Search

Transcutaneous immunization receives much attention due to the recognition of a complex network of immunoregulatory cells in various layers of the skin. The elaboration of non-invasive needle-free approaches towards antigen delivery holds especially great potential here while searching for a hygienically optimal vaccination strategy. Here, we report on a novel protocol for transfollicular immunization aiming at delivery of an inactivated influenza vaccine to perifollicular antigen presenting cells without disrupting the stratum corneum integrity. Porous calcium carbonate (vaterite) submicron carriers and sonophoresis were utilized for this purpose. Transportation of the vaccine-loaded particles into hair follicles of mice was assessed in vivo via optical coherence tomography monitoring. The effectiveness of the designed immunization protocol was further demonstrated in an animal model by means of micro-neutralization and enzyme-linked immunosorbent assays. The titers of secreted virus-specific IgGs were compared to those obtained in response to intramuscular immunization using conventional influenza vaccine formulation demonstrating no statistically significant differences in antibody levels between the groups. The findings of our pilot study render the intra-follicular delivery of the inactivated influenza vaccine by means of vaterite carriers a promising alternative to invasive immunization. [ABSTRACT FROM AUTHOR]

The lack of an efficient and versatile intracellular nucleic acids delivery platform impedes the clinical implementation of gene therapy. Advances in layer‐by‐layer (LbL) technology have led to the production of LbL polymer capsules, a promising universal delivery tool. The biocompatibility, sufficient packaging capacity, safety, low cost, and high variability of structure and composition of the LbL capsules make it possible to meet the requirements for clinical‐grade nonviral gene transfer. Here, the possibility of polymeric LbL capsules of different sizes (micrometer and sub‐micrometer‐sized) to serve as universal nonviral carriers for messenger RNA (mRNA) and small interfering RNA (siRNA) is considered. In particular, the internalization of capsules into human mesenchymal stem cells (hMSCs, as an example of adult primary stem cells), capsule uptake, and intracellular delivery of mRNA and siRNA is studied. Importantly, the use of micrometer‐ or sub‐micrometer‐sized polymer capsules (MicCaps and SubCaps) allows the mRNA or siRNA to be packaged and transferred into hMSCs with high efficiency. While the uptake efficiency is comparable between MicCaps and SubCaps, the latter are significantly more efficient than MicCap when transferring siRNAs. These results demonstrate the potential of the LbL capsules as a universal gene delivery platform, which can be tuned according to the properties of genetic cargo. [ABSTRACT FROM AUTHOR]

Actinium-225 ( 225 Ac) radiolabeled submicrometric core-shell particles (SPs) made of calcium carbonate (CaCO 3 ) coated with biocompatible polymers [tannic acid-human serum albumin (TA/HSA)] have been developed to improve the efficiency of local α-radionuclide therapy in melanoma models (B16-F10 tumor-bearing mice). The developed 225 Ac-SPs possess radiochemical stability and demonstrate effective retention of 225 Ac and its daughter isotopes. The SPs have been additionally labeled with zirconium-89 ( 89 Zr) to perform the biodistribution studies using positron emission tomography-computerized tomography (PET/CT) imaging for 14 days after intratumoral injection. According to the PET/CT analysis, a significant accumulation of 89 Zr-SPs in the tumor area is revealed for the whole investigation period, which correlates with the direct radiometry analysis after intratumoral administration of 225 Ac-SPs. The histological analysis has revealed no abnormal changes in healthy tissue organs after treatment with 225 Ac-SPs (e.g., no acute pathologic findings are detected in the liver and kidneys). At the same time, the inhibition of tumor growth has been observed as compared with control samples [nonradiolabeled SPs and phosphate-buffered saline (PBS)]. The treatment of mice with 225 Ac-SPs has resulted in prolonged survival compared to the control samples. Thus, our study validates the application of 225 Ac-doped core-shell submicron CaCO 3 particles for local α-radionuclide therapy.