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1.
Ann Jt ; 9: 18, 2024.
Article in English | MEDLINE | ID: mdl-38690078

ABSTRACT

Background and Objective: Femoral bone defect in hip arthroplasty revision surgery represents a complex problem, and the treatment is a challenge for orthopedic surgeons called to assess the residual bone stock in an altered anatomy and obtain stability for the new implant. Classification systems available are mostly based on X-rays two-dimensional images and lack of accuracy and reproducibility and comprehensive therapeutic algorithms. However, there is no record of any classification based on computed tomography (CT)-scan images or three-dimensional (3D) modeling modern techniques. We aimed to review the current literature around femoral defect classifications (FDCs) analyzing their different rationale basis, reliability and accuracy, and their benefit in clinical practice. Moreover, we highlighted the role of CT scan-based 3D modeling techniques in the setting of femoral bone defects and revision hip arthroplasty. Methods: A narrative review was conducted. The articles were selected from the PubMed and Scopus medical database updated to March 2023. All Level-I to IV studies in the English language were considered for inclusion. The research was performed using relevant search term items: "femoral defects", "classification", "radiographic", "revision hip arthroplasty", "CT scan" and "3D" and we included only articles that evaluated the accuracy or reliability (or both) of the different femoral bone defects classification system. Key Content and Findings: Our search yielded 408 results, of which 17 were deemed highly relevant. We found seven X-ray-based classification systems which have been attempted to quantify the degree of bone loss with low to good reproducibility. The most used classification system for femoral bone defects were the AAOS and Paprosky classification, which also offers a clinical therapeutic algorithm. In 2021, the FDC interestingly showed a new simple classification system with sub-optimal reproducibility and a practical therapeutic algorithm. Despite the numerous classification system of femoral defects, none of them comprehends the use of CT scan and 3D imaging technologies. Conclusions: Traditional X-rays-based classification system are still widely used event if their intra-observer and inter-observer reliability is sub-optimal. 3D modeling techniques represent an important diagnostic tool that could improve the understanding of bone defects and residual bone supportive structures, allowing to elaborate new, more precise, classification systems.

2.
J Gastrointest Surg ; 28(7): 1185-1193, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38599315

ABSTRACT

BACKGROUND: Peritoneal carcinomatosis significantly worsens the prognosis of patients with gastric cancer. Cytoreduction + hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in the prevention and treatment of peritoneal carcinomatosis in advanced gastric cancer (AGC); however, its application remains controversial owing to the variability of the approaches used to perform it and the lack of high-quality evidence. This systematic review and meta-analysis aimed to investigate the role of surgery and HIPEC in the prevention and treatment of peritoneal carcinomatosis of gastric origin. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing surgery + HIPEC vs surgery + chemotherapy for the prophylaxis of peritoneal carcinomatosis and cytoreduction + HIPEC vs chemotherapy or other palliative options for the treatment of peritoneal carcinomatosis. RESULTS: Sixteen studies enrolling 1641 patients were included. Surgery + HIPEC significantly improved overall survival in both prophylactic (hazard ratio [HR], 0.56) and therapeutic (HR, 0.57) settings. When surgery + HIPEC was performed with prophylactic intent, the pooled 3-year mortality rate was 32%, whereas for the control group it was 55%. The overall and peritoneal recurrence rates were also reduced (risk ratio [RR], 0.59 and 0.40, respectively). No significant difference was found in morbidity between groups (RR, 0.92). CONCLUSION: Based on the current knowledge, HIPEC in AGC seems to be a safe and effective tool for prophylaxis and a promising resource for the treatment of peritoneal carcinomatosis. Regarding the treatment of peritoneal carcinomatosis, the scarcity of large-cohort studies and the heterogeneity of the techniques adopted prevented us from achieving a definitive recommendation.


