Methoxy Polyethylene Glycol-poly Research Articles

Biodegradable cannabidiol: a potential nanotherapeutic for neuropathic pain

Abstract Cannabidiol (CBD) is a promising pharmaceutical agent to treat pain, inflammation, and seizures without the psychoactive effects of delta-9-tetrahydrocannabinol (THC). While CBD is highly lipophilic and can cross the blood-brain barrier (BBB), its bioavailability is limited and clearance is quick, limiting its effectiveness in the brain. To improve its effectiveness, we developed a unique nanoformulation consisting of CBD encapsulated within the biodegradable and biocompatible polymer, methoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA). mPEG-PLGA-CBD nanoparticles exhibited negligible cytotoxicity over a range of concentrations in CCK-8 assays performed in human astrocytes and brain microvascular endothelial cells. Furthermore, in an in-vitro BBB model, they exhibited rapid BBB permeability without harming BBB integrity. An in vivo Chronic Constriction Injury animal pain model was employed to study the efficacy of mPEG-PLGA-CBD in doses 1, 3 and 10 mg/kg, and it was found that 45–55 nm CBD nanoparticles with an encapsulation efficiency of 65 % can cross the BBB. Additionally, 3 and 10 mg/kg mPEG-PLGA-CBD nanoformulation provided prolonged analgesia in rats on day 2 and -4 post-injection, which we propose is attributed to the sustained and controlled release of CBD. Future studies are required to understand the pharmacokinetics of this nanoformulation.

Construction of Gene-Targeted Polymeric Microvesicles and Their In Vitro Targeted Binding Ability to Human Epidermal Growth Factor Receptor 2 (+) Breast Cancer Cells

The objective of this research was to construct the gene-targeted polymeric microvesicles (PMVs) and investigate their In Vitro ability to bind specifically to human epidermal growth factor receptor 2 (HER-2) (+) breast cancer (BC) cells. PMVs were formed using a block copolymer, methoxy polyethylene glycol-poly(L-lactide) (mPEG-PLLA), as the shell and encapsulating liquid perfluoropentane. Plasmid DNA and biotinylated HER-2 monoclonal antibody were conjugated to form the gene-loaded HER-2-targeted PMVs for BC cells. The characterization, physicochemical properties, and antibody coupling efficiency of the PMVs were evaluated. The PMVs were then co-cultured with HER-2 (+) BT474 cells, and their ability to target and bind to HER-2 (+) BC cells was observed under a microscope. Results revealed that the average particle size (APS) of the gene-targeted PMVs was (3.92±1.01) μm, with a uniform particle size distribution (PSD), smooth and transparent surfaces, and superior stability. The fluorescence intensity (FI) of PMVs in Group A was higher (16 vs. 9) to that in Group B, indicating a high binding rate (BR) (97.01%) between the PMVs and HER-2 monoclonal antibody. BT474 cells exhibited green fluorescence on their surface, which was stronger than that observed in SK-BR-3 cells, while no obvious green fluorescence was visualized in MDA-MB-231 cells or Hs578Bst cells. PMVs in Group A presented extensive binding to BT474 cells, mainly distributed on the cell membrane and surrounding areas. Only a few PMVs in Groups B and C were observed to bind to BT474 cells. In conclusion, the gene-loaded HER-2-targeted PMVs exhibited excellent stability and high specificity for binding to HER-2 (+) BC cells In Vitro, suggesting their potential application value.

