Mobed-Miremadi Maryam, Nagendra Raki Komarla, Ramachandruni Sujana Lakshmi, Rook Jason James, Keralapura Mallika, Goedert Michel
Department of Biomedical, Chemical and Materials Engineering, San Jose State University, San Jose, CA, 95192-0082, USA.
MSE Biomedical Devices Concentration, San Jose State University, San Jose, CA, USA.
Prog Biomater. 2013 Jan 24;2(1):1. doi: 10.1186/2194-0517-2-1.
Custom-designed wound dressing films of chitosan and alginate have been prepared by a casting/solvent evaporation method for hydrophobic therapeutic agent encapsulation. In this parametric study, the propylene glycol (PG) and calcium chloride (CaCl) concentrations were varied for chitosan and alginate films, respectively. Mechanical and chemical inter-related responses under observations included thickness (th), elasticity (E), tensile strength (TS), sorption ability (S%) and kinetics of in-vitro drug release, specifically in terms of membrane time to burst (t ) and duration of release (t ). As shown by results of a one tailed t-test significance testing at the 95% confidence interval (α = 0.05), alginate films were significantly more elastic (p = 0.003), thinner (p = 0.004) and more susceptible to osmotic burst (p = 0.011) and characterized by a longer duration of release (p = 0.03). Meanwhile chitosan films exhibited superior moisture permeability (p = 0.006) and sorption characteristics (p = 0.001), indicative of higher hydrophilicity. There were no significant differences in tensile strength (p = 0.324) for alginate and chitosan-based formulations. Preliminary testing was conducted using 0.71 μm in diameter microspheres for modeling film dissolution into Lactated Ringer's solution. Experimental release profiles were modeled for each film from which the average release from alginate films (M = 81%) was estimated to be twice the percentage associated with chitosan films (M = 42%). The film comprised of 2.5% (w/v) medium MW chitosan/dextran 70 kDa (5:1) was selected for studying the release of 5-Fluorouracil (5-FU) as a model hydrophobic drug. Diffusion coupled with film disintegration is immediate (t = 0) in case of encapsulated 5-FU as compared to the control film encapsulating microspheres characterized by t = 70 min ± 7 min. This shift in release profile and the ability to modulate the timing of membrane burst can be attributed to the approximate ratio (1: 505) in molecular size between drug and microsphere. This hypothesis has been validated by the film pore size measured to be 430 nm ± 88 nm using atomic force microscopy.
通过流延/溶剂蒸发法制备了定制设计的壳聚糖和海藻酸盐伤口敷料薄膜,用于封装疏水性治疗剂。在这项参数研究中,分别改变了壳聚糖和海藻酸盐薄膜中丙二醇(PG)和氯化钙(CaCl)的浓度。观察到的机械和化学相关响应包括厚度(th)、弹性(E)、拉伸强度(TS)、吸附能力(S%)和体外药物释放动力学,具体涉及膜破裂时间(t )和释放持续时间(t )。如在95%置信区间(α = 0.05)进行的单尾t检验显著性测试结果所示,海藻酸盐薄膜弹性显著更高(p = 0.003)、更薄(p = 0.004),更容易发生渗透破裂(p = 0.011),且释放持续时间更长(p = 0.03)。同时,壳聚糖薄膜表现出优异的透湿性(p = 0.006)和吸附特性(p = 0.001),表明亲水性更高。基于海藻酸盐和壳聚糖的制剂在拉伸强度方面没有显著差异(p = 0.324)。使用直径为0.71μm的微球进行初步测试,以模拟薄膜在乳酸林格氏溶液中的溶解情况。对每种薄膜的实验释放曲线进行建模,据此估计海藻酸盐薄膜的平均释放率(M = 81%)是壳聚糖薄膜(M = 42%)的两倍。选择由2.5%(w/v)中等分子量壳聚糖/70 kDa葡聚糖(5:1)组成的薄膜来研究作为模型疏水性药物的5-氟尿嘧啶(5-FU)的释放。与封装微球的对照薄膜(其t = 70分钟±7分钟)相比,封装5-FU的情况下,扩散与薄膜崩解是即时的(t = 0)。释放曲线的这种变化以及调节膜破裂时间的能力可归因于药物与微球之间分子大小的近似比例(1:505)。使用原子力显微镜测得薄膜孔径为430nm±88nm,这一假设得到了验证。