Subject(s)
Cytoreduction Surgical Procedures , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms , Randomized Controlled Trials as Topic , Stomach Neoplasms , Humans , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Stomach Neoplasms/therapy , Stomach Neoplasms/pathology , Carcinoma/therapy , Carcinoma/secondary , Combined Modality Therapy
3.
Materials (Basel) ; 16(15)2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37569977

ABSTRACT

Nontoxic all-inorganic perovskites are among the most promising materials for the realization of optoelectronic devices. Here, we present an innovative way to deposit lead-free, totally inorganic Cs3Bi2I9 perovskite from vapor phase. Taking use of a magnetron sputtering system equipped with a radiofrequency working mode power supply and a single target containing the correct ratio of CsI and BiI3 salts, it was possible to deposit a Cs3Bi2I9 perovskitic film on silicon and soda-lime glass. The target composition was optimized to obtain a stoichiometric deposition, and the best compromise was found with a mix enriched with 20% w/w of CsI. Secondly, the effect of post-deposition thermal treatments (150 °C and 300 °C) and of the deposition on a preheat substrate (150 °C) were evaluated by analyzing the chemical composition, the morphology, the crystal structure, and the optical properties. The thermal treatment at 150 °C improved the uniformity of the perovskite film; the one at 300 °C damaged the perovskite deposited. Depositing on a preheated substrate at 150 °C, the obtained film showed a higher crystallinity. An additional thermal treatment at 150 °C on the film deposed on the preheated substrate showed that the crystallinity remains high, and the morphology becomes more uniform.

4.
Materials (Basel) ; 16(14)2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37512195

ABSTRACT

Physical Vapor Deposition (PVD) is a widely utilized process in various industrial applications, serving as a protective and hard coating. However, its presence in fields like fashion has only recently emerged, as electroplating processes had previously dominated this reality. The future looks toward the replacement of the most hazardous and toxic electrochemical processes, especially those involving Cr(VI) and cyanide galvanic baths, which have been restricted by the European Union. Unfortunately, a complete substitution with PVD coatings is not feasible. Currently, the combination of both techniques is employed to achieve new aesthetic features, including a broader color range and diverse textures, rendering de facto PVD of primary interest for the decorative field and the fashion industry. This review aims to outline the guidelines for decorative industries regarding PVD processes and emphasize the recent advancements, quality control procedures, and limitations.

5.
Front Surg ; 8: 624817, 2021.
Article in English | MEDLINE | ID: mdl-33816544

ABSTRACT

Introduction: Cholangiocarcinoma (CCA) is the second most common primary tumor of the liver, and the recurrence after hepatic resection (HR), the only curative therapy, is linked with a worse prognosis. Systemic chemotherapy (SC) and liver loco-regional treatments, like trans-arterial chemoembolization (TACE) or radio embolization (TARE), have been employed for the treatment of unresectable intrahepatic metastasis (IM) with benefit on overall survival (OS), but SC has a limited effect on peritoneal metastasis (PM). In the last years, novel treatments like electrochemotherapy (ECT) with bleomycine (BLM) for IM and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) for PM have been applied in small series but with encouraging results. We hereby describe the first synchronous application of ECT and CRS and HIPEC for the treatment of a patient with IM and PM from CCA. Case Description: A 47-year-old male patient with CCA underwent HR followed by adjuvant SC. After 14 months, for the occurrence of IM, the patient underwent a second HR and SC. Nonetheless, a new recurrence occurred and a third attempt of HR was proposed. Due to the intraoperative finding of unresectable IM with PM, no resective procedure was performed and the patient was referred to our center. CRS and HIPEC with cisplatin and mitomycin for PM and ECT with BLM on a bulky metastasis of the hepatic hilum were performed after 38 months from the first HR. The length of hospital stay was 19 days. At the computed tomography (CT) performed 11 days after treatment complete necrosis of the treated IM was detected. Results: CT scan after 3 and 6 months and magnetic resonance after 9 months were performed. Necrosis of the treated IM nor PM but progression of the residual liver lesions was observed. After 3 months, the patient received SC and underwent TACE after 8 months and TARE after 9 months for the residual liver metastases. At 14 months from CRS and HIPEC, the patient is alive, in good condition, and with stability of the disease. Conclusions: The association of ECT and CRS and HIPEC could be safe and effective for the treatment of unresectable recurrent intrahepatic CCA with PM.