Coacervate-mediated novel pancreatic cancer drug Aleuria Aurantia lectin delivery for augmented anticancer therapy

BackgroundPancreatic cancer, one of the cancers with the highest mortality rate, has very limited clinical treatment. Cancer cells express abnormal glycans on the surface, and some lectins with a high affinity for the glycans induce apoptosis in cancer. In this study, the efficacy of Aleuria Aurantia lectin (AAL) for the treatment of pancreatic cancer was evaluated and the efficacy improvement through AAL delivery with mPEGylated coacervate (mPEG-Coa) was investigated.MethodsAAL was treated with pancreatic cancer cells, PANC-1, and the expression level of caspase-3 and subsequent apoptosis was analyzed. In particular, the anticancer efficacy of AAL was compared with that of concanavalin A, one of the representative anticancer lectins. Then, methoxypolyethylene glycol-poly(ethylene arginylaspartate diglyceride), a polycation, was synthesized, and an mPEG-Coa complex was prepared with polyanion heparin. The AAL was incorporated into the mPEG-Coa and the release kinetics of the AAL from the mPEG-Coa and the cargo protection capacity of the mPEG-Coa were evaluated. Finally, improved anticancer ability through Coa-mediated AAL delivery was assessed.ResultsThese results indicated that AAL is a potential effective pancreatic cancer treatment. Moreover, mPEG-Coa rapidly released AAL at pH 6.5, an acidic condition in the cancer microenvironment. The initial rapid release of AAL effectively suppressed pancreatic cancer cells, and the continuous supply of AAL through the Coa transporter effectively inhibited proliferation recurrence of cancer cells.ConclusionAAL is a potential novel drug for the treatment of pancreatic cancer therapeutic agent. In addition, a continuous supply of drugs above the therapeutic threshold using mPEG-Coa could improve therapeutic efficacy.

Enhanced anticancer efficacy of primed natural killer cells via coacervate-mediated exogenous interleukin-15 delivery.

Effective exogenous delivery of interleukin (IL)-15 to natural killer (NK) cells with subsequent anticancer efficacy could be a promising immune cell-based cancer immunotherapy. For the protection of encapsulated cargo IL-15 while maintaining its bioactivity under physiological conditions, we utilized a coacervate (Coa) consisting of a cationic methoxy polyethylene glycol-poly(ethylene arginyl aspartate diglyceride) (mPEG-PEAD) polymer, anionic counterpart heparin, and cargo IL-15. mPEGylation into the backbone cation effectively preserved the colloidal stability of Coa in harsh environments and enhanced the protection of cargo IL-15 than normal Coa without mPEGylation. Proliferation and anticancer efficacy of primed NK cells through co-culture with multiple cancer cell lines were enhanced in the mPEG-Coa group due to the maintained bioactivity of cargo IL-15 during the ex vivo expansion of NK cells. These facilitated functions of NK cells were also supported by the increased expression of mRNAs related to anticancer effects of NK cells, including cytotoxic granules, death ligands, anti-apoptotic proteins, and activation receptors. In summary, our Coa-mediated exogenous IL-15 delivery could be an effective ex vivo priming technique for NK cells with sustained immune activation that can effectively facilitate its usage for cancer immunotherapy.

Size-dependent chemosensitization of doxorubicin-loaded polymeric nanoparticles for malignant glioma chemotherapy

ABSTRACT Chemotherapy is a traditional treatment method in clinical cancer treatment. However, it is limited due to the large toxic side effects of chemotherapeutics. Nanomedicines have shown great potential in the application of tumor therapy. The size of nanoparticles as a crucial factor in the enhanced permeability and retention (EPR) effect can be regulated for the enhanced chemotherapy. Therefore, we believe that regulation of nanoparticle size can be used as an effective sensitizer to enhance the therapeutic effect of chemotherapy drugs on tumors. Here, we prepared several nanoparticles of different hydrodynamic diameters commonly found in nanomedical applications by the diblock copolymer of methoxy polyethylene glycol-poly (‐caprolactone) (mPEG-PCL). The blood circulation effect and organ distribution in blood were detected by fluorescence labeled nanoparticles. We found that the small-sized nanoparticles exhibited much longer blood circulation time than the large-sized nanoparticles in vivo, and thus the nanoparticle concentration in the tumor tissue was relatively high. Systematic injection of the doxorubicin (DOX) loaded nanoparticles can effectively inhibit tumor growth. Compared to the free drug, tumor cells were much more sensitive to DOX loaded nanoparticles of small size. Our nano-drug delivery system has been proven to be safe and nontoxic in vivo and was suitable for use as a sensitizer in clinical oncology chemotherapy.

