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生物药剂学分类系统(BCS)IV类药物纳米颗粒:提高其治疗指数的巨大飞跃。

Bio Pharmaceutics Classification System (BCS) Class IV Drug Nanoparticles: Quantum Leap to Improve Their Therapeutic Index.

作者信息

Kumar Sachin, Kaur Ramneek, Rajput Rashi, Singh Manisha

机构信息

Department of Biotechnology, Jaypee Institute of Information Technology Noida 201307, India.

出版信息

Adv Pharm Bull. 2018 Nov;8(4):617-625. doi: 10.15171/apb.2018.070. Epub 2018 Nov 29.

DOI:10.15171/apb.2018.070
PMID:30607334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6311639/
Abstract

Biopharmaceutics classification system (BCS) class IV compounds, exhibits least oral bioavailability, low solubility and intestinal permeability among all pharmaceutical classes of drugs. Thus, these drugs need more compatible and efficient delivery system. Since, their solubility in various medium, remains a limitation so, polymeric nano coacervates based drug loading with modified approach for them may prove to be a solution ahead. Therefore, in present study Chitosan is opted for encapsulating the BCS class IV drug (Hydrochlorothiazide) to attain better stability, enhanced permeability and lower toxicity. For this study, Hydrochlorothiazide (HCTZ) was opted for formulating chitosan based nano-coacervate system. Optimized HCTZ nanocoacervates exhibited the average particle size of 91.39 ± 0.75 nm with Poly-dispersity index score of 0.159 ± 0.01, indicating homogeneity of colloidal solution. Zeta potential and encapsulation efficiency of HCTZ nanocoacervates were recorded as -18.9 ± 0.8 mV and 76.69 ± 0.82 % respectively. Further, from TEM and SEM evaluation the average particle size for the same were found in conformity (35-50 nm), with almost spherical morphology. Also, the EDX (Electron Dispersive X-ray) spectrometry and FT - IR analysis of optimized formulation indicated the balanced chemical composition and interaction between the polymeric molecules. The HCTZ nano coacervates showed the linear diffusion profile through the dialysis membrane. We can conclude from the present study that the optimized HCTZ nano coacervates may prove to be a suitable potential option for effective delivery of BCS class IV drugs.

摘要

生物药剂学分类系统(BCS)IV类化合物在所有药物类别中口服生物利用度最低,溶解度和肠道渗透性也较低。因此,这些药物需要更兼容且高效的递送系统。由于它们在各种介质中的溶解度仍然是一个限制因素,所以基于聚合物纳米凝聚物的药物负载及其改进方法可能是一个可行的解决方案。因此,在本研究中选择壳聚糖来包封BCS IV类药物(氢氯噻嗪),以获得更好的稳定性、增强的渗透性和更低的毒性。在本研究中,选择氢氯噻嗪(HCTZ)来制备基于壳聚糖的纳米凝聚物系统。优化后的HCTZ纳米凝聚物的平均粒径为91.39±0.75nm,多分散指数评分为0.15​​9±0.01,表明胶体溶液具有均一性。HCTZ纳米凝聚物的zeta电位和包封率分别记录为-18.9±0.8mV和76.69±0.82%。此外,通过TEM和SEM评估发现其平均粒径一致(35-50nm),形态几乎呈球形。优化制剂的EDX(电子能谱)光谱和FT-IR分析表明聚合物分子之间具有平衡的化学成分和相互作用。HCTZ纳米凝聚物通过透析膜呈现线性扩散曲线。我们可以从本研究得出结论,优化后的HCTZ纳米凝聚物可能是有效递送BCS IV类药物的合适潜在选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/ff82fea76519/apb-8-617-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/598ebb805ab1/apb-8-617-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/e50b61bc32aa/apb-8-617-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/1e021dc5ab48/apb-8-617-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/2d0d236ed150/apb-8-617-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/6527255a2349/apb-8-617-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/32f9256b7fa7/apb-8-617-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/ff82fea76519/apb-8-617-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/598ebb805ab1/apb-8-617-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/ca2114b92894/apb-8-617-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/08895109bdd0/apb-8-617-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/e50b61bc32aa/apb-8-617-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/1e021dc5ab48/apb-8-617-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/2d0d236ed150/apb-8-617-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/6527255a2349/apb-8-617-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/32f9256b7fa7/apb-8-617-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ee/6311639/ff82fea76519/apb-8-617-g009.jpg

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