Modulation of Dendritic Cells by Lipid Grafted Polyelectrolyte Microcapsules

Abstract

Polyelectrolyte microcapsules are fabricated by layer-by-layer deposition of dextran sulfate and poly-L -arginine layers at the surface of calcium carbonate template microparticles followed by core removal to produce hollow microcapsules. In the context of vaccination, these biodegradable LbL capsules emerge as promising antigen carriers and are believed to have potential for the co-delivery of antigens and immunomodulators associated within the same particle to enhance and steer the type of immune response. To this end, it is shown that LbL microcapsules can be functionalized at their surface with lipid layers containing immunopotentiators of lipid nature. The potency of the different lipid modifi ed microcapsules to activate dendritic cells (DCs) is demonstrated by increased expression levels of the migration marker CCR7 and the maturation markers CD40 and CD86. Additionally, the DCs cytokine secretion profi le is evaluated. The fi ndings reveal that the lipid grafted microcapsules are superior to non-modifi ed microcapsules in DC activation and suggest their potential as immune modulating antigen delivery systems.

Spectroscopic Study of the Interaction of Carboxyl-Modified Gold Nanoparticles with Liposomes of Different Chain Lengths and Controlled Drug Release by Layer-by-Layer Technology

“…The capsules were formed by coating of liposome–AuC assemblies with polymer and lipid following an LBL fashion. , The liposome–AuC assembly was prepared by adding excess AuC to freshly prepared liposome solution followed by incubation for nearly 12 hours.…”

“…For the lipid-coated layer, the polymercoated system (i.e., liposome−AuC−P) solution was incubated with the negatively charged liposomes (DMPC:DMPG, prepared in a ratio of 8:2) for 30 min above the phase transition temperature of the negatively charged liposome. 70 The coating conditions for each formulation were optimized beforehand. The optimal AuC, polymer, or lipid to capsule ratio was obtained experimentally by zeta potential values as obtained by titration of the respective capsules upon gradual addition of the polymer or lipid, respectively.…”

“…The resulting capsules were stable against further growth and remained unaggregated in solution. The capsules formed were also capable of creating a barrier to prevent premature release of the drug. − …”

Layer-by-Layer technique as a versatile tool for gene delivery applications

“…Although the LbL platform is still in its infancy and the data regarding the delivery of genetic material in vivo are limited, some important results were already demonstrated in preclinical studies of other LbL particles, which were stable in biological fluids and improved the pharmacokinetic profiles of the therapeutics as well as enhanced the safety and circulation halflife of the drug in vivo, proving a high clinical relevance of the platform [155,156]. By varying the particle diameter, and the charge and thickness of the LbL capsule wall, the distribution of the carriers in vivo may be tuned with control over the cargo release rate, depending on the specific aims [32].…”

Subunit Vaccine Delivery

“…This system was modifi ed with immunopotentiators to further activate DCs. Thus, a pulmonary adaptive immune response was stimulated, which was characterized by induction of a strong Th17-polarized response (De Koker et al 2009b ;De Temmerman et al 2012 ). PMA SH /PVPON polyelectrolyte capsules, which are controllable in their size and peptide vaccine loading, were designed to disintegrate and release the peptide vaccine by rupture of disulfi de linkages upon exposure to reductive conditions.…”