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The Shape/Morphology Balance: A Study of Stealth Liposomes via Fractal Analysis and Drug Encapsulation

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ABSTRACT

Purpose

Fractal analysis was used as a tool in order to study the morphological characteristics of PEGylated liposomes. We report on the morphological characteristics of stealth liposomes composed of DPPC and DPPE-PEG 3000 in two dispersion media using fractal analysis.

Methods

Light scattering techniques were used in order to elucidate the size, the morphology and the surface charge of PEGylated liposomes as a function of PEGylated lipid concentration and temperature. Fluorescence spectroscopy studies revealed a microenvironment of low polarity inside the liposomal membranes.

Results

All formulations were found to retain their physicochemical characteristics for at least 3 weeks. The hydrodynamic radii (Rh) of stealth liposomes were stable in the process of heating up to 50°C; while the fractal dimension values (df) which correspond to their morphology, have been changed during heating. Hence, these results are a first indication of the presence of a heterogeneous microdomain structure of the stealth liposomal system. The amphiphilic drug indomethacin (IND) was successfully encapsulated within the liposomes and led to an increased size of stealth liposomes, while the morphology of liposomal vectors changed significantly at the highest molar ratio of PEGylated lipid.

Conclusions

We can state that this approach can promote a new analytical concept based on the morphological characteristics and quantify the shape of drug carriers complementary to that of the conventional analytical techniques.

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Abbreviations

df :

mass fractal

DLCA:

diffusion-limited cluster aggregation

DPPC:

1,2-dipalmitoyl-sn-glycero-3-phosphocholine

DPPE-PEG 3000:

1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[Methoxy(Polyethylene glycol)-3000]

ds :

surface fractal

IND:

indomethacin

NSAIDs:

nonsteroidal anti-inflammatory drugs

PBS:

phosphate buffer saline

RLCA:

reaction-limited cluster aggregation

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Athens, Panepistimioupolis Zografou, 157 71, Athens, Greece

    Natassa Pippa, Faidra Psarommati & Costas Demetzos

  2. Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35, Athens, Greece

    Natassa Pippa & Stergios Pispas

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  1. Natassa Pippa
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  2. Faidra Psarommati
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  3. Stergios Pispas
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  4. Costas Demetzos
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Correspondence to Costas Demetzos.

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Pippa, N., Psarommati, F., Pispas, S. et al. The Shape/Morphology Balance: A Study of Stealth Liposomes via Fractal Analysis and Drug Encapsulation. Pharm Res 30, 2385–2395 (2013). https://doi.org/10.1007/s11095-013-1082-8

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  • DOI: https://doi.org/10.1007/s11095-013-1082-8

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