Potensi Kombinasi Nanopartikel Kitosan dan Propolis sebagai Kandidat Adjuvant Vaksin Human Papillomavirus (HPV): Studi Preformulasi Sediaan Oral dan Uji In Vivo

Alvian Chesyar Burhanudin, Dr. apt. Adhyatmika, M.Biotech.; Dr. apt. Soni Siswanto, M.Biomed.

2026 | Skripsi | FARMASI

Infeksi HPV merupakan salah satu penyakit menular seksual penyebab kanker serviks. WHO tahun 2020 melaporkan sebanyak 36.633 wanita di Indonesia menderita kanker serviks dengan kasus kematian mencapai 57,3%. Vaksinasi masih menjadi strategi utama dalam mengendalikan transmisi HPV, namun tingginya biaya produksi serta persepsi negatif masyarakat terhadap vaksin HPV membatasi cakupan vaksinasi. Vaksin oral menawarkan alternatif yang menjanjikan karena lebih praktis dan berpotensi meningkatkan efektivitas imunisasi. Sistem penghantaran berbasis nanopartikel mampu meningkatkan kinerja vaksin oral dengan melindungi antigen dari degradasi, sementara pengembangan adjuvant turut mendukung peningkatan respons imun. Penelitian ini bertujuan mengkaji potensi nanopartikel kitosan–propolis sebagai kandidat adjuvant vaksin oral VLP HPV-16/18.

Penelitian menggunakan desain true experimental research melalui studi preformulasi dan in vivo. Preformulasi dilakukan dengan protein model albumin, diikuti optimasi surfaktan dengan metode simplex lattice design berdasarkan karakterisasi ukuran partikel, PdI, dan potensial zeta, serta diukur entrapment efficiency (EE%). Preformula vaksin VLP HPV-16/18 diuji stabilitasnya dan in vivo. Hewan uji mencit betina dibagi menjadi kelompok tanpa adjuvant tanpa VLP (K-), adjuvant tanpa VLP (F1), VLP tanpa adjuvant (F2), dan preformula optimal (F3). Permberian secara oral sebanyak tiga kali dengan interval 14 hari dan konsentrasi IgG plasma dianalisis dengan ELISA.

Karakterisasi preformula optimal menunjukkan ukuran partikel sebesar 271,1±1,0 nm, PdI 0,270±0,013, dan potensial zeta 42,667±1,650 mV. Nilai desirability sebesar 1,000 dengan surfaktan PEG 400 1% sebagai komposisi surfaktan paling optimal. Nilai EE% mencapai 91,225% menunjukkan efisiensi enkapsulasi antigen yang tinggi. Uji stabilitas freeze-thaw tidak menunjukkan perubahan signifikan sehingga mengindikasikan stabilitas preformula yang baik. Pengukuran IgG melalui pengujian ELISA dan image-based colorimetry mengungkap temuan kombinasi adjuvant kitosan-propolis pada preformulasi vaksin oral VLP HPV-16/18 efektif dalam meningkatkan titer IgG.

HPV infection is a major sexually transmitted diseases associated with cervical cancer. In 2020, WHO reported 36,633 women in Indonesia suffered from cervical cancer, with a mortality rate of 57.3%. Vaccination remains the primary strategy to control HPV transmission; however, high production costs and negative public perceptions limit its coverage. Oral vaccines offer a promising alternative due to their practicality and potential to improve immunization outcomes. Nanoparticle-based delivery systems can enhance oral vaccine performance by protecting antigens from degradation, while adjuvant development further supports immune response enhancement. This study aimed to examine the potential of chitosan–propolis nanoparticles as candidate adjuvants for an oral HPV-16/18 VLP vaccine.

The study employed a true experimental research design through preformulation and in vivo studies. Preformulation was conducted using albumin model protein, followed by surfactant optimization using simplex lattice design based on characterization of particle size, PdI, and zeta potential, along with entrapment efficiency (EE%). The HPV-16/18 VLP vaccine preformulation underwent stability and in vivo testing. Female mice were divided into groups without adjuvant and without VLP (K-), adjuvant only (F1), VLP only (F2), and the optimal preformulation (F3). Administration was performed orally three times at 14-day intervals. Blood plasma was collected for IgG antibody evaluation through ELISA testing.

Characteristics of preformulation showed a particle size 271.1±1.0 nm, PdI 0.270±0.013, and zeta potential 42.667±1.650 mV. A desirability value was 1.000 with 1% PEG 400 surfactant as the most optimal surfactant composition. The EE% reached 91.225%, indicating efficient antigen encapsulation. Freeze-thaw stability testing showed no significant changes, confirming good stability. Measurements of IgG levels of ELISA and image-based colorimetry revealed that the chitosan-propolis adjuvant combination in the preformulation of an oral VLP HPV-16/18 vaccine’s was effective in increasing IgG titers.

Kata Kunci : HPV, vaccine, adjuvant, chitosan, propolis