Delivery System For Hydrophobic Drugs Research Articles

Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid

BackgroundThermosensitive micelles with rigid cores that exhibit a reversible lower critical solution temperature at 30–35 °C can be applied for drug delivery.MethodHydrophilic monomethoxy poly(ethylene glycol) was conjugated to hydrophobic deoxycholic acid to prepare monomethoxy poly(ethylene glycol)-deoxycholic acid (mPEG-DC). Micelle formation and thermosensitive solution behavior were studied using various methods, including hydrophobic dye solubilization, transmission electron microscopy, dynamic light scattering, turbidity measurement, microcalorimetry, and 1H-NMR spectroscopy. Drug release from the thermosensitive micelles was demonstrated using estradiol, a model drug.ResultsThe mPEG-DC formed micelles with a critical micelle concentration of 0.05 wt.% and an average size of 15 nm. Aqueous mPEG-DC solutions exhibit a lower critical solution temperature (LCST) that is independent of concentration and reversible over heating and cooling cycles. The LCST transition is an entropically driven process involving dehydration of the PEG shell. The thermosensitive mPEG-DC micelles with rigid DC cores were applied as an estradiol delivery system in which estradiol was released, without initial burst, over the 16 days in a diffusion-controlled manner.ConclusionsThis study suggests that mPEG-DCs form thermosensitive micelles with rigid cores that can function as an excellent diffusion-controlled hydrophobic drug delivery system without initial burst release.Graphical Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid

Layer-by-layer self-assembly of giant polyelectrolyte microcapsules templated by microbubbles as potential hydrophilic or hydrophobic drug delivery system

Giant polyelectrolyte microcapsules (GMs) with huge cavities and extremely low wall-to-diameter ratios have superior high loading ability and controlled permeability. However, the series of problems brought by template removal seriously impede their applications in biomedicine. In this work, a combination of microbubbles (MBs) as templates and layer-by-layer (LbL) self-assembly technology was used to fabricate GMs as potential hydrophilic or hydrophobic drug delivery system by depositing poly (allylamine hydrochloride) and poly(styrene sulfonate) onto monodispersity bovine serum albumin or liposome (Lipo) MBs. CLSM and AFM images showed that the GMs have a diameter of 100.4 ± 14.2 μm and a thickness of nearly 100 nm. Due to the difficulty in loading hydrophobic molecules into the hydrophilic structure of LbL capsules, we focused on encapsulating paclitaxel (PTX) into GMs based on PTX-loaded Lipo MBs, which presented high-drug loading and notable sustained-release effects. Collectively, these GMs have tremendous potential for drug delivery.

Dialysis-derived urchin-like supramolecular assembly of tannic acid and paclitaxel with high porosity.

Co-crystallization of active pharmaceutical ingredients (APIs) with pharmaceutically acceptable additives has emerged as an alternative to current drug delivery systems for hydrophobic drugs, due to their high drug loading efficiency. During this process, we herein report that tannic acid (TA) can be used as an amphiphilic stabilizer for the model drug, paclitaxel (PTX), that results in the shape and morphology variations of the synthesized microstructures, depending on the synthetic environment. We observed that rapid co-precipitation of PTX and TA via dialysis in water resulted in unprecedented urchin-like supramolecular microstructures with high porosity. On the other hand, slow co-precipitation for several hours under static conditions without dialysis exhibited bundles of straight TA-coated PTX fibers without any pores. This was plausibly due to the dynamic change of both the building block concentration and the solvent composition occurring during the transition of the kinetic product to the thermodynamic product. Interestingly, the synthesized urchin-like porous structure further rapidly transformed into a spherical shape through the interaction with serum proteins by remodeling of the non-covalent interactions, which contributed to the overall therapeutic efficacy tested in vitro. Our results provide knowledge on the self-assembly behavior of the hydrophobic drug and amphiphilic stabilizer under dynamic conditions, and contribute to the development of novel strategies in designing drug formulations.

