Hyaluronic Acid Graft Research Articles

Macrophage proteomic analysis of covalent immobilization of hyaluronic acid and graphene oxide on CoCr alloy in a tribocorrosive environment.

In this work, a sequential covalent immobilization of graphene oxide (GO) and hyaluronic acid (HA) is performed to obtain a biocompatible wear-resistant nanocoating on the surface of the biomedical grade cobalt-chrome (CoCr) alloy. Nanocoated CoCr surfaces were characterized by Raman spectroscopy and electrochemical impedance spectroscopy (EIS) in 3 g/L HA electrolyte. Tribocorrosion tests of the nanocoated CoCr surfaces were carried out in a pin on flat tribometer. The biological response of covalently HA/GO biofunctionalized CoCr surfaces with and without wear-corrosion processes was studied through the analysis of the proteome of macrophages. Raman spectra revealed characteristic bands of GO and HA on the functionalized CoCr surfaces. The electrochemical response by EIS showed a stable and protective behavior over 23 days in the simulated biological environment. HA/GO covalently immobilized on CoCr alloy is able to protect the surface and reduce the wear volume released under tribocorrosion tests. Unsupervised classification analysis of the macrophage proteome via hierarchical clustering and principal component analysis (PCA) revealed that the covalent functionalization on CoCr enhances the macrophage biocompatibility in vitro. On the other hand, disruption of the HA/GO nanocoating by tribocorrosion processes induced a macrophage proteome which was differently clustered and was distantly located in the PCA space. In addition, tribocorrosion induced an increase in the percentage of upregulated and downregulated proteins in the macrophage proteome, revealing that disruption of the covalent nanocoating impacts the macrophage proteome. Although macrophage inflammation induced by tribocorrosion of HA/GO/CoCr surfaces is observed, it is ameliorated by the covalently grafting of HA, which provides immunomodulation by eliciting downregulations in characteristic pro-inflammatory signaling involved in inflammation and aseptic loosening of CoCr joint arthroplasties. Covalent HA/GO nanocoating on CoCr provides potential applications for in vivo joint prostheses led a reduced metal-induced inflammation and degradation by wear-corrosion.

Modification of poly(styrene‐b‐isobutylene‐b‐styrene) using hyaluronic acid via surface graft polymerization and cytotoxicity investigation

AbstractPoly(styrene‐b‐isobutylene‐b‐styrene) (SIBS) is a biomedical elastomer with excellent overall properties. However, the low surface energy and the surface hydrophobicity of SIBS have limited its application as a human implantable material. To improve its biocompatibility, in this work, hyaluronic acid (HA) was introduced onto the surface of SIBS. Firstly, glycidyl methacrylate (GMA) and HA were employed to prepare GMA‐modified HA (GMHA) via grafting reaction. Due to the introduction of carbon–carbon double bonds on the side chain of HA, the GMHA could be used for free radical polymerization between SIBS. The effects of UV illumination time, GMHA concentration, and initiator concentration on the grafting ratio were investigated. FTIR, 1H NMR, and XPS confirmed the successful grafting of HA onto SIBS. The experimental results showed that the surface modification method not only ensured that the excellent properties of the SIBS would not be destroyed but also improved its surface properties successfully. Besides, the MTT assay indicated that the GMHA‐modified SIBS was not bio‐toxic, so it could meet the need to expand its use in the biomedical fields.

