Enhance Drug Penetration Research Articles

Laser-induced vapor nanobubbles improve diffusion in biofilms of antimicrobial agents for wound care

Being responsible for delayed wound healing, the presence of biofilms in infected wounds leads to chronic, and difficult to treat infections. One of the reasons why antimicrobial treatment often fails to cure biofilm infections is the reduced penetration rate of antibiotics through dense biofilms. Strategies that have the ability to somehow interfere with the integrity of biofilms and allowing a better penetration of drugs are highly sought after. A promising new approach is the use of laser-induced vapor nanobubbles (VNB), of which it was recently demonstrated that it can substantially enhance the penetration of antibiotics into biofilms, resulting in a marked improvement of the killing efficiency. In this study, we examined if treatment of biofilms with laser-induced vapor nanobubbles (VNB) can enhance the potency of antimicrobials which are commonly used to treat wound infections, including povidone-iodine, chlorhexidine, benzalkonium chloride, cetrimonium bromide and mupirocin. Our investigations were performed on Pseudomonas aeruginosa and Staphylococcus aureus biofilms, which are often implicated in chronic wound infections. Pre-treatment of biofilms with laser-induced VNB did enhance the killing efficiency of those antimicrobials which experience a diffusion barrier in the biofilms, while this was not the case for those compounds for which there is no diffusion barrier. The magnitude of the enhanced potency was in most cases similar to the enhancement that was obtained when the biofilms were completely disrupted by vortexing and sonication. These results show that laser-induced VNB are indeed a very efficient way to enhance drug penetration deep into biofilms, and pave the way towards clinical translation of this novel approach for treatment of wound infections.

Photodynamic therapy for skin cancer: How to enhance drug penetration?

Photodynamic therapy (PDT) induced by protoporphyrin IX (PpIX) has been widely used in dermatological practices such as treatment of skin cancers. Clearance rate depends on different factors such as light irradiation, skin oxygenation and drug penetration. The poor penetration of 5-aminolevulinic acid (5-ALA) with topical application is limited and restrains the production of PpIX which could restrict PDT outcomes. This review will focus on techniques already used to enhance drug penetration in human skin, and will present their results, advantages, and drawbacks. Chemical and physical pretreatments will be discussed. Chemical pre-treatments comprise of drug formulation modification, use of agents that modify the heme cycle, enhance PpIX formation, and the combination of differentiation-promoting agent prior to PDT. On the other hand, physical pretreatments affect the skin barrier by creating holes in the skin or by removing stratum corneum. To promote drug penetration, iontophoresis and temperature modulation are interesting alternative methods. Cellular mechanisms enrolled during chemical or physical pretreatments have been investigated in order to understand how 5-ALA penetrates the skin, why it is preferentially metabolized in PpIX in tumour cells, and how it could be accumulated in deeper skin layers. The objective of this review is to compare clinical trials that use innovative technology to conventional PDT treatment. Most of these pretreatments present good or even better clinical outcomes than usual PDT.

Advancement of Lipid-Based Nanocarriers and Combination Application with Physical Penetration Technique.

On account of the advantages of transdermal delivery and the application situation of transcutaneous technology in transdermal delivery, the article critically comments on nanosystems as permeation enhancement model. Nanosystems possess great potential for transcutaneous drug delivery. This review focuses on recent advances in lipid-based nanocarriers, including liposome, transfersomes, ethosomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers and combination application of the lipid-based nanocarriers with microneedle, iontophoresis, electroporation and sonophoresis in the field for the development of the transdermal drug delivery system. We attempted to give an overview of lipid-based nanocarriers with the aim to improve transdermal and dermal drug delivery. A special focus is given to the nanocarrier composition, characteristic and interaction mechanisms through the skin. Recent combination applications of lipid-based nanocarriers with the physical penetration technology demonstrate the superiority of the combined use of nanocarriers and physical methods in drug penetration enhancement compared to their single use. In the future, lipidbased nanocarriers will play a greater role in the field of transdermal and dermal drug delivery.

Drug penetration enhancement techniques in ablative fractional laser assisted cutaneous delivery of indocyanine green.

