Microneedles with dual release pattern for improved immunological efficacy of Hepatitis B vaccine

Ji Seok Kim; Jung-Ah Choi; Jong Chan Kim; Hayan Park; Eunji Yang; Ji Sun Park; Manki Song; Jung-Hwan Park

doi:10.1016/j.ijpharm.2020.119928

Microneedles with dual release pattern for improved immunological efficacy of Hepatitis B vaccine

Int J Pharm. 2020 Dec 15:591:119928. doi: 10.1016/j.ijpharm.2020.119928. Epub 2020 Oct 16.

Authors

Ji Seok Kim¹, Jung-Ah Choi², Jong Chan Kim¹, Hayan Park², Eunji Yang², Ji Sun Park², Manki Song³, Jung-Hwan Park⁴

Affiliations

¹ Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam, Republic of Korea.
² Science Department, International Vaccine Institute, Seoul, Republic of Korea.
³ Science Department, International Vaccine Institute, Seoul, Republic of Korea. Electronic address: mksong@ivi.int.
⁴ Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam, Republic of Korea. Electronic address: pa90201@gachon.ac.kr.

PMID: 33069897
DOI: 10.1016/j.ijpharm.2020.119928

Abstract

In this study, dissolving microneedles (DMNs) with dual-release pattern, capable of both bolus release and slow release, were prepared. These DMNs were used with a hepatitis B vaccine that requires multiple shots to achieve immunological efficacy comparable to that obtained when two separate shots are administered. Dissolving microneedles with HBsAg in PLA tips and CMC coating formulation together (HBsAg-PLA/CMC-DMNs) consist of polylactic acid (PLA) tips for slow release, a carboxy-methyl cellulose (CMC) coating formulation for bolus release, and a dissolving base of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) for dissolution in the skin. The in vitro release pattern of HBsAg from the CMC coating formulation and PLA tips was observed. Through an in vivo test, 1) the delivery efficiency of HBsAg-PLA/CMC-DMNs was observed, and 2) the immunological efficacy of this method was compared with the efficacy of two shots delivered by conventional intramuscular (IM) administration and two shots delivered by HBsAg-coated microneedle (CMNs) administration. HBsAg-PLA/CMC-DMNs punctured the skin successfully. The PVA/PVP base was completely dissolved within 10 min of insertion, resulting in the delivery of all microneedle tips into the skin. In the in vitro release experiment, all of the HBsAg in the CMC coating formulation was released within 20 min, and the HBsAg present in the PLA tips was gradually released over more than 55 days. The antibody titer of one shot of HBsAg-PLA/CMC-DMNs was the same as or higher than two shots delivered by conventional IM and CMN methods. DMNs with dual-release pattern can deliver two formulations simultaneously with a single shot, resulting in improved immunological efficacy of HBsAg that requires multiple doses. In addition, this dual-release MN system can be used for the delivery of other drugs that require multiple administrations.

Keywords: Dual release pattern; Hepatitis B vaccine; Improved immunological efficacy; Microneedles.

MeSH terms

Administration, Cutaneous
Drug Delivery Systems
Hepatitis B Surface Antigens
Hepatitis B Vaccines*
Needles*
Povidone
Skin

Substances

Hepatitis B Surface Antigens
Hepatitis B Vaccines
Povidone