Mixed Pluronic-Cremophor Polymeric Micelles as Nanocarriers for Poorly Soluble Antibiotics-The Influence on the Antibacterial Activity.

In this work, novel polymeric mixed micelles from Pluronic F127 and Cremophor EL were investigated as drug delivery systems for Norfloxacin as model antibiotic drug. The optimal molar ratio of surfactants was determined, in order to decrease critical micellar concentration (CMC) and prepare carriers with minimal surfactant concentrations. The particle size, zeta potential, and encapsulation efficiency were determined for both pure and mixed micelles with selected composition. In vitro release kinetics of Norfloxacin from micelles show that the composition of surfactant mixture generates tunable extended release. The mixed micelles exhibit good biocompatibility against normal fibroblasts MRC-5 cells, while some cytotoxicity was found in all micellar systems at high concentrations. The influence of the surfactant components in the carrier on the antibacterial properties of Norfloxacin was investigated. The drug loaded mixed micellar formulation exhibit good activity against clinical isolated strains, compared with the CLSI recommended standard strains (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922). P. aeruginosa 5399 clinical strain shows low sensitivity to Norfloxacin in all tested micelle systems. The results suggest that Cremophor EL-Pluronic F127 mixed micelles can be considered as novel controlled release delivery systems for hydrophobic antimicrobial drugs.

Kinetics Study of Cellulose Nanocrystals Modification Using Rarasaponins by Elovich Equation

The modification of cellulose nanocrystals (CNCs) using rarasaponins (RSs) was carried out to enhancing the hydrophobicity of the CNCs. The RSs are a natural surfactant that has hydrophilic and hydrophobic sides. The linked RSs on the CNCs surface can be used to bond the hydrophobic drugs so that the modified CNCs can be applied as the hydrophobic drugs carrier in the medical field. The kinetics study was successfully carried out using the Elovich equation as the modeling equation. The Elovich equation fits the modification results well based on two parameters, i.e., the RSs/CNCs ratios and the times. The dispersion characteristics analysis was carried out to figure the enhancement of the hydrophobicity on the modified CNCs compared to the unmodified CNCs. According to the kinetics study and the dispersion characteristics analysis, the modification of CNCs using RSs could enhance CNCs utilization in the hydrophobic drug delivery system

Correlation between in vitro stability and pharmacokinetics of poly(ε-caprolactone)-based micelles loaded with a photosensitizer

Polymeric micelles are extensively investigated as drug delivery systems for hydrophobic drugs including photosensitizers (PSs). In order to benefit from micelles as targeted delivery systems for PS, rather than only solubilizers, the stability and cargo retention of the (PS-loaded) micelles should be properly assessed in biologically relevant media to get insight into the essential parameters predicting their in vivo performance (i.e., pharmacokinetics). In the present study, asymmetric flow field-flow fractionation (AF4) was used to investigate the in vitro stability in human plasma of empty and meta-tetra(hydroxyphenyl)chlorin (mTHPC)-loaded dithiolane-crosslinked micelles based on poly(ɛ-caprolactone)-co-poly(1,2-dithiolane‑carbonate)-b-poly(ethylene glycol) (p(CL-co-DTC)-PEG) and non (covalently)-crosslinked micelles composed of poly(ε-caprolactone)-b-poly(ethylene glycol) (pCL-PEG). AF4 allows separation of the micelles from plasma proteins, which showed that small non (covalently)-crosslinked pCL9-PEG (17 nm) and pCL15-PEG (22 nm) micelles had lower stability in plasma than pCL23-PEG micelles with larger size (43 nm) and higher degree of crystallinity of pCL, and had also lower stability than covalently crosslinked p(CL9-DTC3.9)-PEG and p(CL18-DTC7.5)-PEG micelles with similar small sizes (~20 nm). In addition, PS (re)distribution to specific plasma proteins was observed by AF4, giving strong indications for the (in)stability of PS-loaded micelles in plasma. Nevertheless, fluorescence spectroscopy in human plasma showed that the retention of mTHPC in non (covalently)-crosslinked but semi-crystalline pCL23-PEG micelles (>8 h) was much longer than that in covalently crosslinked p(CL18-DTC7.5)-PEG micelles (~4 h). In line with this, in vivo circulation kinetics showed that pCL23-PEG micelles loaded with mTHPC had significantly longer half-life values (t½-β of micelles and mTHPC was 14 and 18 h, respectively) than covalently crosslinked p(CL18-DTC7.5)-PEG micelles (t½-β of both micelles and mTHPC was ~2 h). As a consequence, long circulating pCL23-PEG micelles resulted in significantly higher tumor accumulation of both the micelles and loaded mTHPC as compared to short circulating p(CL18-DTC7.5)-PEG micelles. These in vivo data were in good agreement with the in vitro stability studies.In conclusion, the present study points out that AF4 and fluorescence spectroscopy are excellent tools to evaluate the (in)stability of nanoparticles in biological media and thus predict the (in)stability of drug loaded nanoparticles after i.v. administration, which is favorable to screen promising delivery systems with reduced experimental time and costs and without excessive use of animals.

