B16F10 Cell Membrane-Based Nanovesicles for Melanoma Therapy Are Superior to Hyaluronic Acid-Modified Nanocarriers.

Some cancer cell membrane (CCM)-derived nanovesicles show strong homing effects and are used for targeted cancer therapy. By co-constructing the B16F10 cell membrane with a PEGylated phospholipid membrane, a new nanocarrier with a composite nanocrown structure was developed, which can evade immune recognition and actively target homologous melanoma. The nanocrowns have an encapsulation efficiency of more than 90% for paclitaxel and showed no significant difference (p > 0.05) from the PEGylated phospholipid membrane vesicles. Compared with the hyaluronic acid-modified PEGylated phospholipid membrane vesicles, the biomimetic nanocrowns enhanced the escape of nanovesicles from reticuloendothelial cells in vitro and extended the circulation time in vivo; moreover, the nanocrowns showed superior melanoma-targeted drug delivery capability and improved anticancer effects of paclitaxel as demonstrated by the inhibition of B16F10 cell proliferation and induction of apoptosis by interfering with microtubule formation. In contrast, the modification of hyaluronic acid did not increase the targeting capacity or antitumor effects of the nanocrowns, confirming that the superior targeting capacity was mediated by the exposed homologous CCMs rather than by hyaluronic acid. Our results demonstrate the potential of using biomimetic nanocrowns for active melanoma-targeted therapy.

A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy.

BACKGROUND: A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed. RESULTS: Herein, we designed hyaluronic acid (HA)-hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway. CONCLUSIONS: The multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment.

A novel microemulsion-based isotonic perfusate modulated by Ringer's solution for improved microdialysis recovery of liposoluble substances.

BACKGROUND: Microdialysis is promising technique for dynamic microbiochemical sampling from tissues. However, the application of typical aqueous perfusates to liposoluble substances is limited. In this study, a novel microemulsion (ME)-based isotonic perfusate (RS-ME) was prepared to improve the recovery of liposoluble components using microdialysis probes. RESULTS: Based on pseudo-ternary phase diagrams and comparisons of the ME area, Kolliphor® EL and Transcutol® P were selected as the surfactant and co-surfactant, respectively, with a weight ratio (Km) of 2:1 and ethyl oleate as the oil phase. The ME was mixed with Ringer's solution at a 1:6 ratio (v/v) to obtain the isotonic RS-ME. The droplet size distribution of the ME in RS-ME was 78.3 ± 9.2 nm, with a zeta potential of - 3.5 ± 0.3 mV. By microdialysis perfusion, RS-ME achieved higher recovery rates of the poorly water-soluble compounds evodiamine (EVO) and ruthenium (RUT), i.e., 58.36 ± 0.57% and 49.40 ± 0.57%, respectively, than those of 20% (v/v) PEG 400 Ringer's solution (RS-PEG) and 10% (v/v) ethanol Ringer's solution (RS-EtOH). In vivo microdialysis experiments confirmed that RS-ME captured EVO and RUT molecules around the dialysis membrane more efficiently and exhibited less spreading than RS-PEG and RS-EtOH. CONCLUSIONS: Owing to the nanosized droplets formed by lipid components in the RS-ME and the limited dispersion out of the dialysis membrane, we obtained good biocompatibility and reliable dialysis results, without affecting the tissue microenvironment. As a novel perfusate, RS-ME provides an easy and reliable approach to the microdialysis sampling of fat-soluble components.

Optimizing glycerosome formulations via an orthogonal experimental design to enhance transdermal triptolide delivery.

Triptolide exerts strong anti-inflammatory and immunomodulatory effects; however, its oral administration might be associated with side effects. Transdermal administration can improve the safety of triptolide. In this study, glycerosomes were prepared as the transdermal vehicle to enhance the transdermal delivery of triptolide. With entrapment efficiency and drug loading as dependent variables, the glycerosome formulation was optimized using an orthogonal experimental design. Phospholipid-to-cholesterol and phospholipid-to-triptolide mass ratios of 30:1 and 5:1, respectively and a glycerol concentration of 20 % (V/V) were used in the optimization. The glycerosomes prepared with the optimized formulation showed good stability, with an average particle size of 153.10 ± 2.69 nm, a zeta potential of -45.73 ± 0.60 mV and an entrapment greater than 75 %. Glycerosomes significantly increased the transdermal delivery of triptolide compared to conventional liposomes. As efficient carriers for the transdermal delivery of drugs, glycerosomes can potentially be used as an alternative to oral triptolide administration.

