[논문]약물 전달 시스템 적용을 위한 셀룰로오스 나노크리스탈(CNCs) 강화 Poly(vinyl alcohol) 기반 하이드로겔의 제조 및 특성

CHO, Hyejung; YOO, Won-Jae; AHN, Jinsoo; CHUN, Sang-Jin; LEE, Sun-Young; GWON, Jaegyoung

doi:10.5658/wood.2020.48.4.431

약물 전달 시스템 적용을 위한 셀룰로오스 나노크리스탈(CNCs) 강화 Poly(vinyl alcohol) 기반 하이드로겔의 제조 및 특성
Preparation and Characterization of Cellulose Nanocrystals Reinforced Poly (vinyl alcohol) Based Hydrogels for Drug Delivery System 원문보기

목재공학 = Journal of the Korean wood science and technology, v.48 no.4, 2020년, pp.431 - 449

CHO, Hyejung (Division of Wood Chemistry, Department of forest Products, National Institute of Forest Science) , YOO, Won-Jae (Division of Wood Chemistry, Department of forest Products, National Institute of Forest Science) , AHN, Jinsoo (Division of Wood Chemistry, Department of forest Products, National Institute of Forest Science) , CHUN, Sang-Jin (Division of Wood Utilization, Department of forest Products, National Institute of Forest Science) , LEE, Sun-Young (Forest Biomaterials Research Center, National Institute of Forest Science) , GWON, Jaegyoung (Division of Wood Chemistry, Department of forest Products, National Institute of Forest Science)

초록
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기존 연질 구조의 하이드로겔은 낮은 기계적 강도로 인하여 생의학 분야에서 응용이 제한된다. 본 연구에서는 이러한 단점을 극복하기 위해서 폴리비닐알코올(PVA: poly(vinyl alcohol))기반 하이드로겔에 셀룰로오스 나노크리스탈(CNCs)을 첨가하여 CNCs가 기계적 특성 및 약물전달 효율에 미치는 영향을 확인하였다. 제조된 하이드로겔은 FT-IR 분석으로 아세탈 및 알데히드 결합으로 가교결합된 망상구조(semi-IPN: semi-interpenetrating polymer network)로 합성된 것이 확인되었다. CNCs 함량이 증가될수록 수분 흡수 및 팽윤도가 감소했으며, 점탄성은 증가하였다. 또한 CNCs의 첨가는 약물 로딩량의 증가와 약물 방출량의 지속성을 향상시켰다. 이러한 결과는 CNCs를 하이드로겔에 첨가하는 것이 하이드로겔의 약물전달 효율성 및 기계적 특성을 개선시키는 좋은 대안이 될 수 있음을 보여주었다.

Abstract ▼ AI-Helper

Structural property of most hydrogels is soft, resulting in low mechanical performance that limits their usage in the biomedical applications. For overcoming the drawback, cellulose nanocrystals (CNCs) were adopted in this study. Effects of CNCs on characteristics and drug delivery performance of poly (vinyl alcohol) based hydrogels were explored. FT-IR results showed that the fabricated hydrogels had semi-IPN (semi-interpenetrating polymer network) by formation of acetal and aldehyde bridge. Water absorption and swelling ratio decreased with increasing CNCs content, and the hydrogels with CNCs showed better viscoelastic performance than the without CNCs. Also, CNCs mostly improved the ability of the hydrogel to absorb the drug and the sustainability of the drug release. These results demonstrated that incorporating CNCs into the hydrogel systems can be a good alternative to improve drug delivery performance and mechanical property of the hydrogels.

주제어

표/그림 (12)

그림 Fig. 1. Visual appearance of prepared PVA based hydrogels incorporated with CNCs.
표 Table 1. Component of PVA/CNCs/GA hydrogels
표 Table 2. Analytical condition of HPLC
그림 Fig. 3. SEM images of the PVA/CNCs/GA hydrogels (a) CNC0 (b) CNC10 (c) CNC20 with magnitude x 300.
그림 Fig. 2. FTIR spectra of the PVA/varied CNCs content/ GA hydrogels with/without drugs.
그림 Fig. 4. Water content and Swelling ratio of the PVA/CNCs/GA hydrogels with varied CNCs content.
그림 Fig. 5. Frequency sweep test of storage modulus (G') and loss modulus (G") of the PVA/CNCs/GA hydrogels with varied CNCs content.
그림 Fig. 6. Fitting of a)total loading drugs b)linear plots of Langmuir isotherms and c)linear plots of Freundlich isotherms over PVA/CNCs/GA hydrogels with varied CNCs content and their respective correlation coefficients.
그림 Fig. 7. Surface area to pore volume ratio (m²·g^-1/cm³·g^-1) of the PVA/CNCs/GA hydrogel systems with varied CNCs content.
표 Table 3. The Freundlich isotherm constants for the loading drugs
그림 Fig. 8. Fitting of a)cumulative released drugs b)linear plots of pseudo 1^st order model released kinetics and c)linear plots of pseudo 2^nd order model released kinetics over PVA/CNCs/GA hydrogels with varied CNCs content and their respective correlation coefficients.
표 Table 4. The pseudo 1^st order model and pseudo 2^nd order model constants for the released drugs