Background and ObjectivesTopical drug delivery can be increased by pretreatment of the skin with ablative fractional laser (AFXL). Several physical penetration enhancement techniques have been investigated to further improve AFXL‐assisted drug delivery. This study investigated the influence of three of these techniques, namely massage, acoustic pressure wave treatment, and pressure vacuum alterations (PVP) on the distribution of the fluorescent drug indocyanine green (ICG) at different depths in the skin after topical application on AFXL pretreated skin.Materials and MethodsIn ex vivo human skin, test regions were pretreated with AFXL (10,600 nm, channel depth 300 μm, channel width 120 μm, density 15%). Subsequently, ICG was applied, followed by massage, acoustic pressure wave treatment or PVP. ICG fluorescence intensity (FI) was assessed after 1, 3, and 24 hours at several depths using fluorescence photography.ResultsFI was higher when using enhancement techniques compared to control (AFXL‐only) up to 3 hours application time (P < 0.05). After 3 hours, mean surface FI was highest after acoustic pressure wave treatment (61.5 arbitrary units; AU), followed by massage (57.5AU) and PVP (46.9AU), respectively (for comparison: AFXL‐only 31.6AU, no pretreatment 14.9AU). Comparable or higher FI was achieved already after 1 hour with enhancement techniques compared to 3–24 hours application time without. After 24 hours, no significant differences between enhancement techniques and AFXL‐only were observed (P = 0.31).ConclusionPenetration enhancement techniques, especially acoustic pressure wave treatment and massage, result in improved drug accumulation in AFXL‐pretreated skin and reduce the application time needed. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Core-multishell nanocarriers enhance drug penetration and reach keratinocytes and antigen-presenting cells in intact human skin

In reconstructed skin and diffusion cell studies, core-multishell nanocarriers (CMS-NC) showed great potential for drug delivery across the skin barrier. Herein, we investigated penetration, release of dexamethasone (DXM), in excised full-thickness human skin with special focus on hair follicles (HF).Four hours and 16 h after topical application of clinically relevant dosages of 10 μg DXM/cm2 skin encapsulated in CMS-NC (12 nm diameter, 5.8% loading), presence of DXM in the tissue as assessed by fluorescence microscopy of anti-DXM-stained tissue sections as well as ELISA and HPLC-MS/MS in tissue extracts was enhanced compared to standard LAW-creme but lower compared to DXM aqueous/alcoholic solution. Such enhanced penetration compared to conventional cremes offers high potential for topical therapies, as recurrent applications of corticosteroid solutions face limitations with regard to tolerability and fast drainage. The findings encourage more detailed investigations on where and how the nanocarrier and drug dissociate within the skin and what other factors, e.g. thermodynamic activity, influence the penetration of this formulations.Microscopic studies on the spatial distribution within the skin revealed accumulation in HF and furrows accompanied by limited cellular uptake assessed by flow cytometry (up to 9% of total epidermal cells). FLIM clearly visualized the presence of CMS-NC in the viable epidermis and dermis. When exposed in situ a fraction of up to 25% CD1a+ cells were found within the epidermal CMS-NC+ population compared to approximately 3% CD1a+/CMS-NC+ cells after in vitro exposure in short-term cultures of epidermal cell suspensions. The latter reflects the natural percentage of Langerhans cells (LC) in epidermis suspensions and indicated that CMS-NC were not preferentially internalized by one cell type. The increased CMS-NC+ LC proportion after exposure within the tissue is in accordance with the strategic suprabasal LC-localization. More specifically we postulate that the extensive dendrite meshwork, their position around HF orifices and their capacity to modulate tight junctions facilitated a preferential uptake of CMS-NC by LC within the skin. This newly identified aspect of CMS-NC penetration underlines the potential of CMS-NC for dermatotherapy and encourages further investigations of CMS-NC for the delivery of other molecule classes for which intracellular delivery is even more crucial.