Oral administration co-delivery nanoparticles of docetaxel and bevacizumab for improving intestinal absorption and enhancing anticancer activity

In this study, to improve the intestinal absorption of small molecule chemotherapeutic drug docetaxel (DTX) and macromolecular monoclonal antibody drug bevacizumab (BVZ), we designed and prepared a type of co-delivery nanoparticles for the oral administration of DTX and BVZ. Carboxymethyl chitosan (CMC) and poly(lactic-co-glycolic acid) (PLGA) were used as the carrier of DTX nanoparticles (CPNPDTX), and methoxy polyethylene glycol-poly (β-amino ester) (mPEG-PAE) was used as the carrier of BVZ nanoparticles (PPNPBVZ). Then, the two nanoparticles were physically mixed in mass ratios to form mixed co-delivery nanoparticles, which was named as CPNPDTX&PPNPBVZ. The nanoparticles were characterized with pH-sensitive drug release property. CPNPDTX&PPNPBVZ could significantly increase the bioavailability of DTX and BVZ according to the more cellular uptake in Caco-2 cells and the higher absorption in the intestinal tissue. Compared with free DTX and BVZ, CPNPDTX&PPNPBVZ showed excellent cytotoxic effects on A549 cells. Our study revealed the potential of co-delivery nanoparticles of binary mixture of chemotherapeutic small molecule and macromolecular antibody drug as an oral administration therapeutic system.

Morphological transition of amphiphilic block copolymer/PEGylated phospholipid complexes induced by the dynamic subtle balance interactions in the self-assembled aggregates

Abstract Recently, there has been an increasing interest in the control of morphological transition of block copolymer aggregates. Here, we report how to control the morphological transition of methoxy polyethylene glycol–poly(d,l-lactic acid) (PDLLA–MPEG) by adding 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (DSPE–PEG). In the aggregates formed by dialyzing DSPE–PEG/PDLLA–MPEG mixed solutions against water, the two hydrophobic fatty acid tails of DSPE–PEG will preferentially anchor to the hydrophobic segment end of PDLLA–MPEG by interdigitating between these two tails and PDLLA segments. Consequently, DSPE–PEG and PDLLA–MPEG will form “ABA” temporary supra-amphiphiles in which A represents a poly(ethylene glycol) (PEG) chain segment and B is a mixed hydrophobic segment composed of PDLLA and DSPE segments; the repulsive force derived from the PEG segments of DSPE–PEG can affect the stability of “ABA” temporary supra-amphiphiles. Our results show that the dynamic subtle balance between the number of “ABA” temporary supra-amphiphiles formed and the strength of repulsive force between the PEG segments of DSPE–PEG drives the morphological structure of DSPE–PEG/PDLLA–MPEG aggregates to change from micelles to vesicles, then to semi-vesicles and finally to mixed micelles, with increasing DSPE–PEG additions.

Diameter of Carbon Nanotube-Directed Self-Assembly of Amphiphilic Block Copolymers.