Evaluation of folic acid functionalized BSA-CaFe2O4 nanohybrid carrier for the controlled delivery of natural cytotoxic drugs hesperidin and eugenol

Folic acid conjugated Bovine serum albumin-calcium ferrite nanohybrid has been synthesized and evaluated as a pH and magnetic field sensitive targeted drug delivery system for hydrophobic anticancer drugs. The receptor-targeted nanohybrid carrier was designed with smaller particle size, better stability, and magnetic susceptibility. The natural cytotoxic drugs (hesperidin and eugenol) were encapsulated in the carrier and conjugated with folic acid for targeting folate receptor over-expressed breast cancer cells. A maximum encapsulation efficiency of 62.94% and 85.58% were optimized for hesperidin and eugenol. The drug loading efficiency, stimuli responsive drug release, release kinetics and bioactivity were evaluated in-vitro, for controlled and targeted drug delivery. The carrier exhibited pH-responsive drug release with good stability at normal pH and higher release under acidic pH conditions, which can be utilized for cancer site-specific drug delivery. The presence of superparamagnetic calcium ferrite nanoparticles enabled an effective loading of drug in the carrier and an accelerated drug release under external magnetic field. The drug carrier systems were found to be highly biocompatible towards normal L929 cells. The cell viability studies on MCF-7 cell lines exhibited the enhanced cytotoxicity of hesperidin and eugenol with a 20–30 fold reduction in IC50 values, when encapsulated in folic acid conjugated BSA-calcium ferrite nanohybrid carrier, resulting from selective interaction with the receptors on breast cancer cells.

Hydrogel-based ocular drug delivery systems for hydrophobic drugs

Conventional ophthalmic dosage forms such as eye drops pose a significant challenge because physiological barriers and clearance mechanisms limit ocular bioavailability. Hydrogels are promising therapeutic materials for ocular drug delivery because of their high biocompatibility and their ability to hold and release therapeutic agents. Even though they are generally associated with the delivery of hydrophilic drugs, several approaches have been developed to integrate hydrophobic ophthalmic drugs into hydrogels. Because of the limitations associated with the traditional topical eye drop delivery of hydrophobic drugs, hydrogel-based systems represent a viable alternative for controlled ocular drug delivery. This review presents an overview on the ophthalmic applications of hydrogels for the delivery of hydrophobic drugs, with special focus on diseases occurring in the anterior segment of the eye. We summarize the key hydrogels for incorporation and delivery of hydrophobic drugs, including soft contact lenses (SCLs), stimuli-responsive hydrogels, cyclodextrin-based polymeric hydrogels, and nanoparticle-loaded hydrogels. The strategies of integrating hydrophobic drugs into hydrogels as discussed in this review provide significant potential in ocular therapeutics.