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제안 방법

CNCs-based PVA hydrogels were prepared, and its physical, chemical and mechanical properties were investigated. Also, salicylic acid as a drug model was applied to investigate the adsorption and release properties of hydrophobic drugs, and the interaction between the drug and the hydrogels was evaluated using various dynamic models.
In this study, CNC was applied to the PVA hydrogel system in which glutaraldehyde (GA) was used as a crosslinking agent, and the adsorption and release behavior of the drug was examined after salicylic acid (SA) was introduced as a drug model. To evaluate the structural properties of the hydrogel, fourier transform infrared (FT-IR) spectroscopy, water content, swelling ratio, specific surface area, scanning electron microscopy (SEM) and viscoelastic properties were analyzed.
To check swelling properties, the hydrogels dried for 12 hours in a chamber at 70 ℃ were immersed in distilled water at 37 ℃. The purpose was to check the swelling ratio according to the weight by time compared to the initial weight. The weight was measured three times to be determined in the error range of ± (0.
To evaluate mechanical properties of hydrogels by CNCs content, CNCs-based PVA hydrogels’ storage modulus and loss modulus were analyzed using parallel and peltier plates with DHR3 rheometer (TA instruments, US).
In this study, CNC was applied to the PVA hydrogel system in which glutaraldehyde (GA) was used as a crosslinking agent, and the adsorption and release behavior of the drug was examined after salicylic acid (SA) was introduced as a drug model. To evaluate the structural properties of the hydrogel, fourier transform infrared (FT-IR) spectroscopy, water content, swelling ratio, specific surface area, scanning electron microscopy (SEM) and viscoelastic properties were analyzed. In addition, Langmuir, Freundlich adsorption model was applied to see interaction between hydrogels and the drug, and Lagergren's pseudo 1^st order model and Ho's pseudo 2^ndorder model were applied for the release behavior.

대상 데이터

1098, Sigma-aldrich), having a molecular weight of 61,000 Da, and glutaraldehyde (GA, Sigma-aldrich) was used as a crosslinking agent. The CNCs used in this study are made from cellulose powder (KC Flock W-50, average size: 45 ㎛) purchased from Nippon Paper Chemicals Co., Ltd. (Tokyo, Japan). And then, by the same method as in the previous study (Gwon et al.

이론/모형

In order to obtain process parameters for applying the drug-loaded hydrogels to the drug system by the impregnation method, the appearance of the hydrogel interface and drug loading were predicted using an adsorption isotherm model. The interfacial reaction between the hydrogels and the drug was observed by using Langmuir isotherm, which is composed of a monolayer on a single interface and mainly shown in chemical bonds, and Freundlich isotherm, where a drug combines on a heterogeneous interface with multilayers by physical adsorption (Cho et.
In this study, the drug loading performance was investigated using Langmuir isotherm and Freundlich isotherm as adsorption isotherm models. And the results are shown in Fig.

성능/효과

0001. Also, it was calculated to be 0.9956, 0.9975, and 0.9690 by Freundlich isotherm, therefore, it was confirmed that Freundlich isotherm is more suitable for the salicylic acid loading mechanism of CNCs-based PVA hydrogels than Langmuir isotherm. Therefore, the drug ions, with the salicylic acid molecules on the inner interface of the hydrogels, were layered ina multi-molecule layer (Freundlich isotherm) instead of being bound as a mono molecular layer (Langmuir isotherm).
And then, drug loading and release characteristics of the hydrogel prepared using salicylic acid (salicylic acid, ≥99.0%, Sigma-aldrich), one of the hydrophobic low-molecular-weight drugs, were observed.
and 8c; all release data was applied to the pseudo 1^storder model and the pseudo 2^nd order model to evaluate release speed. By comparing r² : correlation coefficient of a trend line, it was confirmed that the pseudo 2^nd order model was more suitable than the pseudo 1^st order model. The reaction speed constant k₂ and h, which means the initial release speed, were calculated for comparative analysis of drug release rate through the the pseudo 2^nd order model and the results were shown in Table 4.
3 shows SEM images that were measured to verify the 3D scaffold network (semi-IPN) of the hydrogels. From these results, it was concluded that PVA, CNCs and GA had a 3D pore structure interconnected by crosslinking between hydroxyl groups, and the size of the pores increased as the content of CNCs increased.
These characteristics of CNCs involved that water content and swelling ratio have decreased, andviscoelasticity has increased as the mechanical properties. In addition, from the analysis of drug loading behavior, Langmuir isotherm and Freundlich isotherm were applied, and it was found that Freundlich isotherm is more suitable than Langmuir isotherm. From this study, it has been loaded ina multi-molecular layer multiplied by physical and chemical bonds inside the hydrogels, not a mono-molecular layer of the drug.
At K_F and n which represent adsorption performance, CNC10 showed higher values than CNC20, confirming that CNC10 was a more favorable condition for drug loading. In conclusion, to increase drug loading amount by improving the mechanical strength on CNCs-based PVA hydrogels, a content of CNCs should be optimized and application of CNC10 is more beneficial.
Also, salicylic acid as a drug model was applied to investigate the adsorption and release properties of hydrophobic drugs, and the interaction between the drug and the hydrogels was evaluated using various dynamic models. The FT-IR results showed that inner PVA hydrogels with GA as a cross-linking-agent formed a 3D scaffold cross-linked network (semi-IPN), and it allowed a strong and dense 3D structure by adding CNCs. These characteristics of CNCs involved that water content and swelling ratio have decreased, andviscoelasticity has increased as the mechanical properties.
When comparing the drug loading performance of the hydrogels to which CNC10 and CNC20 were applied, it was confirmed that the loading efficiency of CNC20 was reduced compared to that of CNC10. It may be explained by a decrease of inner surface area and adsorption mechanism.

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