6.
Carbohydr Polym ; 122: 408-16, 2015 May 20.
Article in English | MEDLINE | ID: mdl-25817685

ABSTRACT

An in situ forming hydrogel obtained by crosslinking of amino functionalized hyaluronic acid derivatives with divinylsulfone functionalized inulin (INU-DV) has been here designed and characterized. In particular two hyaluronic acid derivatives bearing respectively a pendant ethylenediamino (EDA) portion (HA-EDA) and both EDA and octadecyl pendant groups (HA-EDA-C18) were crosslinked through an azo-Michael reaction with INU-DV. Gelation time and consumption of DV portions have been evaluated on hydrogel obtained using HA-EDA and HA-EDA-C18 derivatives with a concentration of 3% w/v and a ratio 80/20 w/w respect to the crosslinker INU-DV. The presence of pendant C18 chains improves mechanical performances of hydrogels and decreases the susceptibility to hyaluronidase hydrolysis. Bovine chondrocytes, encapsulated during crosslinking, sufficiently survive and efficiently proliferate until 28 days of analysis.


Subject(s)
Cartilage/cytology , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Inulin/chemistry , Regeneration/physiology , Tissue Engineering , Animals , Cartilage/physiology , Cattle , Chondrocytes/cytology , Chondrocytes/physiology , Cross-Linking Reagents/chemistry , Microscopy, Electron, Scanning , Polymers/chemistry
7.
J Mater Chem B ; 2(21): 3243-3253, 2014 Jun 07.
Article in English | MEDLINE | ID: mdl-32261586

ABSTRACT

A two or one pot synthesis has been used for the reaction of hyaluronic acid (HA) with octadecylamine (C18) and hydrazine (Hy). In both cases, the chemical derivatization involved primary hydroxyl groups of hyaluronic acid and not its carboxyl groups, whose presence is important for receptor interaction. In this way, Hy-HA-C18 derivatives have been obtained with appropriate hydrophobic and hydrophilic character. Their ability to form homogeneous physical hydrogels has been evaluated as well as the possibility to obtain porous sponges through salt leaching technology. Sponges showing the highest porosity, potentially compatible with cell entrapment, have been characterized with regard to their physicochemical and biological properties. Swelling ability under simulated physiological conditions and stability in the absence or in the presence of hyaluronidase have been investigated. Bovine chondrocytes were viable in Hy-HA-C18 sponges as determined with MTS assay and were able to produce collagen and glycosaminoglycans, as assessed by using Masson's trichrome and Alcian blue, respectively. Finally, in vivo degradation of Hy-HA-C18 sponges has been confirmed after subcutaneous implantation in mice until 6 weeks.

8.
Mol Pharm ; 10(12): 4603-10, 2013 Dec 02.
Article in English | MEDLINE | ID: mdl-24206105

ABSTRACT

A graft copolymer of α-elastin with poly(lactic-co-glycolic) acid (PLGA) has been synthesized and successfully employed to produce nanoparticles. Exploiting the known biological activity of α-elastin to promote the maintenance of smooth muscle cells (SMCs) contractile phenotype and the antiproliferative effect of glucocorticoids, the aim of this research was to produce drug-loaded nanoparticles suitable for potential treatment of restenosis. In particular, nanoparticles of α-elastin-g-PLGA with a mean size of 200 nm have been produced and loaded with dexamethasone dipropionate (10% w/w), chosen as a model drug that inhibits proliferation of vascular SMCs. These nanoparticles are able to prolong the drug release and show a pronounced sensibility to elastase. Drug unloaded nanoparticles stimulate the differentiation of human umbilical artery smooth muscle cells (HUASMCs) toward the contractile phenotype as demonstrated by immunofluorescence, flow cytofluorimetric, and western blotting analyses. Finally, drug-loaded nanoparticles efficiently reduce viability of HUASMCs as evidenced by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.


