转移性乳腺癌
聚乙烯醇
乳腺癌
药代动力学
药理学
医学
化学
癌症
内科学
有机化学
作者
Madhu Sharma,Naresh Mittapelly,Venkatesh Teja Banala,Sandeep Urandur,Shalini Gautam,Disha Marwaha,Nikhil Rai,Neha Singh,Ashutosh Gupta,Kalyan Mitra,Prabhat Ranjan Mishra
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2022-01-03
卷期号:23 (3): 661-675
被引量:22
标识
DOI:10.1021/acs.biomac.1c01076
摘要
HR+/HER2– metastatic breast cancer (MBC) is one of the most common and life-threatening conditions diagnosed in women. The endocrine therapy using an orally active CDK4/6 inhibitor, ribociclib (RB), is the most intriguing approach for treating HR+/HER2– MBC. However, the repeated three to six cycles of multiple dosing and non-targeted distribution of RB led to severe neutropenia; hepatobiliary, gastrointestinal, and renal toxicities, and QT interval prolongation. Here, a novel organic solvent-free HA–PVA–PVP (hyaluronic acid–polyvinyl alcohol–polyvinyl pyrrolidone) composed of a microneedle (MN) array is formulated to deliver RB, integrated with amphiphilic conjugated polymer (HA–GMS)-anchored ultradeformable transfersomes. This unique MN array efficiently crafts microchannels in the skin, allowing HA-RB-Ts to internalize into the tumor cells through lymphatic and systemic absorption and interact with CD44 both spatially and temporally with an amplification of drug release time up to 6-folds. The pharmacokinetic and tissue distribution studies portray drug concentrations within the therapeutic window as long as 48 h, facilitating thrice-a-week frequency with the lower dose, and rule out severe toxicities, with a significant reduction in 8.3-fold RB concentration in vital organs that ultimately enhances the survival rate. Thus, the novel MN system pursues a unique embeddable feature and offers an effective, self-administrable, biodegradable, and chronic treatment option for patients requiring long-term cancer treatments.
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