The cooperative self-assembly of nanoparticles and amphiphilic block copolymers has attracted increasing interests as it offers effective routes to achieve nanocomposite supramolecular structures with desired structure and properties. The incorporation of nanoparticles usually tunes the self-assembly structure of block copolymers, as the copolymer–nanoparticle interactions may change the relative volume ratio of hydrophobic block/hydrophilic block copolymers. It should be noted that the micro-size length and the strong nonpolar feature of carbon nanotubes (CNTs) may cause the block copolymer–CNT interactions to differ from the the block copolymer–nanoparticle interactions. Herein, we show that the diameter of CNTs and the copolymer/CNT ratio have a profound effect on the self-assembly behavior of amphiphilic block copolymers. Upon the addition of carboxylated multi-walled carbon nanotubes (c-MWCNTs, diameter <8 nm,) to the methoxy polyethylene glycol-poly (D,L-lactic acid) (MPEG-PDLLA) solution, it is difficult to observe the c-MWCNTs directly in TEM images. However, it has been found that they form supramolecular nanocomposite structures with MPEG-PDLLA. Moreover, these supramolecular structures transform from core–shell spherical micelles into rod-like micelles and then into large composite aggregates with the increase of the c-MWCNT addition. However, in the case of the addition of c-MWCNTs with a diameter of 30–50 nm, the dispersed c-MWCNTs and spherical core–shell micelles could be observed simultaneously in the TEM images at a low c-MWCNT addition, and then the micelle structure disappeared and only well-dispersed c-MWNTs were observed in TEM images at a high c-MWCNT addition. A possible model was proposed to explain the rule of CNTs participating in the formation of copolymer/CNT nanocomposite structures. It was also shown that as-prepared copolymer/CNT supramolecular nanocomposites could be used as drug carriers, enabling the adjustment of the drug loading and release time.

Visual validation of the measurement of entrapment efficiency of drug nanocarriers

Entrapment efficiency (EE) is a crucial parameter for the evaluation of nanocarriers. The accurate measurement of EE demands clear separation of nanocarriers from free drugs, which so far has not been clearly validated due to a lack of functional tools to identify nanocarriers. Herein, an environment-responsive water-quenching fluorophore was employed to label and identify model nanocarriers, polycaprolactone nanoparticles (PN), methoxy polyethylene glycol-poly(d,l-lactic acid) polymeric micelles (PM) and solid lipid nanoparticles (SLN). The separation process of three commonly used methods (centrifugation, ultrafiltration and gel permeation chromatography) was visualized by live imaging. The separation efficiency of the centrifugation method is very poor, especially for PM (40 nm), SLN (100 nm) and PN (100 nm); only PN (200 nm) can be efficiently separated but at a consumption of enormous energy. The ultrafiltration method shows the best separation efficiency with only 0.32–0.93% of leakage of the nanocarriers. Gel permeation chromatography exhibits good separation as well but suffers from low recovery, a potential factor that might compromise the accuracy of EE measurement. In conclusion, the ultrafiltration method is the method of choice for efficient separation and accurate measurement of EE.

Transferrin-anchored poly(lactide) based micelles to improve anticancer activity of curcumin in hepatic and cervical cancer cell monolayers and 3D spheroids

In recent years, actively targeted drug delivery systems have been utilized in pre-clinical studies for site-specific delivery of drugs, which reduces toxicities associated with chemotherapy. This study reports the preparation of the tumor homing ligand, transferrin (Tf) anchored methoxy-polyethylene glycol-poly(d,l-Lactide) polymeric micelles (Tf-PP). Curcumin which possess wide anti-cancer activity was loaded into the micelles. Tf-PPC with average particle size of 132.16 ± 1.37 nm and encapsulation efficiency of 88.27 ± 2.53% showed a sustained drug release. The efficacy of Tf-PPC was studied in vitro in Tf-overexpressing human cervical carcinoma (HeLa) and human hepatoma (HepG2) cells. The mouse embryo fibroblast (NIH-3T3) cells were used as control cells. Tf-PPC showed higher internalization compared to non-targeted micelles (PPC). The curcumin-mediated cytotoxicity increased significantly following Tf-PPC treatment in both the tested cell lines. In NIH-3T3 cells, Tf conjugation did not differ in comparison to the non-targeted micelles. Further, the efficiency of Tf-PPC was studied in three-dimensional (3D) HeLa tumor spheroids. The Tf-PPC was efficiently internalized by the spheroidal structures, causing higher cytotoxicity and apoptosis compared to PPC. These results reveal that the newly developed, Tf-PPC could be employed as an effective chemotherapy in the treatment of Tf- overexpressing cancers.

Therapeutic Delivery of Simvastatin Loaded in PLA-PEG Polymersomes Resulted in Amplification of Anti-inflammatory Effects in Activated Microglia.

