Design and controlled release of peptide drug-loaded fattigated nanoparticles for long-acting delivery
- 주제(키워드) pasireotide , long-term controlled release , fattigation platform , fatty acid substitutions , initial burst release , calcium ion-triggering nanoaggregates
- 주제(DDC) 615.1
- 발행기관 아주대학교 일반대학원
- 지도교수 Beom-Jin Lee
- 발행년도 2025
- 학위수여년월 2025. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000034352
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
The aim of this research was to investigate the long-term controlled release of peptide-loaded fattigated albumin nanoparticles via calcium ion-triggering nanoaggregation with minimal initial burst release. Fattigated albumin nanoparticles were prepared via sonication by the self-assembly of human serum albumin (HSA)- oleic acid conjugates (AOC) with three different substitution ratios of oleic acid (OA) to modulate hydrophobicity. Then, pasireotide pamoate (PAS) as a model peptide was encapsulated into the hydrophobic core of albumin-oleic acid nanoparticles (PAS-AONs). The critical micelle concentration (CMC) decreased as OA substitution ratio increased. The loading efficiency of PAS increased owing to the strong hydrophobic-hydrophobic interactions between PAS and the hydrophobic block in the AONs. The release rate was also delayed, whereas the initial burst release was minimized, as the hydrophobicity of AOC increased. Interestingly, calcium ions triggered the formation of nanoaggregates of negatively charged PAS- AONs via electrostatic interactions, resulting in a further decrease in the release rate for one month via a reduced surface area while minimizing the initial burst release in a calcium ion concentration-dependent manner. The modulation of OA substitutions and calcium ion concentration of AONs could provide the potential for long-term delivery of peptide drugs while minimizing the initial huge burst release and controlling the release rate.
more목차
1. Introduction 1
2. Materials and Methods 4
2.1. Materials 4
2.2. Synthesis of human serum albumin-oleic acid conjugates (AOCs) 4
2.3. Preparation of AON and loading of PAS into AONs (PAS-AONs) 5
2.3.1. Self-assembled AONs and loading PAS into the AON (PAS-AON) 5
2.3.2. Encapsulation efficiency (EE) and loading capacity (LC) 6
2.4. Characterization of AOCs and PAS-AONs 7
2.4.1. Fourier transform-infrared (FT-IR) spectroscopy 7
2.4.2. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy 7
2.4.3. Degree of AOC substitution based on oleic acid molar ratio 7
2.4.4. Dynamic light scattering (DLS) measurement 8
2.4.5. Field emission scanning electron microscopy (FE-SEM) 8
2.5. Critical micelle concentration of AOCs 8
2.6. Physical stability of PAS-AONs 9
2.7. Aggregation of PAS-AON100 with calcium cations 9
2.8. Drug release test in vitro 9
2.9. Quantitative analysis of pasireotide by HPLC-UV 10
3. Results and discussions 11
3.1. Synthesis and characterization of AOCs 11
3.2. Physicochemical characteristics of PAS-AONs 14
3.2.1. Physicochemical properties of PAS-AONs 14
3.2.2. Critical micelle concentration of AOCs 18
3.2.3. Physical stability of PAS-AONs 20
3.3. In vitro release test of PAS-AONs 22
3.4. Aggregation of PAS-AON100 with calcium cation 24
3.5. In vitro release test of PAS-AON100 aggregation 27
4. Conclusions 30
5. References 31
Supplementary Data 36
국문초록 42
