Mucoadhesive Cationic Polypeptide Nanogel with Enhanced Penetration for Efficient Intravesical Chemotherapy of Bladder Cancer

Abstract

Initially, chemotherapy is effective for treatment of bladder cancer after transurethral resection of the bladder. However, certain patients progressively become unresponsive after multiple treatment cycles, which results from the rapid and almost complete excretion of clinically used formulations of antineoplastic agents with urinary voiding. Improving the mucoadhesiveness and penetrability of chemotherapeutic drugs are key factors in treatment of advanced bladder cancer. Here, a smart disulfide‐crosslinked polypeptide nanogel of poly(l‐lysine)–poly(l‐phenylalanine‐co‐l‐cystine) (PLL–P(LP‐co‐LC)) is developed to deliver 10‐hydroxycamptothecin (HCPT) for treatment of orthotopic bladder cancer. The positively charged PLL–P(LP‐co‐LC) can significantly prolong the retention period and enhance the tissue permeability of HCPT within the bladder wall of rat. Moreover, the reduction‐responsive polypeptide nanogel (i.e., NG/HCPT) possesses the capability to accurately and rapidly deliver HCPT in bladder cancer cells. NG/HCPT can significantly inhibit proliferation of human bladder cancer 5637 cells in vitro and enhance antitumor activity toward an orthotopic rat bladder cancer model in vivo. This work demonstrates that the smart polypeptide nanogel may function as a promising drug‐delivery system for local chemotherapy of bladder cancer with unprecedented clinical benefits.

Altered Frequency of NK Cells and Treg Cells by Astragalus Polysaccharide Combined with Budesonide in Asthma Model Mice

“…Previous clinical practice has shown that the clinical e ect of montelukast alone as a leukotriene regulator in the treatment of bronchial asthma needs to be further improved. Polysaccharide served as anti-tumor drug has been well studied in various types of tumor cells [7,8]. In the present study, we established a murine asthmatic model and demonstrated that asthma model mice, challenged with APS and budesonide, exhibited improved airway hyper-responsiveness.…”

Cell Membrane-Camouflaged Nanocarriers for Cancer Diagnostic and Therapeutic

“…Furthermore, many chemotherapeutic drugs are hydrophobic, which can lead to poor absorption and bioavailability. New chemotherapeutics and existing chemotherapeutics with new formulations have recently been developed to address these limitations (Qi et al, 2017;Guo et al, 2018). Application of nanomaterials as chemotherapeutic DDSs has also been studied frequently.…”

Nanogel Functionalization: A Versatile Approach To Meet the Challenges of Drug and Gene Delivery

“…Review in vivo for neat nanogels, 23,192,193 and they should be done also for the functionalized ones and then validated in humans. Indeed, current delivery systems could find problems like quick clearance by the immune system and low selectivity and cell targeting, together with difficulty in crossing biological barriers.…”