Acoustic disruption of tumor endothelium and on-demand drug delivery for cancer chemotherapy

Chemotherapy has been the most widely used treatment against cancer, however, it is limited by its systemic toxicity as well as resistance developed by tumors’ physical barriers. Herein, we propose a novel acoustically-mediated treatment regime to on-demand release therapeutics and disrupt tumor structures. By programming a high intensity focused ultrasound transducer, we can locally and digitally release gemcitabine (GEM) as well as open the local blood–tumor barrier or even tumor stroma to enhance intratumor drug delivery via acoustically-oscillating bubbles and liposomes. In our experiments, we modeled tumor endothelium by culturing a monolayer of murine endothelial cells (2H11) on transwell membrane. We locally disrupted the cultured endothelium to enhance drug penetration by using perfluorocarbon liquid droplets as breaking probes and protoporphyrin IX hybridized liposomes as drug carriers. We also demonstrated an on-demand release of GEM by digitally triggering the break of drug carriers. Moreover, we validated the acoustic tumor endothelium disruption in vivo by monitoring penetration of dye (Evans blue) in solid tumors. Therefore, we present an acoustically-mediated delivery method that both releases drug on-demand locally and opens the blood–tumor barrier to enhance drug penetration. This sets the ground for further clinical cancer therapy to improve many systemic cancer treatments.

Mitoxantrone-preloaded water-responsive phospholipid-amorphous calcium carbonate hybrid nanoparticles for targeted and effective cancer therapy.

BackgroundThe application of mitoxantrone (MIT) in cancer therapy has been severely limited by its inherent drawbacks. In addition, effective cancer therapy calls for drug release systems capable of enforcing drug release within cancer cells in response to infinite stimulant with enhanced drug penetration capability.MethodsMIT-preloaded phospholipid-amorphous calcium carbonate hybrid nanoparticles (PL/ACC-MIT) that surface modified with PL shell (containing shielding polymer polyethylene glycol and targeting moiety folic acid) were prepared by a facile solvent-diffusion method.ResultsIt has been proven that the resulting PL/ACC-MIT nanoparticles demonstrated satisfactory stability against various aqueous environments with minimal drug leakage and exerted strong targeting capability but selective preference to the folate receptor-overexpressing cell line. In contrast, once exposed to the enzyme-abundant and acidic environments of cancer cells, the PL/ACC-MIT nanoparticles can readily decompose to facilitate quick drug release and enhanced drug penetration to yield preferable antitumor effect both in vitro and in vivo.ConclusionIn this study, MIT-preloaded water-responsive hybrid nanoparticles with increased stability, targetability, controlled drug release, and enhanced drug penetration were successfully developed, which might be a candidate for targeted and effective cancer therapy.

Enhanced Transdermal Drug Delivery by Sonophoresis and Simultaneous Application of Sonophoresis and Iontophoresis

Transdermal drug delivery has advantages of topical drug administration compared to the other conventional administration methods. However, the skin penetration of drugs is limited by the barrier properties of stratum corneum. The combinational strategy has been investigated to improve the skin permeability of the drug. For this study, we devised an improved device that can perform not only the single application of sonophoresis or iontophoresis but also the simultaneous application. The enhancement effect of sonophoresis was evaluated for various cosmeceutical drugs using a Franz diffusion cell. The enhancement ratio of niacinamide and retinol with sonophoresis was increased to 402% and 292%, respectively. The relationship was found between the enhancement effect of sonophoresis and the physicochemical properties of drugs. In particular, the simultaneous treatment of sonophoresis and iontophoresis enhanced skin penetration of glutamic acid to 240% using the fabricated device. The simultaneous application showed significantly higher enhancement ratio than application of sonophoresis or iontophoresis alone. Moreover, the improved device achieved skin penetration enhancement of various cosmeceutical drugs with lower intensity and a short application time. This combined strategy of transdermal physical enhancement methods is advantageous in terms of decline in energy density, thereby reducing the skin irritation. The miniaturized device with sonophoresis and iontophoresis is a promising approach due to enhanced transdermal drug delivery and feasibility of self-administration in cosmetic and therapeutic fields.

Drug-Homogeneity Index in Mass-Spectrometry Imaging.