Simvastatin (Sim), a lipid-lowering drug has been studied in chronic neuroinflammation associated with degenerative brain disorders due to its potential protective properties against inflammatory reaction, oxidative damage, neuronal dysfunction, and death. Meanwhile, potential application of Sim in neuroinflammation will require a suitable delivery system that can overcome notable challenges pertaining to poor blood-brain barrier (BBB) permeability and side/off-target effects. Herein, we engineered and characterized nano-sized polymersomes loaded with Sim (Sim-Ps) using PEG-PdLLA (methoxy polyethylene glycol-poly(D,L) lactic acid) diblock co-polymers. Studies in BV2 microglia indicated that Sim-Ps was superior to Sim alone in suppressing nitric oxide (NO) and proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion against LPS activation. The effectiveness of Sim-Ps as compared with Sim alone, in attenuating NO and cytokine production by activated BV2 cells can be attributed to (a) colloidal stability of the delivery platform, (b) protracted release of biologically active Sim, and (c) particulate internalization coupled with enhanced Sim exposure to BV2 cells. Intranasal delivery in BALB/c mice demonstrated enhanced brain distribution with increasing time after administration. Overall data demonstrated suitability of PEG-PdLLA polymersomes in Sim delivery for potential application in treating neuroinflammation.

Preparation and Investigation of Amphiphilic Block Copolymers/Fullerene Nanocomposites as Nanocarriers for Hydrophobic Drug.

Biopolymer/inorganic material nanocomposites have attracted increasing interest as nanocarriers for delivering drugs owing to the combined advantages of both biopolymer and inorganic materials. Here, amphiphilic block copolymer/fullerene nanocomposites were prepared as nanocarriers for hydrophobic drug by incorporation of C60 in the core of methoxy polyethylene glycol-poly(d,l-lactic acid) (MPEG-PDLLA) micelles. The structure and morphology of MPEG-PDLLA/C60 nanocomposites were characterized using transmission electron microscopy, dynamic light scattering, high-resolution transmission electron microscopy, and thermal gravimetric analysis. It was found that the moderate amount of spherical C60 incorporated in the MPEG-PDLLA micelles may cause an increase in the molecular chain space of PDLLA segments in the vicinity of C60 and, thus, produce a larger cargo space to increase drug entrapment and accelerate the drug release from nanocomposites. Furthermore, sufficient additions of C60 perhaps resulted in an aggregation of C60 within the micelles that decreased the drug entrapment and produced a steric hindrance for DOX released from the nanocomposites. The results obtained provide fundamental insights into the understanding of the role of C60 in adjusting the drug loading and release of amphiphilic copolymer micelles and further demonstrate the future potential of the MPEG-PDLLA/C60 nanocomposites used as nanocarriers for controlled drug-delivery applications.

Preparation, Characterization, and Antitumor Evaluation of Electrospun Resveratrol Loaded Nanofibers

Resveratrol has been reported as a potential antitumor agent for several years. The possible application was greatly hampered by its poor solubility. The current study reported the construction of electrospun Resveratrol loaded nanofibers with methoxypolyethylene glycol-poly(caprolactone) (mPEG-PCL) block copolymers as drug carriers. Characterization studies showed the successful encapsulation of Rsv in the nanofibers with anin vitrosustained release pattern.In vitroXTT assay suggested the superior cytotoxicity of Rsv-NFs with more apoptosis induction on cancer cells. Cells that exposed to Rsv-NFs showed less clonogenic ability when compared to the equivalent dose of free Rsv. In addition, the migration and invasion ability of cells were also significantly lower when treated with Rsv-NFs. In thein vivostudy, local implantation of Rsv-NFs greatly increased the growth inhibitory effect compared to free Rsv. Therefore, results from the current study demonstrated a promising way to improve the antitumor effect of Rsv by nanofiber delivery.