Sequential pore wall functionalization in covalent organic frameworks and application to stable camptothecin delivery systems.

Post-synthetic modification of covalent organic frameworks (COFs) is strongly demanded in order to provide additional functionalities to their structures. However, the introduction of functional groups during the synthesis of two dimensional COFs (2D COFs) is highly discouraged, as they can interfere with the π-π stacking forces, compromising framework integrity. Here, we show that direct incorporation of nucleophyllic groups (e.g., primary amines) on pore wall during the synthesis of a 2D-COF (COF-5) is possible by sequential substitution of original monomers. Subsequent bonding of the antitumor drug camptothecin results in a stable hydrophobic drug delivery system. Water adsorption isotherms modelling indicates that the insertion of CPT ligand in the framework promotes a hydrophobic effect that protects a region of COF chain from boronate ester hydrolysis and resulting degradation, which is also proven by stability testing in physiological conditions. Furthermore, this hydrophobic nature favors cell internalization kinetics by promoting interactions with the lipophilic cell membrane. To the best of our knowledge, this is the first case of a stable drug delivery system based on covalently conjugated COFs.

In vitro and in vivo evaluation ofanovel self-assembled oral delivery system for hydrophobic drugs

In vitro and in vivo evaluation ofanovel self-assembled oral delivery system for hydrophobic drugs

Preparation and Characterization of Poly(ethylene glycol)-block-Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-block-Poly(ethylene glycol) Triblock Copolymers

Amphiphilic triblock copolymers, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as a hydrophobic block and poly(ethylene glycol) (PEG) as a hydrophilic block, were successfully synthesized, with an aim to broaden the potential application of PHBV in biomedical areas. Isophorone diisocyanate having two different reactive isocyanate groups was used as the coupling agent. Telechelic hydroxylated PHBV was prepared by alcoholysis reaction, isocyanate modified and finally reacted with PEG. Molecular weight of triblock copolymer increased with the increasing molecular weight of PHBV-diol and PEG. The length of the PHBV block and PEG block had a great influence on the crystallization behavior of the triblock copolymers. Thermal degradation temperature of PHBV segment enhanced greatly. The triblock copolymer showed a tendency toward formation of aggregation in aqueous solution with a critical aggregation concentration of 5.01×10-4 g·L-1, and the rod-shape assembly with a uniform hydrophilic shell might be employed as hydrophobic drug delivery systems.

Construction of an environmentally friendly octenylsuccinic anhydride modified pH-sensitive chitosan nanoparticle drug delivery system to alleviate inflammation and oxidative stress

An environmentally friendly octenylsuccinic anhydride modified pH-sensitive chitosan-octenylsuccinic anhydride (OSA-CS) was synthesized. The critical micelle concentration (CMC) of the modified chitosan was 27 μg/mL, the graft polymers can form solubilized curcumin (CUR) and quercetin (QUE) nanoparticles. The drug-loaded nanoparticles had high encapsulation efficiency and drug loading content, the self-assembly of graft polymers formed spherical uniform nanoparticles with an approximate diameter of 150–180 nm. The nanoparticles were stable under storage conditions and in serum. The results revealed that OSA-CS exhibited excellent biocompatibility, no cytotoxicity. Additionally, the results of pH sensitivity and drug release experiments showed that the nanoparticles were highly sensitive to weakly acidic conditions (pH 6.0) and showed a faster release rate, while they were reasonably stable at physiological conditions (pH 7.4). The drug-loaded nanoparticles exhibited higher cellular uptake in vitro, and exhibited stronger anti-inflammatory and antioxidant efficacy. Therefore, OSA-CS-based nanoparticles are a promising hydrophobic drug delivery system for pH-response targeting therapy.