Enhancing drug penetration in solid tumors is an interesting clinical issue of considerable importance. In preclinical research, mass-spectrometry imaging is a promising technique for visualizing drug distribution in tumors under different treatment conditions and its application in this field is rapidly increasing. However, in view of the huge variability among MSI data sets, drug homogeneity is usually manually assessed by an expert, and this approach is biased by interobserver variability and lacks reproducibility. We propose a new texture-based feature, the drug-homogeneity index (DHI), which provides an objective, automated measure of drug homogeneity in MSI data. A simulation study on synthetic data sets showed that previously known texture features do not give an accurate picture of intratumor drug-distribution patterns and are easily influenced by the tumor-tissue morphology. The DHI has been used to study the distribution profile of the anticancer drug paclitaxel in various xenograft models, which were either pretreated or not pretreated with antiangiogenesis compounds. The conclusion is that drug homogeneity is better in the pretreated condition, which is in agreement with previous experimental findings published by our group. This study shows that DHI could be useful in preclinical studies as a new parameter for the evaluation of protocols for better drug penetration.

Acoustic Streaming in a Soft Tissue Microenvironment

We demonstrated that sound can push fluid through a tissue-mimicking material. Although acoustic streaming in tissue has been proposed as a mechanism for biomedical ultrasound applications, such as neuromodulation and enhanced drug penetration, streaming in tissue or acoustic phantoms has not been directly observed. We developed a material that mimics the porous structure of tissue and used a dye and a video camera to track fluid movement. When applied above an acoustic intensity threshold, a continuous focused ultrasound beam (spatial peak time average intensity: 238 W/cm2, centre frequency: 5 MHz) was found to push the dye axially, that is, in the direction of wave propagation and in the radial direction. Dye clearance increased with ultrasound intensity and was modelled using an adapted version of Eckart's acoustic streaming velocity equation. No microstructural changes were observed in the sonicated region when assessed using scanning electron microscopy. Our study indicates that acoustic streaming can occur in soft porous materials and provides a mechanistic basis for future use of streaming for therapeutic or diagnostic purposes.

Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles.

Targeted delivery of anticancer drugs with nanocarriers can reduce side effects and ameliorate therapeutic efficacy. However, poorly perfused and dysfunctional tumor vessels limit the transport of the payload into solid tumors. The use of tumor-penetrating nanocarriers might enhance tumor uptake and antitumor effects. A peptide containing a tissue-penetrating (TP) consensus motif, capable of recognizing neuropilin-1, is here fused to a neuroblastoma-targeting peptide (pep) previously developed. Neuroblastoma cell lines and cells derived from both xenografts and high-risk neuroblastoma patients show overexpression of neuropilin-1. In vitro studies reveal that TP-pep binds cell lines and cells derived from neuroblastoma patients more efficiently than pep. TP-pep, after coupling to doxorubicin-containing stealth liposomes (TP-pep-SL[doxorubicin]), enhances their uptake by cells and cytotoxic effects in vitro, while increasing tumor-binding capability and homing in vivo. TP-pep-SL[doxorubicin] treatment enhances the Evans Blue dye accumulation in tumors but not in nontumor tissues, pointing to selective increase of vascular permeability in tumor tissues. Compared to pep-SL[doxorubicin], TP-pep-SL[doxorubicin] shows an increased antineuroblastoma activity in three neuroblastoma animal models mimicking the growth of neuroblastoma in humans. The enhancement of drug penetration in tumors by TP-pep-targeted nanoparticles may represent an innovative strategy for neuroblastoma.

Intranasal niosomes of nefopam with improved bioavailability: preparation, optimization, and in-vivo evaluation.

