A novel polymeric mixed micelle composed of Pluronic F127 and D-α-tocopheryl polyethylene glycol succinate (TPGS) was developed to improve the delivery of fluorescent dyes and protein across the blood brain barrier (BBB). Rhodamine 123 (Rho123) and DiR loaded mixed micelles, composed of Pluronic F127 and TPGS with proportion of 4:1 (FT), were prepared by thin-film hydration, and β-galactosidase (β-Gal) loaded FT mixed micelles were prepared by self-assembly. The brain-targeted capability of FT mixed micelles were evaluated both in vitro and in vivo. The FT mixed micelles showed that a average particle size of 20.03 nm, and a low CMC of 0.0031% in water. The in vitro release of Rho123 from Rho123 loaded FT mixed micelles (FT/Rho123) presented a sustained-release property. FT/Rho123 also showed higher efficiency for the accumulation in brain capillary endothelial cells (BCECs) and brain tissues. β-Gal, a model protein, was also delivered and accumulated efficiently in the brain by spontaneous loading in the FT mixed micelles. Therefore, the results indicated that F127/TPGS mixed micelles may be considered as an effective nanocarrier for the brain-targeted delivery of diagnostic and therapeutic drugs.
For
melanoma with high lethality and metastasis rate, traditional
therapy has limited effects; local photothermal therapy (PTT) synergetic with immune therapy
for cancer treatment can perhaps improve the situation. However, because
of the natural existence of the tumor matrix barrier, the penetration
depth of drugs and immune cells often dampens the efficacy of cancer
treatment. Herein, we report an innovative synergetic PTT and immune
therapy through dissolving microneedles for the codelivery of the
hyaluronidase-modified semiconductor polymer nanoparticles containing
poly(cyclopentadithiophene-alt-benzothiadiazole)
and immune adjuvant polyinosinic–polycytidylic acid (PIC).
Benefiting from the dissolution of an extracellular matrix of hyaluronidase,
the semiconductor polymer nanoparticles and PIC penetrate the tumor
deeply, under synergetic therapy with PTT, activating the immune cells
and enhancing the T-cell immune response for inhibition of tumor growth
and metastasis. This study provides a promising platform for effective
melanoma treatment and a novel strategy to overcome the stromal barrier.
Quasi-2D
perovskites have attracted extensive attention due to
their extraordinary stability compared to their 3D counterparts. Presently,
the bottleneck in quasi-2D perovskite solar cells is their relatively
low efficiency. The intrinsic interior carrier transport in the perovskite
layer consisting of disorderly oriented phases and inadequate optimization
of interfacial carrier transfer have greatly limited the overall device
performance. A comprehensive study on effective phase manipulation
in the BA2MA4Pb5I16 (n = 5) quasi-2D perovskites is presented to pursue optimal
efficiency. With the assistance of the solvent DMSO in a constant
thermal-annealing spin-coating (CTAS) process, the crystalline growth
process in the quasi-2D perovskite film is effectively manipulated
and delicate energy band alignment by eliminating the n ≤ 2 phases at the bottom surface has been successfully achieved.
Consequently, a significant improvement of carrier transport in the
perovskite layer and photogenerated hole extraction at the interface
has been accomplished. The champion device exhibited a boosted PCE
of 17.66%.
Background
P-glycoprotein (P-gp) mediated drug efflux across the blood–brain barrier (BBB) is an important mechanism underlying poor brain penetration of certain antiepileptic drugs (AEDs). Nanomaterials, as drug carriers, can overcome P-gp activity and improve the targeted delivery of AEDs. However, their applications in the delivery of AEDs have not been adequately investigated. The objective of this study was to develop a nano-scale delivery system to improve the solubility and brain penetration of the antiepileptic drug lamotrigine (LTG).
Methods
LTG-loaded Pluronic
®
P123 (P123) polymeric micelles (P123/LTG) were prepared by thin-film hydration, and brain penetration capability of the nanocarrier was evaluated.
Results
The mean encapsulating efficiency for the optimized formulation was 98.07%; drug-loading was 5.63%, and particle size was 18.73 nm. The solubility of LTG in P123/LTG can increase to 2.17 mg/mL, making it available as a solution. The in vitro release of LTG from P123LTG presented a sustained-release property. Compared with free LTG, the LTG-incorporated micelles accumulated more in the brain at 0.5, 1, and 4 hours after intravenous administration in rats. Pretreatment with systemic verapamil increased the rapid brain penetration of free LTG but not P123/LTG. Incorporating another P-gp substrate (Rhodamine 123) into P123 micelles also showed higher efficiency in penetrating the BBB in vitro and in vivo.
Conclusion
These results indicated that P123 micelles have the potential to overcome the activity of P-gp expressed on the BBB and therefore show potential for the targeted delivery of AEDs. Future studies are necessary to further evaluate the appropriateness of the nanocarrier to enhance the efficacy of AEDs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.