Glycocalyx-inspired dynamic antifouling surfaces for temporary intravascular devices

Protein and cell adhesion on temporary intravascular devices can lead to thrombosis and tissue embedment, significantly increasing complications and device retrieval difficulties. Here, we propose an endothelial glycocalyx-inspired dynamic antifouling surface strategy for indwelling catheters and retrievable vascular filters to prevent thrombosis and suppress intimal embedment. This strategy is realized on the surfaces of substrates by the intensely dense grafting of hydrolyzable endothelial polysaccharide hyaluronic acid (HA), assisted by an amine-rich phenol-polyamine universal platform. The resultant super-hydrophilic surface exhibits potent antifouling property against proteins and cells. Additionally, the HA hydrolysis induces continuous degradation of the coating, enabling removal of inevitable biofouling on the surface. Moreover, the dense grafting of HA also ensures the medium-term effectiveness of this dynamic antifouling surface. The coated catheters maintain a superior anti-thrombosis capacity in ex vivo blood circulation after 30 days immersion. In the abdominal veins of rats, the coated implants show inhibitory effects on intimal embedment up to 2 months. Overall, we envision that this glycocalyx-inspired dynamic antifouling surface strategy could be a promising surface engineering technology for temporary intravascular devices.

Injection Treatments for Vulvovaginal Atrophy of Menopause: A Systematic Review.

Injection treatments have been proposed as novel treatment options for Vulvovaginal Atrophy of Menopause (VVA) also known as Genitourinary Syndrome of Menopause (GSM). However, to date data about these treatments are poor. To assess all available injection treatments for VVA. A systematic review was performed by searching five electronic databases for peer-reviewed studies that assessed injection treatments for VVA. Eight studies (7 observational and 1 randomized) with 236 women were included. Assessed injection materials were: autologous platelet-rich plasma (PRP) + hyaluronic acid (HA), not cross-linked HA plus calcium hydroxyapatite (NCLHA + CaHA), micro-fragmented adipose tissue (MFAT), hyaluronan hybrid cooperative complexes (HCC), crosslinked HA, microfat and nanofat grafting + PRP, and PRP alone. Improvement in GSM symptoms after treatment was assessed through Visual Analogic Scale (VAS) for GSM symptoms or patient satisfaction, several validated questionnaires (FSFI, VHI, FSD, SF12, ICIQ UI SF, PGI-I, FSDS-R, VSQ), symptoms severity, changes in vaginal mucosa thickness, flora, pH, and expression on vaginal mucosal biopsies of Procollagen I and III and ki67 immunofluorescence or COL1A1 and COL3A1 mRNA. Injection treatments showing significant improvement in GSM-related symptoms were: (i) HCC in terms of VAS for GSM symptoms and FSFI score; (ii) Crosslinked HA in terms of VAS for GSM symptoms, FSFI and VHI score, COL1A1 and COL3A1 mRNA expression on vaginal mucosal biopsies; (iii) NCLHA + CaHA in terms of FSFI score; (iv) PRP + HA in terms of VHI, FSD and SF12 score; (v) microfat and nanofat grafting + PRP in terms of VHI score and FSDS-R score; (vi) PRP alone in terms of VHI and VSQ scores. All assessed injection treatments except for MFAT seem to lead to significant improvement in VVA symptoms on validated questionnaires. Further studies are necessary in the field. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A snowboard-inspired lubricating nanosystem with responsive drug release for osteoarthritis therapy

Most of present works of osteoarthritis (OA) therapy are focusing on reducing friction and improving drug loading capacity, while little attention is paid to realizing long-time lubrication and on-demand drug release. In this study, inspired by snowboards with good solid–liquid interface lubrication, a fluorinated graphene based nanosystem with dual functions of long-time lubrication and thermal-responsive drug release was constructed for OA synergetic therapy. An aminated polyethylene glycol bridging strategy was developed to enable covalent grafting of hyaluronic acid on fluorinated graphene. This design not only greatly increased the nanosystem’s biocompatibility, but also reduced the coefficient of friction (COF) by 83.3 % compared to H2O. The nanosystem showed long-time and steady aqueous lubrication behavior even after more than 24,000 times of friction tests, and a low COF of 0.13 was obtained with over 90% wear volume reduction. Diclofenac sodium was controllably loaded and sustained drug release was tuned by near-infrared light. Moreover, anti-inflammation results showed that the nanosystem had good protective effect on inhibiting OA deterioration, which could up-regulate cartilage anabolic genes of Col2α and aggrecan while down-regulating catabolic proteases genes of TAC1 and MMP1. This work constructs a novel dual-functional nanosystem that realizes friction and wear reduction with long lubrication life, and shows thermal-responsive on-demand drug release with good synergistic therapeutic effect of OA.

