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首页> 外文学位 >Development of a self-nanoemulsifying drug delivery system for oral delivery of beta-lactamase.
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Development of a self-nanoemulsifying drug delivery system for oral delivery of beta-lactamase.

机译：开发了用于口服β-内酰胺酶的自纳米乳化药物递送系统。

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摘要

The objective of the study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to deliver protein drugs orally. beta-lactamase (BLM), a hydrophilic protein of 29K Dalton, was loaded into a lipophilic SNEDDS (consist of an oil, a surfactant and a co-surfactant) by preparing a solid dispersion of BLM using a phospholipid and then load this dispersion into SNEDDS. A 2^3 full factorial with 4 center/pure error points experimentaldesign was adopted to develop SNEDDS prototypes with different excipients. Thirty three SNEDDS protoypes obtained were evaluated for loading of BLM-phospholipid solid dispersion into it. Out of those 33, sixteen successful BLM-loaded SNEDDS were obtained. The loading capacity was in the range of 1927.8 +/- 1.5 to 2066.4 +/- 1.3 mU BLM/1g of SNEDDS. The efficacy of these 16 BLM-loaded SNEDDS to deliver BLM was studied with MDCK cell monolayers in-vitro. BLM-loaded SNEDDS formula (NE-12-7) of 49.89% Lauroglycol FCC, 33.21% Cremophor EL, 16.59% Transcutol HP, 0.248% hydrogenated phosphatidyl choline (soy) and 0.062% BLM resulted in maximum in-vitro transport rate and then was further studied in oral pharmacokinetic studies in rats. The BLM-loaded SNEDDS (NE-12-7) exhibited good stability and upon dilution with aqueous media resulted in nanoemulsion with droplet size less than 50 nm. The permeability of BLM in the SNEDDS was 40-fold higher than that by the solution form across MDCK monolayer. In-vivo PK data after oral administration demonstrated that the SNEDDS significantly (P0.01) enhanced the bioavailability (2.5 folds), Cmax (2.7 folds) and Mean Resident Time (MRT, 1.3 folds) compared to the free solution. The relative oral bioavailability of BLM when delivered by SNEDDS and by free solution was 6.3 +/- 0.5% and 2.4 +/- 1.0%, respectively. The C max was 1.90 +/- 0.09 mU/ml and MRT was 12.12 +/- 4.97 hours for the SNEDDS. Thus, SNEDDS could significantly increase the transport of BLM across cell monolayer in-vitro, and enhance the oral absorption in rats. SNEDDS system may be a potential system for oral delivery of protein drugs.
机译：该研究的目的是开发一种自纳米乳化药物递送系统（SNEDDS），以口服蛋白质药物。通过使用磷脂制备BLM的固体分散体，将29K道尔顿的亲水蛋白β-内酰胺酶（BLM）加载到亲脂性SNEDDS（由油，表面活性剂和助表面活性剂组成）中，然后将该分散体加载到SNEDDS。采用具有2个中心/纯净误差点的2 ^ 3全阶乘实验设计来开发具有不同赋形剂的SNEDDS原型。评估获得的33个SNEDDS原型将BLM-磷脂固体分散体的负载量。在这33个中，获得了16个成功加载BLM的SNEDDS。装载量在SNEDDS的1927.8 +/- 1.5至2066.4 +/- 1.3 mU BLM / 1g范围内。用MDCK细胞单层体外研究了这16种BLM负载的SNEDDS递送BLM的功效。载有BLM的SNEDDS配方（NE-12-7）分别为49.89％月桂醇FCC，33.21％Cremophor EL，16.59％Transcutol HP，0.248％氢化磷脂酰胆碱（大豆）和0.062％BLM导致了最大的体外转运率，然后在大鼠的口服药代动力学研究中进一步进行了研究。载有BLM的SNEDDS（NE-12-7）表现出良好的稳定性，并在用水性介质稀释后产生液滴尺寸小于50 nm的纳米乳液。 SNEDDS中BLM的渗透率比溶液形式跨MDCK单层的渗透率高40倍。口服给药后的体内PK数据表明，与游离溶液相比，SNEDDS显着（P <0.01）提高了生物利用度（2.5倍），Cmax（2.7倍）和平均住院时间（MRT，1.3倍）。当通过SNEDDS和通过游离溶液递送时，BLM的相对口服生物利用度分别为6.3 +/- 0.5％和2.4 +/- 1.0％。 SNEDDS的C max为1.90 +/- 0.09 mU / ml，MRT为12.12 +/- 4.97小时。因此，SNEDDS可以显着增加BLM在体外跨细胞单层的转运，并增强大鼠的口服吸收。 SNEDDS系统可能是口服蛋白质药物的潜在系统。

著录项

  • 作者

    Venkata Ramana Rao, Sripriya.;

  • 作者单位

    St. John's University (New York), School of Pharmacy.;

  • 授予单位 St. John's University (New York), School of Pharmacy.;
  • 学科 Health Sciences Pharmacology.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 184 p.
  • 总页数 184
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

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