Fabrication and performance of a spherical cellulose nanocrystal-based hydrophobic drug delivery vehicle using rubber wood

Cellulose nanocrystals (CNCs) were fabricated using rubber wood (RW) as the raw material via acid hydrolysis followed by ultrasonication. The CNCs samples were then grafted with succinic anhydride to obtain modified CNCs, hereafter called CS. The CS samples were subsequently coated with a cationic surfactant, cetyltrimethyl ammonium bromide, and the obtained samples were named as CC. The morphology, chemical structure, and thermal stability of the RW, CNCs, CS, and CC samples were characterized using transmission electron microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis, respectively. Finally, the drug release performance was investigated using CC as the drug carrier and hesperidin, a hydrophobic drug, as the model drug. The drug release mechanism was also considered. The results of this study identified a new route for the high-value utilization of RW and also demonstrated that RW could be used as a novel substrate for the construction of cellulose-based hydrophobic drug delivery systems.

<p>Elaboration and characterization of curcumin-loaded Tri-CL-mPEG three-arm copolymeric nanoparticles by a microchannel technology</p>

Purpose: Clinical applications of curcumin (Cur) have been greatly restricted due to its low solubility and poor systemic bioavailability. Three-arm amphiphilic copolymer tricarballylic acid-poly (ε-caprolactone)-methoxypolyethylene glycol (Tri-CL-mPEG) nanoparticles (NPs) were designed to improve the solubility and bioavailability of Cur. The present study adopted a microchannel system to precisely control the preparation of self-assembly polymeric NPs via liquid flow-focusing and gas displacing method.Methods: The amphiphilic three-arm copolymer Tri-CL-mPEG was synthesized and self-assembled into nearly spherical NPs, yielding Cur encapsulated into NP cores (Cur-NPs). The obtained NPs were evaluated for physicochemical properties, morphology, toxicity, cellular uptake by A549 cells, release in vitro, biodistribution, and pharmacokinetics in vivo.Results: Rapidly fabricated and isodispersed Cur-NPs prepared by this method had an average diameter of 116±3 nm and a polydispersity index of 0.197±0.008. The drug loading capacity and entrapment efficiency of Cur-NPs were 5.58±0.23% and 91.42±0.39%, respectively. In vitro release experiments showed sustained release of Cur, with cumulative release values of 40.1% and 66.1% at pH 7.4 and pH 5.0, respectively, after 10 days post-incubation. The results of cellular uptake, biodistribution, and in vivo pharmacokinetics experiments demonstrated that Cur-NPs exhibited better biocompatibility and bioavailability, while additionally enabling greater cellular uptake and prolonged circulation with possible spleen, lung, and kidney targeting effects when compared to the properties of free Cur.Conclusion: These results indicate that Tri-CL-mPEG NPs are promising in clinical applications as a controllable delivery system for hydrophobic drugs.

An Overview of Nanogel –Novel Drug Delivery System

Nanogels are innovative drug delivery system that can play an integral part in pointing out many issues related to old and modern courses of treatment such as nonspecific effects and poor stability. Biomedical and pharmaceutical applications of Nanogels have been explored for tissue regeneration, wound healing, surgical device, implantation, and peroral, rectal, vaginal, ocular, and transdermal drug delivery. Nanogels are proficiently internalized by the target cells, avoid accumulating in nontarget tissues thereby lower the therapeutic dosage and minimize harmful side effects. Nanogels may be defined as highly cross linked nano-sized hydrogels ranges from 20-200 nm. They can be administered through various routes, including oral, pulmonary, nasal, parenteral, intra-ocular etc. They have a high degree of drug loading capacity and it shows better permeation capabilities due to smaller size. Nanogels are the novel drug delivery systems for both hydrophilic and hydrophobic drugs.

Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery.