A Biomimetic Lubricating Nanosystem with Responsive Drug Release for Osteoarthritis Synergistic Therapy.

Osteoarthritis (OA) is associated with lubrication failure of articular cartilage and severe inflammatory response of joint capsule. Synergistic therapy combining joint lubrication and anti-inflammation emerges as a novel treatment of OA. In this study, bioinspired by ultralow friction of natural articular synovial fluid and mussel adhesion chemistry, a biomimetic nanosystem with dual functions of enhanced lubrication and stimuli-responsive drug release is developed. A dopamine mediated strategy realizes one step biomimetic grafting of hyaluronic acid (HA) on fluorinated graphene. The polymer modified sheets exhibit highly efficient near-infrared absorption, and show steady lubrication with a longtime under various working conditions, in which the coefficient of friction is reduced by 75% compared to H2 O. Diclofenac sodium (DS) with a high loading capacity of 29.2% is controllably loaded, and responsive and sustained drug release is adjusted by near-infrared light. Cell experiments reveal that the lubricating nanosystem is taken up by endocytosis, and anti-inflammation results confirm that the nanosystem inhibits osteoarthritis deterioration by upregulating cartilage anabolic gene and downregulating catabolic proteases and pain-related gene. This work proposes a promising biomimetic approach to integrate polymer modified fluorinated graphene as a dual-functional nanosystem for effective synergistic therapy of OA.

Hyaluronic Acid-Enwrapped Polyoxometalate Complex for Synergistic Near Infrared-II Photothermal/Chemo-Therapy and Chemodynamic Therapy.

To enhance the efficacy of tumor therapy, the collection of functional components into a targeting system shows advantages over most homogeneous materials in inducing apoptosis of cancer cells. The security and targeting of therapeutic agents also require the effect combination of additional components. However, the construction of multifunctional composites in a simple system with intelligent cooperative responsiveness remains a challenge. Herein, a reduced polyanionic cluster (rP2W18) bearing the absorption at the near infrared (NIR) II region is used as a core carrier to bind the positively charged doxorubicin hydrochloride (DOX) through ionic interaction. To reduce the physiological toxicity, hyaluronic acid grafting β-cyclodextrin side chains is used to cover the ionic complex through host-guest inclusion to DOX. When the nanocomposite is activated by local laser exposure, the final three-component therapeutic agent is demonstrated to present targeted photothermal conversion capability and chemodynamic activity together with chemotherapy. With the controlled release of DOX under the stimulation of mild acidity in the tumor region and photothermal effect, the exposed rP2W18 is aroused by hydrogen peroxide overexpressed in a tumor microenvironment to produce toxic reactive oxygen species, 1O2. This work presents an opportunity for the development of a nanocomposite in NIR-II photothermal/chemo-therapy and chemodynamic synergistic therapy.

The effect of 3-D printed polylactic acid scaffold with and without hyaluronic acid on bone regeneration.

Three- dimensional (3D) technology has been suggested to overcome several limitations in guided bone regeneration (GBR) procedures because 3D-printed scaffolds can be easily molded to patient-specific bone defect site. This study aimed to investigate the effect of 3-D printed polylactic acid (PLA) scaffolds with or without hyaluronic acid (HA) in a rabbit calvaria model. A calvaria defect with a diameter of 15mm was created in 30 New Zealand white rabbits. The rabbits were randomly allocated into three groups including no graft group (control, n=10), 3D printed PLA graft group (3D-PLA, n=10), and 3D printed PLA with hyaluronic acid graft group (3D-PLA/HA, n=10). Five animals in each group were sacrificed at 4 and 12weeks after surgery. Microcomputed tomography and histologic and histomorphometric analyses were performed. Over the whole examination period, no significant adverse reactions were observed. There were no statistically significant differences in bone volume (BV) /tissue volume (TV) among the three groups at 4weeks. However, the highest BV/TV was observed in the 3D-PLA/HA group at 12weeks. The new bone area for control, 3D-PLA, and 3D-PLA/HA showed no statistical differences at 4weeks. However, the value was significantly higher in the 3D-PLA and 3D-PLA/HA groups compared to the control group at 12weeks. The 3D printed PLA scaffolds was biocompatible and integrated well with bone defect margin. They were also provided the proper space for new bone formation. Therefore, 3D printed PLA/HA might be a potential tool to enhance bone augmentation.