ObjectiveOne of the greatest challenges drug formulation is facing is poor bioavailability via oral route. In this regard, nasal drug delivery has been commonly used as an alternative route to improve drug bioavailability. Nefopam hydrochloride (NF) is an analgesic drug that suffers from poor bioavailability due to extensive metabolism in liver. Accordingly, the goal of the present study was to improve NF bioavailability via niosomal-based formulation designed for intranasal delivery.Materials and methodsVesicles were developed by mixing surfactants (Span 20, Span 40, Span 80, and Span 85) at four molar ratios of 1:1, 1:2, 1:3, and 1:4 of cholesterol to surfactant. Entrapment efficiency, particle size, zeta potential, release percentage, ex-vivo permeation parameters, and niosomes’ stability were determined. Also, the pharmacokinetic parameters of the optimized formula in in-situ gel base were measured in rats.ResultsNiosomes showed entrapment efficiency .80%, particle size ,550 nm, and zeta potential ranging from -16.8±0.13 to -29.7±0.15. The produced vesicles showed significantly higher amounts of drug permeated across nasal mucosa (2.5 folds) and prolonged NF release compared with NF solution. Stability studies of optimum formula showed nonsignificant changes in niosomes parameters over a storage period of 6 months. The in-vivo studies showed a 4.77-fold increase in bioavailability of optimized nasal niosomes compared with oral solution of drug.ConclusionThe obtained results revealed the great ability of the produced NF-loaded nio-somes to enhance drug penetration through nasal mucosa and improve its relative bioavailability compared with NF oral solution.

Liposomes can both enhance or reduce drugs penetration through the skin

The adequate formulation of topical vehicles to treat skin diseases is particularly complex. A desirable formulation should enhance the accumulation of the active drugs in the target tissue (the skin), while avoiding the penetration enhancement to be so large that the drugs reach the systemic circulation in toxic amounts. We have evaluated the transcutaneous penetration of three drugs chosen for their widely variable physicochemical properties: Amphotericin B, Imiquimod and Indole. We incorporated the drugs in fluid or ultra-flexible liposomes. Ultra-flexible liposomes produced enhancement of drug penetration into/through human skin in all cases in comparison with fluid liposomes without detergent, regardless of drug molecular weight. At the same time, our results indicate that liposomes can impede the transcutaneous penetration of molecules, in particular small ones.

Iontophoretic Drug Delivery in the Oral Cavity.

Iontophoresis is a noninvasive method to enhance systemic and local drug delivery by the application of an electric field. For systemic drug delivery in the oral cavity, iontophoresis was studied primarily for transbuccal delivery. Significant enhancement of drug delivery was observed in buccal iontophoresis compared to passive transport for different drugs. For local drug delivery in the oral cavity, iontophoresis could enhance drug penetration into the enamel, dentin, and other oral tissues for the treatment of oral diseases. Iontophoresis was evaluated in dentistry such as to produce local anesthesia and treat tooth decalcification and hypersensitivity, but this technology has not been fully utilized. The most common drugs in these evaluations were fluoride and lidocaine. In general, there is limited knowledge of the mechanisms of iontophoresis in the oral tissues. In vivo animal and human studies have suggested that iontophoresis is safe in the oral cavity under the conditions investigated. The present review covers the topics of iontophoretic drug delivery in the oral cavity for both systemic and local treatments. The anatomy and diseases in the oral cavity for iontophoretic drug delivery are also briefly reviewed, and the challenges for this drug delivery method are discussed.

Tinea Capitis: Current Review of the Literature

This review summarizes the fungal literature currently available for tinea capitis (TC), as well as providing data for clinical utility. Available studies in TC are scarce; however, they provide important information about efficacy and outcome in clinical practice. Treatment of TC is effective; however, it requires a minimum of 1 month. Systemic treatment is often required to favor enhance drug penetration into the deep part of the hair follicle. The newest oral antifungal has higher efficacy rates than conventional therapy, as well as much shorter duration of treatment but at higher costs. We perform a review of the literature including treatment schemes.

Facile synthesis of pH-responsive polymersomes based on lipidized PEG for intracellular co-delivery of curcumin and methotrexate.

pH-responsive polymersomes were obtained by self-assembling of a carboxyl-terminated PEG amphiphile achieved via esterification of PEG diacid with PEG40stearate. The obtained vesicular systems had spherical shape and a mean diameter of 70 nm. The pH sensitivity was assessed by measuring the variations of particles mean diameter after incubation in media mimicking the physiological (pH 7.4) or tumor (pH 5.0) conditions, recording a significant increase of the vesicles dimensions at acidic pH. The ability of the polymersomes to carry both hydrophobic and hydrophilic drugs was evaluated by loading the vesicles with curcumin and methotrexate, respectively, obtaining high encapsulation efficiencies and pH-dependent release profiles. The drug-loaded polymeric vesicles exhibited improved cytotoxic potential against MCF-7 cancer cell line and were found to be highly hemocompatible. Finally, cellular uptake experiments on MCF-7 cancer cells were conducted to demonstrate the ability of the designed polymersomes to enhance drug penetration inside the cells.