Hydrophobic drugs, such as methotrexate, are not easily delivered into the human body. Therefore, the use of amphiphilic nanoplatforms to the transport of these drugs through the bloodstream is a challenge. While the hydrophobic region interacts with the drug, the hydrophilic outer layer enhances its bioavailability and circulation time. Poly (ethylene glycol)-block-poly(ε-caprolactone) PEG-b-PCL micelles are biodegradable and biocompatible, allowing its use as a nanocarrier for drug delivery systems. The stealth property of PEG that composes the outer layer of nanoplatforms, makes the micelle unperceivable to phagocytic cells, increasing the circulation time in the human body. In addition, folic acid functionalization enables micelle selectively targeting to cancer cells, improving treatment efficiency and reducing side effects. In this work, PEG-b-PCL copolymer was synthesized by ring opening polymerization (ROP) of the ε-caprolactone with Poly(ethylene glycol) as a macroinitiator and tin(II) 2-ethyl hexanoate as a catalyst. Functionalization of such micelles with folic acid occurred through the modification of the PEG terminal group. The surface modification of the copolymer micelles resulted in higher critical micellar concentration (CMC), increasing approximately 100 times. The synthesis of the copolymers resulted in molecular weight around 3000 g mol-1 with low polydispersity. The polymer micelles have a hydrodynamic diameter in the range of 100-200 nm and the functionalized sample doesn't show aggregation in the considered pH range. High incorporation efficiency was obtained with a minimum percentage of 85%. The drug release profile and linearization from the Peppas model confirmed the interaction of methotrexate with the hydrophobic segment of the copolymer and its release mechanism by relaxation and/or degradation of the chains, making PEG-b-PCL micelles suitable candidates for hydrophobic drug delivery systems.

Poly(methyl vinyl ether-co-maleic acid) Hydrogels Containing Cyclodextrins and Tween 85 for Potential Application as Hydrophobic Drug Delivery Systems

Hydrogels have been extensively investigated as a platform for drug delivery. However, their use for the delivery of hydrophobic drugs has been limited by their incompatibility with hydrophobic drug molecules. The chemical modification of the structure of the hydrogels to include hydrophobic moieties has been proven to be a good alternative to increase the stability and solubility of hydrophobic drugs in the polymer matrix of the hydrogel. The inclusion of hydroxypropyl-β-cyclodextrins (HPBCD) and Tween® 85 (T85) within hydrogel matrices has the potential to improve hydrophobic drug loading and release. HPBCD have the ability to host hydrophobic drug molecules in their cone-like structure, forming inclusion complexes through host-guest interactions. On the other hand, T85 is an amphiphilic molecule and, consequently, has the potential to increase hydrophilic drug loading within the hydrogels. In the present work, a new type of hydrogel made from poly(methyl vinyl ether-co-maleic acid) (GAN) and poly(ethylene glycol) (PEG) containing T85 and HPBCD was synthesized for hydrophobic drug release. Hydrogels were based on GAN crosslinked (PEG) and HPBCD and/or T85 via an esterification in the solid state (solvent free). The synthesised hydrogels were characterised using Fourier transform infrared (FTIR) spectroscopy, swelling studies and contact angle measurements. The hydrogels showed swellings ranging from 140 to 180%. The inclusion of T85 in the hydrogels improved the wettability of the materials. On the other hand, the inclusion of HPBCD within the hydrogels decreased the wettability as the contact angle between the hydrogels and water increased with the HPBCD content. Finally, the materials were loaded with an ophthalmic drug, dexamethasone (DX). HPBC-containing hydrogels showed a higher DX uptake and, consequently, also a higher capacity of DX release. On the other hand, T85 containing hydrogels did not show any improvement over the hydrogels containing only GAN and PEG. The hydrogels were able to provide sustained DX release over periods of 6 h.