In vitro anticancer efficacy by magnetic targeted nanocarrier with local delivery of paclitaxel

A magnetic nanoparticles-loaded polymeric nanocarrier was developed. Amphiphilic copolymer, methoxy polyethylene glycol-poly(D,L-lactide-co-glycolide)(MPEG-PLGA) could self-assemble to form nanomicelle with the help of emulsion-solvent evaporation technique. This nanocarrier with core-shell structure was loaded with magnetic iron oxide nanoparticles(IONPs) and anticancer drug paclitaxel(PTX). The hydrodynamic diameter of IONPs-PTX-loaded nanocarrier showed an average size of 110 nm with a polydispersity index(PDI) of 0.136, and its zeta potential was (–4.76±0.36) mV. The drug-loading content and encapsulation efficiency were 4.47% and 31.28%, respectively. In vitro drug release experiment was performed and a sustained release profile was observed. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay indicated that IONPs-PTX-loaded nanocarrier showed comparable cytotoxicity with free paclitaxel. When an external magnetic field was applied, the nanocarrier significantly localized at the target area, demonstrating that the nanocarrier could be used for potential magnetic targeted drug delivery.

Effect of Capsaicin-Loading Nanoparticles on Gliomas.

Capsaicin is recognized as a natural tumor preventive compound and exhibits a remarkable anticancer action. Strong inhibitory role of capsaicin on gliomas has been well documented. However, the use of capsaicin is limited due to its hydrophobicity, low affinity, and short half-life. The present study aimed to explore the physiochemical characteristics of the capsaicin-loading nanoparticles prepared by methoxy polyethylene glycol-poly(caprolactone) (mPEG-PCL) amphiphilic block copolymer. It also aimed to evaluate the ability of the nanoparticles to cross the blood-brain barrier. Additionally, the uptake of nanoparticles in the glioma cells and its ability to inhibit cell proliferation were tested in human glioblastoma U251 cells. mPEG-PCL amphiphilic block copolymer was synthesized using the ring-opening polymerization method, and the capsaicin-loading nanoparticles were prepared with the solvent diffusion method. In vitro drug release assay revealed that the capsaicin-loading nanoparticles presented a slow-release characteristic. Coculture of the human glioblastoma U251 cells and the fluorescein-loading nanoparticles showed the uptake of nanoparticles in U251 cells by endocytosis. We found that the NIR-797 isothiocyanate-loading nanoparticles can cross the blood-brain barrier. In addition, the capsaicin-loading nanoparticle showed a remarkable inhibition on the growth of U251 cells. The efficacy of the capsaicin-loading nanoparticles against tumor cells was significantly superior to the capsaicin at low concentrations. It is concluded that the capsaicin-loading nanoparticles can provide an extremely promising approach for chemotherapy of gliomas.

Doxorubicin-loaded polypeptide nanorods based on electrostatic interactions for cancer therapy

An amphiphilic anionic polypeptide, methoxypolyethylene glycol–poly (glutamic acid) (mPEG–PGA), was synthesized, characterized and evaluated as a nanocarrier for the cationic anticancer drug doxorubicin hydrochloride (DOX·HCl). The complex self-assembled into nanorods in aqueous solutions via electrostatic interactions and exhibited a superior drug loading content (50.8%) and drug loading efficiency (90.2%). The average major axis of the drug-loaded nanorods was approximately 300nm, as determined by transmission electron microscopy. An in vitro release assay showed that drug-loaded nanorods exhibited pH-sensitivity and sustained release. Haemolysis assays demonstrated that the polypeptide was haemocompatible, and the polypeptide drug carrier significantly reduced the haemolysis ratio of DOX·HCl. The pharmacokinetics study showed that DOX-loaded nanorods significantly prolonged the resident time in blood. An in vitro cytotoxicity study and cellular uptake assays demonstrated that the DOX-loaded nanorods resulted in higher cell proliferation inhibition and a higher level of tumour cell uptake in A549 cells than with free DOX·HCl. The prolonged circulation and enhanced antitumor efficacy of DOX-loaded nanorods shows promise for efficient cancer chemotherapy.

