4 research outputs found
Design of a Homogeneous Multifunctional Supported Lipid Membrane on Layer-by-Layer Coated Microcarriers
Key challenges in the development
of drug delivery systems are
the prevention of serum compartment interaction and the targeted delivery
of the cargo. Layer-by-Layer microcarriers offer many advantages due
to various options in drug assembly and multifunctional design. Surface
modification with a supported lipid membrane enhances biocompatibility,
drug protection ability, and specific functionality. However, the
integration of functionalized lipids strongly influences the membrane
formation and is often accompanied by submicrometer irregularities:
The accessibility of underlying polymers to serum components may change
the carrier’s properties and enhances the susceptibility to
opsonization. Therefore, the formation of a tightly assembled multifunctional
lipid membrane has been emphasized. A phosphatidylserine/phosphatidylcholine
(POPS/POPC) bilayer equipped with phosphatidylethanolamine–polyethylene
glycol–biotin (PE-PEG-Biotin) was used to facilitate a biotin/streptavidin
binding site for a variable attachment of an additional function,
such as antibodies for specific targeting. Thus, a prefunctionalized
carrier where only the outer functionality needs to be replaced without
disturbing the underlying structure could be created
Specific Uptake of Lipid-Antibody-Functionalized LbL Microcarriers by Cells
The
modular construction of Layer-by-Layer biopolymer microcarriers
facilitates a highly specific design of drug delivery systems. A supported
lipid bilayer (SLB) contributes to biocompatibility and protection
of sensitive active agents. The addition of a lipid anchor equipped
with PEG (shielding from opsonins) and biotin (attachment of exchangeable
outer functional molecules) enhances the microcarrier functionality
even more. However, a homogeneously assembled supported lipid bilayer
is a prerequisite for a specific binding of functional components.
Our investigations show that a tightly packed SLB improves the efficiency
of functional components attached to the microcarrier’s surface,
as illustrated with specific antibodies in cellular application. Only
a low quantity of antibodies is needed to obtain improved cellular
uptake rates independent from cell type as compared to an antibody-functionalized
loosely packed lipid bilayer or directly assembled antibody onto the
multilayer. A fast disassembly of the lipid bilayer within endolysosomes
exposing the underlying drug delivering multilayer structure demonstrates
the suitability of LbL-microcarriers as a multifunctional drug delivery
system
Reversible Fusion Proteins as a Tool to Enhance Uptake of Virus-Functionalized LbL Microcarriers
For
the efficient treatment of an increasing number of diseases
the development of new therapeutics as well as novel drug delivery
systems is essential. Such drug delivery systems (DDS) must not only
consider biodegradability and protective packaging but must also target
and control the release of active substances, which is one of the
most important points in DDS application. We highlight the improvement
of these key aspects, the increased interaction rate of Layer-by-Layer
(LbL) designed microcarriers as a promising DDS after functionalization
with vesicular stomatitis virus (VSV). We make use of the unique conformational
reversibility of the fusion protein of VSV as a surface functionalization
of LbL microcarriers. This reversibility allows for VSV to be used
both as a tool for assembly onto the DDS and as an initiator for an
efficient cellular uptake. We could show that the evolutionary optimized
viral fusion machinery can be successfully combined with a biophysical
DDS for optimization of its cellular interaction
Influence of Growth Characteristics of Induced Pluripotent Stem Cells on Their Uptake Efficiency for Layer-by-Layer Microcarriers
Induced pluripotent stem cells (iPSCs)
have the ability to differentiate
into any specialized somatic cell type, which makes them an attractive
tool for a wide variety of scientific approaches, including regenerative
medicine. However, their pluripotent state and their growth in compact
colonies render them difficult to access and, therefore, restrict
delivery of specific agents for cell manipulation. Thus, our investigation
focus was set on the evaluation of the capability of layer-by-layer
(LbL) designed microcarriers to serve as a potential drug delivery
system to iPSCs, as they offer several appealing advantages. Most
notably, these carriers allow for the transport of active agents in
a protected environment and for a rather specific delivery through
surface modifications. As we could show, charge and mode of LbL carrier
application as well as the size of the iPSC colonies determine the
interaction with and the uptake rate by iPSCs. None of the examined
conditions had an influence on iPSC colony properties such as colony
morphology and size or maintenance of pluripotent properties. An overall
interaction rate of LbL carriers with iPSCs of up to 20% was achieved.
Those data emphasize the applicability of LbL carriers for stem cell
research. Additionally, the potential use of LbL carriers as a promising
delivery tool for iPSCs was contrasted to viral particles and liposomes.
The identified differences among those delivery tools have substantiated
our major conclusion that LbL carrier uptake rate is influenced by
characteristic features of the iPSC colonies (most notably colony
size) in addition to their surface charges