Facile preparation of metal−organic frameworks-based hydrophobic anticancer drug delivery nanoplatform for targeted and enhanced cancer treatment

Nowadays, cancer has been one of the major threats to human beings throughout the world. Nanomedicines have been demonstrated as a promising candidate for cancer chemotherapy. In this work, we facilely constructed a RGD (Arg-Gly-Asp) modified camptothecin@zeolitic imidazolate framework-8 (RGD@CPT@ZIF-8) as a novel metal-organic frameworks-based hydrophobic drug delivery system for targeted and enhanced cancer treatment. In our system, the nanoplatform exhibited the superior property of target to the cancer cells due to the function with RGD. More importantly, the RGD@CPT@ZIF-8 nanoplatform has shown the enhanced cancer cell treatment due to the excellent pH-responsive hydrophobic anticancer drug delivery and intracellular ROS generation. With the excellent targeting and enhanced therapy performance, we envision that the hydrophobic anticancer drug delivery system could become a potential therapeutic agent for targeted cancer treatment.

Co-delivery of siRNA and etoposide to cancer cells using an MDEA esterquat based drug delivery system

Cancer has become the leading cause of death in many countries. Chemotherapy is a key component in the treatment of most cancers but has limited efficacy if the cancer develops resistance to the treatment over time and recur. RNA interference may be used to reduce the production of the proteins responsible for chemotherapeutic resistance. Small interfering RNAs (siRNA) may be used to induce RNA interference but the application of these to cancer cells is hampered by poor serum stability and delivery to their cytoplasmic site of activity.This work introduces a novel nanoparticle delivery system for siRNA and hydrophobic anticancer drugs. The system is based on a cationic MDEA esterquat, which is widely and safely used in personal care products but has never been assessed for drug delivery applications. We show that MDEA forms spherical compact nanoparticles when combined with siRNA that delivers the siRNA to cancer cells where it induces gene silencing. By combining DOPE and MDEA in ratios of 2:1 and 3:1, even higher gene silencing levels (>90%) may be achieved. The system is capable of combinational therapy by co-delivering siRNA and the chemotherapeutic drug etoposide to cancer cells and these particles both induce gene silencing and chemotherapy induced cell death. We believe the present system may be used for intra-tumoral injection of chemotherapy in solid chemotherapy resistant tumors and for systemic delivery with further development.

MPEG-co-PCL nanoparticles: The influence of hydrophobic segment on methotrexate drug delivery

The use of drug delivery system based on polymeric nanoparticles (PNP) has been investigated due to its capacity to carrier hydrophobic drugs across natural barriers and to access new sites in the human body to release drugs at different tissues or cells. In the present work, polyethylene glycol monomethyl ether – co – polycaprolactone copolymer (mPEG-co-PCL) was synthesized by ring opening polymerization of the ε-caprolactone in the presence of polyethylene glycol monomethyl ether (mPEG) as a macroinitiator and tin(II) 2-ethylhexanoate (Sn (Oct)2), as a catalyst. On this step, three syntheses were realized to increase the polycaprolactone (PCL) hydrophobic segment of the copolymer. PNP of mPEG-co-PCL were obtained by emulsion – solvent evaporation method, which the surfactant concentration (Tween80®), cosurfactant (dodecane) and water/oil ratio were studied to control the size of nanoparticles. The PNP ability to loading and releasing drugs was evaluated with methotrexate (MTX), a drug commonly used for cancer treatment. The copolymers were synthesized with different chain length, increasing PCL hydrophobic segment, resulting in molecular weight between 2,000 to 13,000 g mol−1. The lowest hydrodynamic diameter (79.5 nm) of PNP was obtained with a solution of 1 × 10-4 mol L−1 Tween80® solution and 500 u L of dodecane. The water/oil ratio showed insignificant influence on hydrodynamic diameter, according to factorial design results. The copolymers showed a loading efficiency of MTX higher than 80.0%. The MTX releases from mPEG-co-PCL platform had occurred by anomalous transport mechanism in the first hours. After 16 h the release rate of MTX decrease drastically and its behavior was governed by PCL degradation process. As PCL ratio is increased on copolymer, the drug release decrease, suggesting an interaction of MTX with PNP hydrophobic segment. Thus, the MTX release could be controlled by copolymer chain length through hydrophilic and hydrophobic segment composition ratio, being a good candidate for hydrophobic drug delivery systems.