Formulation and immunological evaluation of novel vaccine delivery systems based on bioresorbable poly(ethylene glycol)‐block‐poly(lactide‐co‐ε‐caprolactone)

Abstract

Novel emulsion-type vaccine delivery systems based on the amphiphilic bioresorbable polymer poly(ethylene glycol)-block-poly(lactide-co-epsilon-caprolactone) (PEG-b-PLACL) and selected oils were developed here. Physicochemical characterizations such as stability, a droplet test, microscopic aspects, and in vitro release showed that PEG-b-PLACL-emulsified formulations have several advantages over traditional vaccine adjuvants in that they are stable, reproducible, and homogeneous fine particles with an appropriate size to facilitate the induction of potent immune responses. Different dispersion-type emulsions have provided different release profiles using ovalbumin in model studies. Immunogenicity studies in mice have shown that antigen-specific antibody titers and T-cell proliferative responses, as well as the secretion of IFN-gamma, were significantly enhanced for ovalbumin after formulation with PEG-b-PLACL-based emulsions. These features are of great interest for applications in delivery systems of prophylactic and therapeutic vaccine candidates.

Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy

“…ethoxylated sorbitan fatty acid esters (known as Tween ® ). However, it has been well documented that Tween ® series may cause toxicities including severe non-immunological anaphylactoid reactions67. Here we use PEG-b-PLACL/Span ® 85 as surface-active components to stabilize oil/water interfaces, rendering emulsified PELC particles.…”

“…2). This finding was assigned to the fact that the presence of excipient Span ® 85 in the oily phase may not only play an important role in governing the dispersion properties of the emulsion but also provide a potential way to stabilize PELC particles7. However, these parameters are strongly influenced by an optimization of the emulsification process and the surfactant system.…”

“…The AB-type diblock copolymer PEG-b-PLACL was synthesized by ring-opening polymerization of DL-lactide and ε-caprolactone in the presence of polyethylene glycol 5,000 monomethyl ether and SnOct 2 67. Ovalbumin (OVA, Grade V) was purchased from Sigma-Aldrich (MO, USA).…”

“…This idea is based on the use of amphiphilic bioresorbable polymers as hydrophilic emulsifiers to stabilize the aqueous/oily interfaces, rendering an emulsion with oil droplets dispersed into the aqueous solution6789. We proposed that the polymeric emulsifier can stabilize the emulsion during preparation and storage678; on the other hand, its degradable nature predominates that the emulsion can be destroyed and further to be absorbed post-vaccination9. Among these, we optimized a ready-to-use emulsion adjuvant, which dubbed PELC, comprised of phosphate-buffered saline (PBS), squalene oil, the lipophilic emulsifier Span ® 85 (sorbitan trioleate), and the bioresorbable poly(ethylene glycol)-block-poly(lactide-co-ε-caprolactone) (PEG-b-PLACL)10.…”

Preparation and evaluation of SiO2-deposited stearic acid-g-chitosan nanoparticles for doxorubicin delivery

“…The size of polymeric micelles is generally on the nanoscale (10-100 nm) and can spontaneously accumulate in tumor tissues through their well-known "enhanced permeability and retention (EPR) effect," 3 marking it as a candidate carrier for antitumor drugs. In addition, the surface charge of polymeric micelles makes them suitable as carriers for biomacromolecules such as genes, [4][5][6] vaccines, 7 and protein drugs, 8 protecting these biomacromolecules from degradation via oral drug delivery systems.…”