Brain tumor-targeted drug delivery strategies

Despite the application of aggressive surgery,radiotherapy and chemotherapy in clinics,brain tumors are still a difficult health challenge due to their fast development and poor prognosis.Brain tumor-targeted drug delivery systems,which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue,are a promising new approach to brain tumor treatments.Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues,potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery.In this review,we briefly describe the physiological characteristics of brain tumors,including blood–brain/brain tumor barriers,the tumor microenvironment,and tumor stem cells.We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

Inhibition of post-trabeculectomy fibrosis via topically instilled antisense oligonucleotide complexes co-loaded with fluorouracil

Trabeculectomy is the mainstay of surgical glaucoma treatment,while the success rate was unsatistying due to postoperative scarring of the filtering blebs.Clinical countermeasures for scar prevention are intraoperative intervention or repeated subconjunctival injections.Herein,we designed a codelivery system capable of transporting fluorouracil and anti-TGF-β2 oligonucleotide to synergistically inhibit fibroblast proliferation via topical instillation.This co-delivery system was built based on a cationic dendrimer core(PAMAM),which encapsulated fluorouracil within hydrophobic cavity and condensed oligonucleotide with surface amino groups,and was further modified with hyaluronic acid and cell-penetrating peptide penetratin.The co-delivery system was self-assembled into nanoscale complexes with increased cellular uptake and enabled efficient inhibition on proliferation of fibroblast cells.In vivo studies on rabbit trabeculectomy models further confirmed the anti-fibrosis efficiency of the complexes,which prolonged survival time of filtering blebs and maintained their height and extent during wound healing process,exhibiting an equivalent effect on scar prevention compared to intraoperative infiltration with fluorouracil.Qualitative observation by immunohistochemistry staining and quantitative analysis by Western blotting both suggested that TGF-β2 expression was inhibited by the co-delivery complexes.Our study provided a potential approach promising to guarantee success rate of trabeculectomy and prolong survival time of filtering blebs.