DEVELOPMENT OF PEG-COATED LIPOPLEXES TO BE
INCORPORATED INTO MUCOADHESIVE HEC-SPONGES
Tania Furst1, Anna Lechanteur1,2, Pascale Hubert2, Brigitte Evrard1, Graldine Piel1
Laboratory of Pharmaceutical Technology and Biopharmacy - CIRM, University of Liege (4000), Belgium
Laboratory of Experimental Pathology GIGA Cancer, University of Liege (4000), Belgium
E-mail : [email protected]
This research has a double objective:
Firstly, the preparation of cationic nanovectors, liposomes, which are elaborated for a topical administration into
Liposomes are complexed with siRNA to form lipoplexes. DSPE-PEG2000, an hydrophilic polymer, is added to
lipoplexes to facilitate their diffusion through cervico-vaginal mucus. These lipoplexes must have good
physicochemical characteristics to be effective. They also have to be stable in acidic environment (vaginal pH 4 - 4.5)
and do not release the siRNA.
Secondly, we would like to incorporate these lipoplexes into hydroxyethylcellulose (HEC) gels, which will be freezedried to form sponges. For that, we must first characterize these sponges. They have to be malleable to facilitate
to adhere to the vaginal mucosa and to rehydrate in a short time to allow the diffusion of
A. Preparation and characterization of liposomes, lipoplexes and lipoplexes-PEG
Lipoplexes and PEG-coated lipoplexes in acidic environment
Liposomes are prepared from a mixture of 3 lipids: DOTAP/Chol/DOPE 1/0.75/0.5
+ siRNA lipoplexes with >95% of encapsulation at N/P=2.5
Z-average diameter (nm)
zeta potential (mV)
There is no leakage of siRNA when
lipoplexes 1/0.75/0.5 are in contact
with acidic pH.
Table 1. physicochemical characteristics of liposomes and
DSPE-PEG2000 is added by the post-insertion technique (from 10 to 100 mol% of DOTAP)
When the pH becomes increasingly acidic,
there is no variation in size (around 200nm)
and zeta potential (around 45mV) and
lipoplexes are stable. (n=3)
Fig.2. Size, PDI and zeta potential of PEG-coated lipoplexes
(A) When the % of PEG increases, the diameter is ranged between 150 and 220nm. Up 50%, PDI
< 0.2 but from this %, lipoplexes are more polydispersed and PDI > 0.5.
(B) The zeta potential decreases from +50mV to -20mV when the % of PEG increases.
B. Preparation and characterization of HEC hydrogels and
The gels (6g) are prepared by homogeneization of HEC 250M, PEG 400 and milliQ water
The sponges are obtained after freeze-drying (24hours)
The mucoadhesion is characterized with a Texture Analyzer
mucin discs (250mg) and synthetic cervical mucus are used
HEC 250M (mg)
Fig.5. Size of PEG-coated lipoplexes
The sizes of the different pegylated
lipoplexes seem to be constant (around
200nm) when the pH is acidic. (n=1)
Force Minimale: -0,030999 N
Adhesiveness: 0,097689 Nmm
Fig.7. SEM images of transversal section of sponges
A, B and C respectively.
The strucutre of the pores is also related to the viscosity of
the gels before freeze-drying.
When the viscosity
increases, the pores are more numerous and organized.
F min = adhesion force
Fig.5. Example of graph
obtained with the TA to
quantify the mucoadhesion.
Fmin represents the adhesion
force of the gel/sponge with the
Fig.6. Mucadhesion of the gels and the sponges
(A) The mucoadhesion of the gels is measured before and after lyophilization and rehydration with
synthetic cervical mucus (2.5ml). When the viscosity of the gel increases the mucoadhesion increases
(B) The mucoadhesion of the sponges is consistent with the one of the gels. The more the viscosity of
the gels increases, the more the mucoadhesion increases. (n=15)
3. CONCLUSION AND PERSPECTIVES
Lipoplexes DOTAP/Chol/DOPE 1/0.75/0.5 at N/P=2.5 with and without PEG have good physicochemical characteristics. Moreover, they seem to be stable in
acidic pH, there is no leakage of siRNA and their sizes remain constant.
Other studies will be realized to verify their efficacy and stability in mucus, in the gel and after lyophilization.
Regarding sponges, HEC 250M seems to be an ideal polymer to form a mucoadhesive system.
A balance between the viscosity and the mucoadhesion need to be selected to obtain an optimal system to further incoporate lipoplexes.
The deformability and the hardness of the sponges will also be characterized with the Texture Analyzer
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