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  • Simon Hoover heeft een update geplaatst 20 uren, 1 minuut geleden

    Anti-PEG antibodies have been witnessed in patients and experimental animals, accelerating the blood clearance (termed ABC phenomenon) of PEGylated nanomedicines by activating complement after absorption on the nano-surface. The ABC phenomenon presents an obstacle to the clinical translation of PEGylated nanomedicines. Herein, an anti-PEG single-chain variable fragment (PEG-scFv) that possesses a low molecule weight (30 kDa) and high PEG binding affinity was exploited to ameliorate the ABC phenomenon of PEGylated liposomes (sLip). Pre-deposition of PEG-scFv on the surface of sLip was incompetent to activate complement due to the lack of Fc chains, exhibiting negligible influence on in vivo performance of sLip in naïve rats (without anti-PEG antibodies). However, PEG-scFv effectively competed the binding of anti-PEG IgM in rats that were pre-stimulated with low dose of sLip, thus ameliorated the ABC phenomenon of sLip. PEG- scFv was also effective to inhibit the binding of anti-PEG antibodies with sLip in human plasma and the consequent complement activation, presenting a promising tool to improve the performance of PEGylated nanomedicines and to mitigate individual difference occurred by the varying levels of anti-PEG antibodies in the clinic. The application of anti-PEG scFv paves a new avenue for the development of nanocarriers to achieve precise medication.Existing oral or injectable antipsychotic drug delivery strategies typically demonstrate low bioavailability to targeted brain regions, incentivizing the development of alternative delivery strategies. Delivery via the nasal cavity circumvents multiple barriers for reaching the brain but requires drug delivery vehicles with very specific properties to be effective. Herein, we report in situ-gelling and degradable bulk nanoparticle network hydrogels consisting of oxidized starch nanoparticles (SNPs) and carboxymethyl chitosan (CMCh) that enable intranasal delivery via spray, high nasal mucosal retention, and functional controlled release of the peptide drug PAOPA, a positive allosteric modulator of dopamine D2 receptor. PAOPA-loaded SNP-CMCh hydrogels can alleviate negative symptoms like behavioural abnormalities associated with schizophrenia (i.e. decreased social interaction time) for up to 72 h in an MK-801-induced pre-clinical rat model of schizophrenia at a low drug dosage (0.5 mg/kg); in comparison, conventional PAOPA administration via the intraperitoneal route requires twice the PAOPA dose to achieve a therapeutic effect that persists for only a few hours. This strategy offers potential for substantially decreasing re-administration frequencies and overall drug doses (and thus side-effects) of a range of potential antipsychotic drugs via a minimally-invasive administration route.As a photosensitizer with effective photothermal (PTT) and photodynamic (PDT) response, IR780 has been widely explored as promising cancer phototheranostic molecule. However, the systematic administration of IR780 usually suffers from poor water solubility and low photostability, so that it cannot be administrated by parenteral route. Selleck WP1066 In this study, we design a tetrahedral DNA (Td)-based nanosystem to load IR780 (IR780@Td) via electrostatic interaction and π-π stacking. After encapsulation, the water solubility and photostability of IR780 have been greatly improved, and the IR780@Td shows an appropriate nanoformulated size (224 nm) to facilitate hyperthermia-mediated tumor targeting by EPR effect. The nanostructure of Td is proved to be crucial for the proper size and good stability of IR780@Td nanoformulation for in vivo application. The in vitro and ex vivo PTT/PDT efficiencies of IR780 are improved in IR780@Td group. In the tumor-bearing mice, the accumulation of IR780 in tumor site is significantly high in IR780@Td group. Under near-infrared laser irradiation, the intravenous administration of IR780@Td promotes the tumor imaging and enhances anti-tumor effect than IR780 treatment. In summary, the proposed strategy shows promising effect in facilitating intravenous injection of IR780 and enhancing the phototheranostic efficacy for cancer treatment.As a common method for postoperative adjuvant treatments of bladder tumor, chemotherapy encounters low tumor targeting, short tumor retention time and bad bioavailability in clinical applications, which result in unsatisfactory high chemotherapeutical doses, frequent administration and subsequent severe side effects. Herein, we innovatively introduced the enzyme-assisted assembly to construct a bladder tumor-specific transformable peptide prodrug (i.e. HCPT-FF-GFLG-EEYSA). The prodrug targeted bladder tumor through the specific binding capacity of YSA to EphA2 and underwent on-demand structural transformation intracellularly from micelles to fibrils catalyzed by cathepsin B (CtsB), of which EphA2 and CtsB are overexpressed on the outer membrane and in cytoplasm of bladder tumor cells, respectively. Comparing with hydroxycamptothecin (HCPT), the prodrug can prolong the drug retention time and release the active drug in a sustained manner, which in turn decrease the administration frequencies of chemotherapeutics and reduce the side toxicities, etc. This strategy provides an alternative for bladder tumor chemotherapeutics and shows great potential to inhibit the relapse of postoperative tumors.Layered double hydroxides (LDHs), also known as anionic clays or hydrotalcite-like compounds, are a class of nanomaterials that attained great attention as a carrier for drug delivery applications. The lamellar structure of this compound exhibits a high surface-to-volume ratio which enables the intercalation of therapeutic agents and releases them at the target site, thereby reducing the adverse effect. Moreover, the intercalated drug can be released in a sustained manner, and hence the frequency of drug administration can be decreased. The co-precipitation, ion exchange, manual grinding, and sol-gel methods are the most employed for their synthesis. The unique properties like the ease of synthesis, low cost, high biocompatibility, and low toxicity render them suitable for biomedical applications. This review presents the advances in the structure, properties, method of preparation, types, functionalization, and drug delivery applications of LDH. Also, this review provides various new conceptual insights that can form the basis for new research questions related to the drug delivery applications of LDH.

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