Functionalized GO Nanovehicles with Nitric Oxide Release and Photothermal Activity-Based Hydrogels for Bacteria-Infected Wound Healing.

Bacteria-infected wounds are attracting increasing attention, as antibiotic misuse and multidrug-resistant bacteria complicate their treatment. Herein, we reported a photothermal activity-based drug consisting of β-cyclodextrin (βCD)-functionalized graphene oxide (GO) near-infrared light-responsive nanovehicles combined with the nitric oxide donor BNN6, in a methacrylate-modified gelatin (GelMA)/hyaluronic acid graft dopamine (HA-DA) hydrogel. The synergistic effects of photothermal and gas therapies are expected to improve antibacterial efficiency and reduce drug resistance. The results revealed that GelMA/HA-DA/GO-βCD-BNN6 was an ideal antibacterial material that improved collagen deposition and angiogenesis and promoted wound healing in a mouse model of full-thickness skin repair, compared to the commercially available Aquacel Ag dressing. We developed a multifunctional nanocomposite hydrogel that exhibited antibacterial and angiogenic properties, adhesiveness, and mechanical properties that enhance the regeneration of bacteria-infected wounds.

Grafting of Hyaluronic Acid to PLDLA, used as coating of the models of PLLA bioresorbable coronary stents

Coronary artery disease has been leading cause of death in the world, angioplasty stent implantation is an important strategy in these cases. Studies indicate that biodegradability, immobilization of antiproliferatives and bioactive molecules in stents, are the characteristics of future generations of these devices. Amongst them, hyaluronic acid contributes to decrease of the aggregation and proliferation of cells between artery layers and the implanted device. For this purpose, poly (L-lactic acid) (PLLA) bioresorbable coronary stents with hyaluronic acid (HA) grafting in poly (LD- lactic acid) (PLDLA) were developed. The models were characterized as their thermal properties with Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetric Analysis (DSC), Fourier Transform Infrared Spectrometry (FTIR), Wettability, with study of Contact Angle using Water swelling. PLDLA ADH-modified HA grafting presented more hydrophilic surface characteristics, ideal for coating material of this devices. In conclusion, grafting of hyaluronic acid in the PLDLA matrices confirmed, by technics used at this project. The coating of models of PLLA with PLDLA-HAADH made by dip coating technic.

A dual responsive hyaluronic acid graft poly(ionic liquid) block copolymer micelle for an efficient CD44-targeted antitumor drug delivery

Illustration of the formation and elevated antitumor mechanism of the HA-g-mPEG-polymers nanocarriers.

Hyaluronic Acid and Chitosan Surface Grafted Polylactide Single Crystals as Hydrophilic Building Blocks for Scaffold Materials