Subject(s)
Coronary Restenosis/drug therapy , Dexamethasone/analogs & derivatives , Elastin/chemistry , Elastin/pharmacology , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Animals , Cattle , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Dexamethasone/chemistry , Dexamethasone/pharmacology , Drug Carriers/chemistry , Humans , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer
9.
Int J Pharm ; 457(1): 150-7, 2013 Nov 30.
Article in English | MEDLINE | ID: mdl-24060369

ABSTRACT

Atom transfer radical polymerization (ATRP) has been successfully employed to obtain a new derivative of hyaluronic acid (HA) able to change its solubility as a function of external pH and then to be potentially useful for intestinal release of bioactive molecules, included enzymes and proteins. In particular, a macroinitiator has been prepared by linking 2-bromo-2-methypropionic acid (BMP) to the amino groups of ethylenediamino derivative of tetrabutyl ammonium salt of HA (HA-TBA-EDA). This macroinititor, named HA-TBA-EDA-BMP has been used for the ATRP of sodium methacrylate (MANa) using a complex of Cu(I) and 2,2'-bipyridyl (Byp) as a catalyst. The resulting copolymer, named HA-EDA-BMP-MANa, has been characterized by (1)H NMR and size exclusion chromatography (SEC) analyses. A turbidimetric analysis has showed its pH sensitive behavior, being insoluble in simulated gastric fluid but soluble when pH increases more than 2.5. To confirm the ability of HA-EDA-BMP-MANa in protecting peptides or proteins from denaturation in acidic medium, α-chymotrypsin has been chosen as a model of protein molecule and its activity has been evaluated after entrapment into HA-EDA-BMP-MANa chains and treatment under simulated gastric conditions. Finally, cell compatibility has been evaluated by performing a MTS assay on murine dermal fibroblasts cultured with HA-EDA-BMP-MANa solutions.


Subject(s)
Chymotrypsin/administration & dosage , Hyaluronic Acid/analogs & derivatives , Hyaluronic Acid/chemistry , Administration, Oral , Animals , Cells, Cultured , Chromatography, Gel , Chymotrypsin/chemistry , Ethylenediamines/chemistry , Fibroblasts/drug effects , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Nephelometry and Turbidimetry , Polymerization , Quaternary Ammonium Compounds/chemistry , Rats , Rats, Wistar
10.
Int J Pharm ; 449(1-2): 84-94, 2013 Jun 05.
Article in English | MEDLINE | ID: mdl-23587968

ABSTRACT

Physical hydrogels have been obtained from hyaluronic acid derivatized with polylactic acid in the presence or in the absence of polyethylene glycol chains. They have been extemporarily loaded with antibacterial agents, such as vancomycin and tobramycin. These medicated hydrogels have been used to coat titanium disks (chosen as simple model of orthopedic prosthesis) and in vitro studies in simulated physiological fluid have been performed as a function of time and for different drug loading and polymer concentration values. Sterilization process performed on the hydrogels does not change their rheological behavior and release properties as well as the chemical structure of starting copolymers. A preliminary test has been performed by coating with the hydrogel a prosthesis that has been inserted in a seat of a lyophilized human femur, to confirm the ability of the hydrogel to adhere to the prosthesis surface also after its insertion in the implant seat. Cell compatibility of obtained hydrogels has been confirmed in vitro by using human dermal fibroblasts chosen as a model cell line. Obtained results suggest the potential use of these hydrogels in the orthopedic field, in particular for the production of antibacterial coatings of prostheses for implant in the human or animal body in the prevention and/or treatment of post surgical infections.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Hyaluronic Acid/chemistry , Lactic Acid/chemistry , Polymers/chemistry , Prosthesis-Related Infections/prevention & control , Cells, Cultured , Femur/surgery , Fibroblasts/metabolism , Humans , Hydrogels , Orthopedic Procedures/methods , Polyesters , Polyethylene Glycols/chemistry , Prosthesis Design , Rheology , Skin/cytology , Skin/metabolism , Sterilization , Titanium/chemistry , Tobramycin/administration & dosage , Vancomycin/administration & dosage
11.
Int J Pharm ; 433(1-2): 16-24, 2012 Aug 20.
Article in English | MEDLINE | ID: mdl-22575755