Cholesterol and Phospholipid-free Multilamellar Niosomes Regulate Transdermal Permeation of a Hydrophobic Agent Potentially Administrated for Treating Diseases in Deep Hair Follicles.

We designed cholesterol- and phospholipid-free multilamellar niosomes (MLNs) structured by glyceryl monooleate (GMO) and poloxamer 407 (F127), and evaluated their capacity for transdermal drug delivery. The optimized MLNs had a mean size of 97.88 ± 63.25 nm and an encapsulation efficiency of 82.68% ± 2.14%. The MLNs exhibited a remarkable sustained cargo release, and improved the permeation of the stratum corneum. Compared with the tincture, lower transdermal flux but higher skin deposition of aconitine in vitro were achieved in the MLN group (p < 0.05). Additionally, both water-soluble rhodamine B- and liposoluble coumarin 6-labeled MLNs were found to penetrate deeply into the skin through the hair follicles and could be internalized by fibroblasts Notably, the MLNs possessed greater wettability, and the study focused on delivery to deeper hair follicles and up to the outer hair sheath, which showed advantages for treating diseases of hair follicles, and was potentially superior to the hydrophobic PLGA nanoparticles (diameter: 637.87 ± 22.77 nm) which mainly accumulated in superficial hair follicles. Hair follicles were therefore demonstrated to be an important way to enhance skin permeability, and MLNs are a promising alternative for topical and transdermal drug delivery.

Recent Developments in the Principles, Modification and Application Prospects of Functionalized Ethosomes for Topical Delivery.

Transdermal drug delivery helps to circumvent the first-pass effect of drugs and to avoid drug-induced gastrointestinal tract irritation, compared with oral administration. With the extensive application of ethosomes in transdermal delivery, the shortages of them have been noticed continuously. Due to the high concentration of volatile ethanol in ethosomes, there are problems of drug leakage, system instability, and ethosome-induced skin irritation. Thus, there is a growing interest in the development of new generations of ethosomal systems. Functionalized ethosomes have the advantages of increased stability, improved transdermal performances, an extended prolonged drug release profile and site-specific delivery, due to their functional materials. To comprehensively understand this novel carrier, this review summarizes the properties of functionalized ethosomes, their mechanism through the skin and their modifications with different materials, validating their potential as promising transdermal drug delivery carriers. Although functionalized ethosomes have presented a greater role for enhanced topical delivery, challenges regarding their design and future perspectives are also discussed.

Sodium dodecyl sulfate improved stability and transdermal delivery of salidroside-encapsulated niosomes via effects on zeta potential.

Niosomes are novel carriers that show superior transdermal permeation enhancement but require the addition of charged stabilizers. In this study, niosomes were prepared using Span 40, cholesterol, and sodium dodecyl sulfate (SDS) as stabilizers for transdermal delivery of salidroside. At concentrations of 0.05-0.40% (w/v), SDS significantly increased the zeta potential of the nanovesicles from -18.5 ± 3.2 to -157.0 ± 5.2 mV and improved the stability of the niosomal formulations. Niosomes prepared with a Span 40:cholesterol molar ratio of 4:3 and 0.1% SDS showed good stability and the highest transdermal drug delivery among all tested formulations, with 2.75-fold higher transdermal flux of 20.26 ± 1.05 µg/(cm2·h) than that of aqueous salidroside solution. However, excess SDS increased the negative charge on the vesicle surface and hence repulsion with skin cells, leading to reduced drug entrapment efficiency and cellular uptake of niosomes. Although SDS in the niosomes dose-dependently increased the in vitro cytotoxicity of the formulation in skin cells, HaCaT and CCC-ESF-1 cell viability was ≥ 80% for formulations containing ≤0.1% SDS. No significant irritation was observed on rat skin with once-a-day topical application of the niosomal formulations for 7 consecutive days. Thus, SDS is a promising stabilizer for nanomedicines, including niosomes, for transdermal administration.

Ångstrom-scale silver particle-embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation.

Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing-related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel-induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)-gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.