Polylactide has a well-known biocompatibility and processability, but its surface hydrophobicity could limit their use as a proper scaffold for cell growth and proliferation. The present work aims to fabricate the polylactide scaffolds by a bottom-up approach from pre-modified building blocks as an efficient way to overcome such a challenge and to provide a surface with a spatially organized chemical structure. Pre-modified polylactide single crystals (PLLAsc) with chitosan or hyaluronic acid, which are hydrophilic and bioactive macromolecules, were assembled into three-dimensional scaffolds. PLLAsc were hydrolyzed to introduce carboxylic groups at the surface and then the grafting reactions were carried out by carbodiimide chemistry. Although chitosan was grafted directly, the hydrolyzed surface was endowed with adipic acid dihydrazide as a spacer before hyaluronic acid grafting. The analyses of the modified surfaces verified the enhancement in surface hydrophilicity without any drastic effects on single crystals properties. By fabricating the scaffolds by using a compression molding salt leaching technique in the absence of heat or gluing materials, they were found to have an open interconnected structure, a hydrophilic surface and sustainable mechanical properties. Biological activity of scaffolds was examined by using mouse fibroblasts. Scaffolds having hyaluronic acid and chitosan surface grafted PLLAsc showed better interface for cell growth than pristine ones. Obviously, prefunctionalized PLLAsc with biomacromolecules could be used as proper building blocks for designing polymer scaffolds.

A nonfouling voltammetric immunosensor for the carcinoembryonic antigen based on the use of polyaniline nanowires wrapped with hyaluronic acid.

A non-fouling electrochemical immunosensor is described for determination of the tumor biomarker carcinoembryonic antigen (CEA). It is based on the use of composite wires made by chemical grafting of hyaluronic acid onto polyaniline nanowires. The modified nanowires possess excellent antifouling property both in single protein solutions and in dilute serum samples. The current of immunoelectrode exhibits a linear response in the 0.01pgmL-1 to 10,000pgmL-1 CEA concentration range and 0.0075pgmL-1 detection limit. This work demonstrates that coating an electrode with hyaluronic acid can largely reduce unspecific adsorption of proteins on the electrode surface. Graphical abstract Schematic of a nonfouling electrochemical immunosensor for the carcinoembryonic antigen. It is based on novel composite wires made through the chemical grafting of easily available hyaluronic acid (HA) onto polyaniline (PANI) nanowires. The HA/PANI demonstrated excellent antifouling property both in single protein solutions and human serum samples.

Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures.

Design, characterization and optimization of lamivudine-loaded amphiphilic HA-g-ECL nanoparticles

This investigation sought to engineer and optimize a novel Lamivudine (LMV)-loaded nanoformulation through grafting of hyaluronic acid (HA) and epsilon-caprolactam (ECL) (HA-g-ECL) for potentially enhanced treatment of Hepatitis B Virus (HBV) infection. The HA-g-ECL copolymer and subsequently its nanoparticles were prepared by anionic graft copolymerization, and a double emulsion solvent-evaporation method, respectively. Verification of grafting of the novel amphiphilic copolymer was via analysis of the vibrational, thermal and rheological transitions of HA-g-ECL, as well as demonstration of a critical micelle concentration (CMC). A Box-Behnken experimental design was applied to generate 15 nanoparticulate formulations, which were evaluated for their physicochemical properties, including mean particle size, morphology, drug entrapment efficiency (DEE), and drug release characteristics (MDT). There was a significant interaction effect on the MDT between the level of copolymer and surfactant (p = 0.008). Approximately 65% LMV was released in the first 15 h for design formulations comprising lower levels of HA-g-ECL, while ∼20% LMV was released with higher levels of HA-g-ECL. Varying the quantities of copolymer, surfactant and solvent thus had notable implications in controlling the drug entrapment efficiency and release from the copolymeric system. The optimized nanoparticulate system demonstrates potential for the controlled delivery of LMV for treatment of HBV infection.

"Click" Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve Lens Wettability and Lower Protein Adsorption.

Improving the wettability of and reducing the protein adsorption to contact lenses may be beneficial for improving wearer comfort. Herein, we describe a simple "click" chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate naturally contributing to the wettability of the native tear film. A two-step preparation technique consisting of laccase/TEMPO-mediated oxidation followed by covalent grafting of hydrazide-functionalized HA via simple immersion resulted in a model lens surface that is significantly more wettable, more water retentive, and less protein binding than unmodified pHEMA while maintaining the favorable transparency, refractive, and mechanical properties of a native lens. The dipping/coating method we developed to covalently tether the HA wetting agent is simple, readily scalable, and a highly efficient route for contact lens modification.

Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer.

This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect.

Surface engineered nanostructured lipid carriers for targeting MDR tumor: Part II. In vivo biodistribution, pharmacodynamic and hematological toxicity studies

Irinotecan loaded nanostructured lipid carrier (NLC-Ir) was surface decorated with hyaluronic acid graft polymer. Hyaluronic acid is a biocompatible, non-antigenic and hydrophilic, CD-44 ligand that can impart many useful features to the nanocarrier for anticancer drug delivery. The present investigation demonstrated that hyaluronic acid coated HA-NLC had significantly lower haemolytic potential as compared to uncoated NLC. Further, HA-NLC had a reduced plasma protein interaction and low macrophage uptake. The in vivo tumor targeting and pharmacodynamics efficacy of HA-NLC was studied in Ehrlich's Ascites Tumor (EAT) allograft model. Radio scintigraphic biodistribution studies revealed that HA-NLC carrier got accumulated in the tumor tissues in good proportion. Additionally, the content of radioactivity associated with tumor tissues remained constant at 2, 4 and 24h (2.41, 2.48 and 2.47%, respectively), while it got reduced in other organs. Furthermore, tumor to muscle ratio of radioactivity suggested a better accumulation of HA-NLC in tumor tissues that was significantly enhanced (P<0.05) with time. In vivo antitumor activity of hyaluronan coated HA-NLC-Ir was 5.8 and 2.6 times higher as compared to control and free drug solution respectively. Furthermore, encapsulation of irinotecan in HA-NLC-Ir nanocarrier was found to have reduced the thrombocytopenia and neutropenia associated with free irinotecan. Thus, it can be inferred that the hyaluronic acid decorated nanocarrier can provide a haemo-compatible, non-toxic and target based delivery system for the effective management of cancer.

Cell‐adhesive thermogelling PNIPAAm/hyaluronic acid cell delivery hydrogels for potential application as minimally invasive retinal therapeutics

Copolymers of N-isopropylacrylamide (NIPAAm) and acrylic acid N-hydroxysuccinimide (NAS) were synthesized via free radical polymerization and conjugated with amine-functionalized hyaluronic acid (HA) and cell adhesive RGDS peptides. These novel copolymers were designed to facilitate noninvasive delivery of a liquid suspension of cells into the delicate subretinal space for treatment of retinal degenerative diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. The various synthesized copolymers all displayed subphysiological phase transition temperatures, thereby allowing temperature-induced scaffold formation and subsequent entrapment of transplanted cells within an adhesive support matrix. Successful grafting of HA and RGDS peptides were confirmed with Fourier Transform Infrared (FTIR) spectroscopy and quantified with (1)H Nuclear Magnetic Resonance (NMR) spectroscopy. All copolymers demonstrated excellent compatibility with retinal pigment epithelial (RPE) cells in culture and minimal host response was observed following subcutaneous implantation into hairless SKH1-E mice (strain code 447).

Self-assembled amphiphilic hyaluronic acid graft copolymers for targeted release of antitumoral drug

Polymeric micelles obtained by self-assembling of amphiphilic hyaluronic acid (HA) graft copolymers have been prepared and characterized. In particular, hyaluronic acid (HA) has been grafted to polylactic acid (PLA) and polyethylenglycol chains (PEG), then the copolymers able to form micelles in aqueous medium have been chosen to entrap the antitumoral drug Doxorubicin. The critical aggregation concentration of HA-g-PLA or HA-g-PLA-g-PEG micelles has been determined by using pyrene as a fluorescent probe, whereas their shape and size have been evaluated by light scattering measurements, scanning and transmission electron microscopies. The selective cytotoxicity of drug loaded micelles toward the CD-44 over-expressing HCT-116 cells compared to receptor deficient human derm fibroblasts has been demonstrated. Pegylated micelles showed better stability and drug loading capacity and they were able to escape from macrophage phagocytosis.