Sorption of triclosan on electrospun fibrous membranes: Effects of pH and dissolved organic matter

Abstract Three hydrophobic and polyporous electrospun fibrous membranes (EFMs) were prepared by electrospinning methoxy polyethylene glycol-poly(lactide-co-glycolide) (MPEG-PLGA), poly( d , l -lactide-co-glycolide) (PLGA) and poly( d , l -lactide) (PDLLA). The effects of pH and dissolved organic matter (DOM) on triclosan (TCS) sorption by EFMs in aqueous solution were investigated. The results indicated that hydrogen bonding, hydrophobic and π–π bonding interactions led to fast adsorption, which governed the adsorption rates of TCS onto EFMs. The maximum sorption capacities of MPEG-PLGA, PLGA and PDLLA reached 130, 93 and 99 mg g −1 , respectively, which were in positive correlation with their pore volumes and influenced by pore filling processes. The solution pH could significantly influence the TCS sorption by EFMs. In acid condition, protonated TCS facilitated their sorption onto EFMs. No obvious sorption was observed in alkaline condition due to repulsive forces between negatively charged EFMs and deprotonated TCS ( pK a = 7.9). The presence of DOM inhibited TCS sorption onto EFMs due to competitive adsorption. The results could be due to the occupation of the adsorption sites and the blockage of the pore entrance by DOM.

Evaluation of self-assembled HCPT-loaded PEG-b-PLA nanoparticles by comparing with HCPT-loaded PLA nanoparticles.

We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(d,l-lactide) (PEG-b-PLA) and PLA, respectively. Both HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of −31.2 and −45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG-b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG-b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG-b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

A comparative in vitro evaluation of self-assembled PTX-PLA and PTX-MPEG-PLA nanoparticles

We present a dialysis technique to direct the self-assembly of paclitaxel (PTX)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(d,l-lactide) (MPEG-PLA) and PLA, respectively. The composition, morphology, particle size and zeta potential, drug loading content, and drug encapsulation efficiency of both PTX-PLA NPs and PTX-MPEG-PLA NPs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, dynamic light scattering, electrophoretic light scattering, and high-performance liquid chromatography. The passive targeting effect and in vitro cell viability of the PTX-MPEG-PLA NPs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PTX-PLA NPs. The results showed that the PTX-MPEG-PLA NPs and PTX-PLA NPs presented a hydrodynamic particle size of 179.5 and 441.9 nm, with a polydispersity index of 0.172 and 0.189, a zeta potential of −24.3 and −42.0 mV, drug encapsulation efficiency of 18.3% and 20.0%, and drug-loaded content of 1.83% and 2.00%, respectively. The PTX-MPEG-PLA NPs presented faster release rate with minor initial burst compared to the PTX-PLA NPs. The PTX-MPEG-PLA NPs presented superior cell cytotoxicity and excellent cellular uptake compared to the PTX-PLA NPs. These results suggested that the PTX-MPEG-PLA NPs presented more desirable characteristics for sustained drug delivery compared to PTX-PLA NPs.

Fabrication of a magnetite nanoparticle-loaded polymeric nanoplatform for magnetically guided drug delivery

We developed a magnetite nanoparticle-loaded polymeric nanoplatform for magnetically guided 10-hydroxycamptothecin(HCPT) delivery. The nanoplatform was fabricated by simultaneously incorporating magnetite nanoparticles(NPs) and HCPT into the polymer micelle self-assembled from methoxy polyethylene glycol-poly(D,L-lactide-co-glycolide)(MPEG-PLGA) copolymer. Successful loading of HCPT into the nanoplatform was confirmed by Fourier transform infrared(FTIR) spectroscopy. Subsequently, we examined the in vitro antitumor efficacy of free HCPT and nanoplatform against three different cancer cell lines—HeLa, A549 and HepG2. Flow cytometric analysis was conducted to reveal the cell apoptosis caused by free HCPT and nanoplatform. Finally, the magnetic targeting property of the nanoplatform was evaluated by a self-designed in vitro experiment.