Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 85

cardiovascular applications, 31 resulted in localized protein delivery im-
proving the outcome of the therapy.
Selection of an accurate size of liposomes when designing lipid-based
DDSs is critical because, the larger the DDS, the higher the possibility to face
various barriers within the host such as endothelial surfaces or the blood-
brain or to become targets of the immune system. 69
A wide range of methods has been employed in liposome manufacture.
Each process has advantages and limitations that should be considered with
respect to the individual application. Below we mention some of them:

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Dried films: these films are formed by roto-evaporation of a solvent
mixture containing phospholipids. An aqueous phase containing a
hydrophilic protein in solution is added to the dry film. This is the
easiest process to fabricate lipo-based DDS, but usually the protein
leaks out of the membrane preventing its controlled released.
Freeze-and-thaw liposomes: submitting vesicles to freeze-thaw cycles or
lyophilization seems to avoid protein leakiness and enhances en-
capsulation although it is important to evaluate the effects of tem-
perature variations on the protein bioactivity.
Solvent-requiring methods: the manufacturing process consists of an
aqueous solution that is momentarily emulsified into an immiscible
organic phase containing the required lipids; rapid removal of solvent
induces formation of inverse micelle intermediates which upon hy-
dration organize into bilayered liposomes. The protein of interest is
present in the solvent. 71

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The release of drug from liposomes is related to both lipid composition
and type of liposome constructed. DDSs made of liposomes can be ad-
ministrated intramuscularly or subcutaneously, orally, through the eye,
intranasally or topically and this versatility increases the number of clinical
applications of liposomes.
Hedman et al. initiated a clinical trial in which a plasmid-encoding
VEGF was delivered using liposomes during angioplasty and stenting for
the treatment of chronic myocardial ischemia. 72 Currently, there are no
liposomal formulations approved for human use for the treatment of car-
diovascular disease nevertheless, liposomes have evolved as robust multi-
functional platforms for drug delivery, with several innovative examples
currently being examined in preclinical models of diverse diseases including
infarction.
Solid lipid particulate systems appeared as alternative GF carriers to
polymeric particles; however, there are only a few reports demonstrating its
effectiveness as angiogenic proteins carriers for cardiac repair. Oh et al.re-
ported the formation of a temperature-induced gel composed of core-shell
nanoparticles for ischemic heart regeneration. 73 The particle core was
composed of lecithin containing VEGF and the shell was composed of
Pluronic-F127 (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene