumatriptan succinate for

nasal administration. Indian J Phama Sci 2000;62:479-1.

DOI: http://dx.doi.org/10.22377/ajp.v4i4.289


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