Bromelain-immobilized and lactobionic acid-modified chitosan nanoparticles for enhanced drug penetration in tumor tissues

Tumor extracellular matrix (ECM) still remains a major barrier that hinders the diffusion of drug in tumor parenchyma. We design a lactobionic acid (LA) and bromelain dual-functional nanoparticles as doxorubicin carriers. LA can increase the nanoparticles' tumor-targeting ability, while bromelain can enhance the permeation of nanoparticles in tumor parenchyma due to the hydrolytic activity to ECM. The chemical structures of these modified macromolecules were characterized by 1H NMR, FT-IR and UV spectrum. Drug-loaded nanoparticles as final drug formulations were observed in terms of size, zeta potential and micromorphology. Monolayer cells and three-dimensional cell spheroids were used to investigate the influence of LA and bromelain on the nanoparticles' cellular uptake, cytotoxicity, accumulation and penetration. In vivo drug distribution and antitumor activity results demonstrated that bromelain increased nanoparticles penetration and diffusion ability in tumor area upon the digestion of ECM, leading to higher drug concentration in tumor area and superior antitumor effect.

Lipase-Triggered Water-Responsive "Pandora's Box" for Cancer Therapy: Toward Induced Neighboring Effect and Enhanced Drug Penetration.

Insufficient drug release as well as poor drug penetration are major obstacles for effective nanoparticles (NPs)-based cancer therapy. Herein, the high aqueous instability of amorphous calcium carbonate (ACC) is employed to construct doxorubicin (DOX) preloaded and monostearin (MS) coated "Pandora's box" (MS/ACC-DOX) NPs for lipase-triggered water-responsive drug release in lipase-overexpressed tumor tissue to induce a neighboring effect and enhance drug penetration. MS as a solid lipid can prevent potential drug leakage of ACC-DOX NPs during the circulatory process, while it can be readily be disintegrated in lipase-overexpressed SKOV3 cells to expose the ACC-DOX core. The high aqueous instability of ACC will lead to burst release of the encapsulated DOX to induce apoptosis and cytotoxicity to kill the tumor cells. The liberated NPs from the dead or dying cells continue to respond to the ubiquitous aqueous environment to sufficiently release DOX once unpacked, like the "Pandora's box", leading to severe cytotoxicity to neighboring cells (neighboring effect). Moreover, the continuously released free DOX molecules can readily diffused through the tumor extracellular matrix to enhance drug penetration to deep tumor tissue. Both effects contribute to achieve elevated antitumor benefits.

Combined use of nanocarriers and physical methods for percutaneous penetration enhancement.

Dermal and transdermal drug delivery (due to its non-invasiveness, avoidance of the first-pass metabolism, controlling the rate of drug input over a prolonged time, etc.) have gained significant acceptance. Several methods are employed to overcome the permeability barrier of the skin, improving drug penetration into/through skin. Among chemical penetration enhancement methods, nanocarriers have been extensively studied. When applied alone, nanocarriers mostly deliver drugs to skin and can be used to treat skin diseases. To achieve effective transdermal drug delivery, nanocarriers should be applied with physical methods, as they act synergistically in enhancing drug penetration. This review describes combined use of frequently used nanocarriers (liposomes, novel elastic vesicles, lipid-based and polymer-based nanoparticles and dendrimers) with the most efficient physical methods (microneedles, iontophoresis, ultrasound and electroporation) and demonstrates superiority of the combined use of nanocarriers and physical methods in drug penetration enhancement compared to their single use.

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel.

PurposePolymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)-block-poly (d,l-lactide) (mPEG-PDLLA).MethodsPTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated.ResultsThe size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was −19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC0−t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications.ConclusionThese results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.