ABSTRACT

Polymeric microparticles encapsulating two model hydrophobic drugs, beclomethasone dipropionate (BDP) and flutamide (FLU) were prepared by using the high pressure homogenization-solvent evaporation method starting from a oil-in-water emulsion. For the preparation of polymeric microparticles a α,ß-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) graft copolymer with comb like structure was properly synthesized via grafting from atom transfer radical polymerization (ATRP) technique, by using two subsequent synthetic steps. In the first step a polymeric multifunctional macroinitiator was obtained by the conjugation of a proper number of 2-bromoisobutyryl bromide (BIB) residues to the PHEA side chains, obtaining the PHEA-BIB copolymer. PHEA-BIB copolymer was then used as macroinitiator for the polymerization via ATRP of the hydrophobic monomer such as butyl methacrylate (BMA) to obtain the α,ß-poly(N-2-hydroxyethyl)-D,L-aspartamide-co-(N-2-ethylen-isobutyrate)-graft-poly(butyl methacrylate) copolymer (PHEA-IB-p(BMA)). Spherical microparticles with 1-3 microns diameter were prepared. Microparticles loaded with BDP or FLU were also prepared. In vitro mucoadhesion and enzymatic degradation studies evidenced bioadhesive properties and biodegradability of prepared microparticles, while release studies showed a different release profiles for the two loaded drugs: BDP was totally released from nanoparticles until 24h in pulmonary mimicking conditions; differently a slower FLU release rate was observed in gastro-intestinal mimicking conditions. The in vitro cytotoxicity activity was assessed using 16HBE and Caco-2 cell lines. Results showed that exposure of both cell lines to BDP-loaded microparticles do not inhibited the cell growth; on the contrary FLU-loaded microparticles inhibited the cell growth, in particular of the Caco-2 cancer cell line, in a concentration- and time-dependent manner. Finally, uptake studies demonstrated that BDP-loaded microparticles and FLU-loaded microparticles effectively increased uptake of loaded drugs in a time-dependent manner, respectively on 16HBE and Caco-2 cell lines.


Subject(s)
Beclomethasone/administration & dosage , Flutamide/administration & dosage , Peptides/chemistry , Polymethacrylic Acids/chemistry , Adhesiveness , Androgen Antagonists/administration & dosage , Androgen Antagonists/chemistry , Androgen Antagonists/pharmacology , Beclomethasone/chemistry , Beclomethasone/pharmacology , Caco-2 Cells , Cell Line , Delayed-Action Preparations , Dose-Response Relationship, Drug , Drug Carriers/chemistry , Drug Delivery Systems , Emulsions , Flutamide/chemistry , Flutamide/pharmacology , Glucocorticoids/administration & dosage , Glucocorticoids/chemistry , Glucocorticoids/pharmacology , Humans , Hydrophobic and Hydrophilic Interactions , Microspheres , Nanoparticles , Particle Size , Solvents/chemistry , Time Factors
12.
Macromol Biosci ; 11(3): 445-54, 2011 Mar 10.
Article in English | MEDLINE | ID: mdl-21259438

ABSTRACT

A new PHEA-IB-PMANa(+) copolymer has been synthesized and its pH-induced self-assembly has been investigated in an aqueous medium. PHEA-IB-PMANa+ formed nanoparticles with diameters from 25 to 50 nm upon protonation of the carboxylic acid moieties dislocated along the grafted polymethacrylate sodium salt side chains. The physico-chemical characterization of the nanoparticles was performed using light scattering, zeta-potential measurements, SEM, and AFM. Doxorubicin-loaded nanoparticles were prepared and drug release profiles were evaluated under conditions mimicking physiological media. A biological characterization was carried out by testing the cytotoxicity on Caco-2 cells, and cellular uptake on mouse monocyte macrophage (J774 A.1) and Caco-2 cells.


