Posterior segment eye disease is a leading cause of irreversible vision impairment and blindness. As the unique organ for vision, eyes are protected by various protective barriers. The existence of physiological barriers and elimination mechanisms makes it challenging to treat the posterior segment eye diseases. To achieve efficient drug delivery to the posterior segment of eyes, different drug delivery systems have been proposed. Due to their abilities to enhance ocular tissue permeability, make controlled drug release and target retina, nanocarriers, such as lipid nanoparticles, liposomes and polymeric nanomicelles, have been widely studied for posterior segment drug delivery. However, clinical applications of nanocarrier mediated drug delivery systems as non-invasive ocular drops is still not ready. The delivery of nanocarrier-mediated drug for posterior segment disease still faces the choice of being more effective or more invasive for long-term treatment. Therefore, it is necessary to have a clear understanding of the barriers and the routes of ocular drug delivery while developing the delivery systems. In this review, types of ocular barriers and drug administration routes are categorised in a more intuitive way. Recent advances in nanocarrier mediated drug delivery systems with focus on posterior segment are reviewed with illustrative examples.

Background: Glioblastoma is a lethal neoplasm with few effective therapy options. As a mainstay in the current treatment of glioma at present, chemotherapeutic agents usually show inadequate therapeutic efficiency due to their low blood brain barrier traversal and brain targeting, together with tumor multidrug resistance. Novel treatment strategies are thus urgently needed to improve chemotherapy outcomes. Results: Here, we report that nanomedicines developed by functionalizing the neurotropic rabies virus-derived polypeptide, RVG, and loading reduction-sensitive nanomicelles (polymer and doxorubicin) enable a highly specific and efficacious drug accumulation in the brain. Interestingly, curcumin serves as the hydrophobic core of the polymer, while suppressing the major efflux proteins in doxorubicin-resistant glioma cells. Studies on doxorubicin-resistant rat glioma cells demonstrate that the RVG-modified micelles exhibit superior cell entry and antitumor activity. In vivo research further showed that RVG modified nanomicelles significantly enhanced brain accumulation and tumor inhibition rate in mice, leading to a higher survival rate with negligible systemic toxicity. Moreover, effective suppression of recurrence and pulmonary metastatic nodules were also determined after the RVG-modified nanomicelles treatment. Conclusions: The potential of RVG-modified nanomicelles for glioma was demonstrated. Brain accumulation was markedly enhanced after intravenous administration. This unique drug delivery nanoplatform to the brain provides a novel and powerful therapeutic strategy for the treatment of central nervous system disorders including glioma. Graphic

BACKGROUND:This study aimed to prepare doxorubicin- and tetrahydrocurcumin-loaded and transferrin-modified PEG-PLGA nanoparticles (Tf-NPs-DOX-THC) for enhanced and synergistic chemoradiotherapy. MATERIAL AND METHODS:Tf-NPs-DOX-THC were prepared via t...

Heat shock protein 90 (HSP90) is overexpressed in numerous cancers, promotes the maturation of numerous oncoproteins and facilitates cancer cell growth. Certain HSP90 inhibitors have entered clinical trials. Although less than satisfactory clinical effects or insurmountable toxicity have compelled these trials to be terminated or postponed, these results of preclinical and clinical studies demonstrated that the prospects of targeting therapeutic strategies involving HSP90 inhibitors deserve enough attention. Nanoparticulate-based drug delivery systems have been generally supposed as one of the most promising formulations especially for targeting strategies. However, so far, no active targeting nano-formulations have succeeded in clinical translation, mainly due to complicated preparation, complex formulations leading to difficult industrialization, incomplete biocompatibility or nontoxicity. In this study, HSP90 and CD44-targeted A6 peptide functionalized biomimetic nanoparticles (A6-NP) was designed and various degrees of A6-modification on nanoparticles were fabricated to evaluate targeting ability and anticancer efficiency. With no excipients, the hydrophobic HSP90 inhibitor G2111 and A6-conjugated human serum albumin could self-assemble into nanoparticles with a uniform particle size of approximately 200 nm, easy fabrication, well biocompatibility and avoidance of hepatotoxicity. Besides, G2111 encapsulated in A6-NP was only released less than 5% in 12 h, which may avoid off-target cell toxicity before entering into cancer cells. A6 peptide modification could significantly enhance uptake within a short time. Moreover, A6-NP continues to exert the broad anticancer spectrum of Hsp90 inhibitors and displays remarkable targeting ability and anticancer efficacy both in hematological malignancies and solid tumors (with colon tumors as the model cancer) both in vitro and in vivo. Overall, A6-NP, as a simple, biomimetic and active dual-targeting (CD44 and HSP90) nanomedicine, displays high potential for clinical translation.

The development of a redox-sensitive curcumin conjugated chitosan oligosaccharide nanocarrier for the efficient delivery of docetaxel to glioma cells Chunxi Liu, Yuan Gao, Lixia Zhao, Rui Wang, Fei Xie, Guangxi Zhai, Anchang Liu