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All Journal Reaktor Proceedings of Annual International Conference Syiah Kuala University - Life Sciences & Engineering Chapter Jurnal Sains Materi Indonesia Media Farmasi : Jurnal Ilmu Farmasi (Journal Of Pharmaceutical Science) Journal of Engineering and Technological Sciences Acta Pharmaceutica Indonesia JFIOnline Journal of halal product and research (JHPR) Jurnal Riset Kefarmasian Indonesia Narra J
Diky Mudhakir
School Of Pharmacy, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung 40132, Indonesia
Religion Agriculture, Biological Sciences & Forestry Humanities Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Control & Systems Engineering Dentistry Economics, Econometrics & Finance Energy Engineering Health Professions Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Nursing Public Health Social Sciences Veterinary Other

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Journal : Narra J

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Enhanced delivery of anti-inflammatory therapeutics using pH-responsive histidine-modified poly-L-lysine on mesoporous silica nanoparticles Permana, Zuliar; Xeliem, Jovinka N.; Zefrina, Normalita F.; Hanum, Latifa F.; Nirmalayanti, Ni LPKV.; Permana, Benny; Mudhakir, Diky
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1815

Abstract

Mesoporous silica nanoparticles (MSNs) are effective platforms for drug delivery due to their high surface area, adjustable pore sizes, and biocompatibility. The aim of this study was to explore the application of histidine-modified poly-L-lysine (PLL-His) as a pH-responsive gatekeeper to control the release of an anti-inflammatory agent, celecoxib, from MSNs. MSNs were synthesized through a sol-gel process using cetyltrimethylammonium bromide (CTAB) as a template and were functionalized with amine groups using (3-aminopropyl)triethoxysilane (APTES). Drug loading was achieved via adsorption in ethanol. Subsequently, poly-L-lysine (PLL) and PLL-His were conjugated to the MSNs using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) and N-hydroxysuccinimide (NHS) to form MSN-NH2-Drug-PLL and MSN-NH2-Drug-PLL-His constructs. Characterization of these particles was conducted using Fourier-transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) analysis, and particle size analysis. Results showed that the particle size of MSN-NH2-drug-PLL and MSN-NH2-drug-PLL-His was 237.10±6.56 nm and 234.03±14.65 nm, respectively, indicating suitability for cellular uptake. BET analysis confirmed the increased surface area and pore volume after the removal of CTAB, demonstrating successful mesopore formation. Drug release tests were performed in simulated gastric (pH 1.2) and physiological (pH 7.4) conditions, showing that PLL-His-modified MSNs exhibited minimal release in acidic conditions and sustained release at physiological pH. The PLL-His effectively functioned as a pH-responsive gatekeeper, enhancing drug targeting and reducing premature release. This study highlights the potential of PLL-His-modified MSNs as a promising model for pH-sensitive, targeted drug delivery, with potential applications across various therapeutic areas requiring precise release profiles. This approach could significantly improve therapeutic outcomes and patient compliance, particularly in disease contexts where pH variability is a critical factor. Overall, the integration of PLL-His as a pH-responsive gatekeeper represents a significant advancement in the design of smart drug delivery systems.
Design of lipid nanoparticle (LNP) containing genetic material CRISPR/Cas9 for familial hypercholesterolemia Prasetia, I GNJA.; Kurniati, Neng F.; Riani, Catur; Mudhakir, Diky
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.2217

Abstract

Familial hypercholesterolemia is a genetic disorder caused by mutations in the low-density lipoprotein receptor gene (LDLR) and the current treatment still focuses on symptom management. The aim of this study was to develop a lipid nanoparticle (LNP)-based delivery system for the CRISPR/Cas9 component in correcting LDLR gene mutations. LNPs were prepared using an ultrasonic-solvent emulsification technique by varying the surfactant: oil ratio (SOR), homogenization speed and time, and sonication time. Next, the LNP surface was modified by adding DSPE-PEG2000-NH2 and polyethyleneimine. The next stage is to design the single guide RNA (sgRNA) and Donor DNA wildtype (Donor DNA wt). This genetic material was complexed with LNP and then transfected into Hepa1-6 LDLR mt cells, an in vitro representation of cells suffering from familial hypercholesterolemia. This optimization process produced LNPs with a particle size of 118.6±0.8 nm and a polydispersity index of 0.34±0.03. The LNP surface modification resulted in a zeta potential of +7.5 mV. A transmission electron microscope (TEM) analysis howed spherical morphology with size distribution following a regular pattern. LNP cell viability tests showed good biocompatibility at concentrations <15 mM with a half-maximal inhibitory concentration (IC50) value of 27.7 mM. The dominant cellular uptake mechanism of LNP was through the clathrin-mediated endocytosis (CME) pathway. The Hepa1-6 LDLR mt cell model was successfully produced with the transfecting agent Lipofectamine 3000 by homology-directed repair (HDR) mechanism. The LNP-genetic material complex with a ratio of sgRNA:Cas9:Donor DNA wt (1:1:0.04) showed an increase in LDLR gene expression of 3.3±0.2 times and LDLR protein levels reached 12.95±0.25 ng/mL on day 4 after transfection. The results of this study indicate that the developed LNP-based delivery system has the potential for gene therapy applications in familial hypercholesterolemia.
Co-Authors - Satrialdi Abdu Ravi Zakaria Agus Supriyono Ardiyan Harimawan Ardiyan Harimawan Asyarie, Sukmadjaja Audia Triani Olii, Audia Triani CATUR RIANI Dianika Lestari Dianika Lestari Dianika Lestari DOLIH GOZALI Dolih Gozali Dwi Rokhmat Setiawan H. Harapan Hanum, Latifa F. Hidetaka Akita Hideyoshi Harashima I Gusti Ngurah Jemmy Anton Prasetia Khalisa Putri Aqilah Khalisa Putri Aqilah Kosasih Kosasih Kurniati, Neng F. Maria Immaculata Iwo Melia Laniwati Mohd. Andalas Muhamad Insanu Muhammad Ichsan Nafi'ah, Rahma Nafi'ah, Rahma Natalia C. Pedroza Nirmalayanti, Ni LPKV. Nur Mahdi Olii Audia Triani Pamudji, Jessie Sofia Pamudji, Jessie Sofia Pamudji, Jessie Sofia Permana, Benny Permana, Zuliar Ruth Debora Salsafia Putri Salsafia Putri Sasanti Tarini Darijanto, Sasanti Tarini Satrialdi, - Saurabh Laddha Shelly Shelly Sukmadjaja Asyarie Sutiswa, Shandra Isasi Wahono Sumaryono Xeliem, Jovinka N. YEYET CAHYATI Yulius Evan Christian Zefrina, Normalita F.