Subject(s)
Doxorubicin/pharmacology , Drug Delivery Systems/methods , Nanoparticles/chemistry , Peptides/chemistry , Polymethacrylic Acids/chemistry , Animals , Caco-2 Cells , Cell Death/drug effects , Chemical Phenomena/drug effects , Chromatography, Gel , Humans , Light , Mice , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Microscopy, Fluorescence , Nanoparticles/ultrastructure , Peptides/chemical synthesis , Polymethacrylic Acids/chemical synthesis , Scattering, Radiation , Solutions
13.
Surg Endosc ; 25(2): 454-62, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20607562

ABSTRACT

BACKGROUND: There are few reports that show that laparoscopic rectal surgery for rectal cancer had similar oncological results based on short-term benefits. The purpose of this study was to analyze our institutional short- and long-term results in laparoscopic rectal surgery and to compare these results with that reported in the literature. METHODS: The records of 121 patients who underwent sphincter-saving procedure for rectal cancer were reviewed. The variables analyzed included possible factors causing morbidity, anastomotic leak, and recurrence rate in the laparoscopic and open techniques. Multivariable analyses were used to determine relationship between variables. Survival curves were determined by using the Kaplan-Meier method. RESULTS: Laparoscopic sphincter-saving total mesorectal excision or partial mesorectal excision was performed in 97 patients (group 1). Twenty-four patients had open procedure (group 2). The conversion rate from laparoscopic to open technique was 10.3% (n=10). The overall postoperative morbidity and anastomotic leak rates were 33.4% and 14.8%, respectively. There was no statistical difference in terms of postoperative morbidity (p=0.177) and anastomotic leak (p=0.216) between the two groups. Old age was an independent predictor for postoperative morbidity, and downstaging was an independent predictor for anastomotic leak with a sixfold increased risk. Complete downstaging to stage 0 showed a lower overall 5-year survival rate compared with non-downstaged stage I patients (79% vs. 100%). The overall local recurrence rate was 6%. There was one port site metastasis (0.8%). There were two (1.7%) postoperative deaths in group 1. The overall 5-year patient and disease-free survivals were 64% and 74%, respectively, and there was no difference between groups 1 and 2 (p=0.801). CONCLUSIONS: Laparoscopic sphincter-saving rectal resection for rectal cancer shows good long-term results. However, it has no advantage in terms of short-term benefits compared with the open procedure. Further studies are needed to validate the effect of downstaging on anastomotic leaks.


Subject(s)
Laparoscopy/methods , Laparotomy/methods , Neoplasm Recurrence, Local/pathology , Proctoscopy/methods , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Anal Canal , Anastomosis, Surgical , Cohort Studies , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Laparoscopy/adverse effects , Laparoscopy/mortality , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Proctoscopy/adverse effects , Prognosis , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Treatment Outcome
14.
Int J Pharm ; 396(1-2): 219-28, 2010 Aug 30.
Article in English | MEDLINE | ID: mdl-20600731

ABSTRACT

A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C(16)) moieties on polymer backbone, and the structure of obtained PAHy-PEG(2000)-C(16) copolymer have been characterized by 2D (1)H/(13)C NMR experiments. PAHy-PEG(2000)-C(16) copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D (1)H NMR NOESY experiments. The presence of cross-peaks for protons of C(16) and PAHy portions, indicated that the two domains are in close proximity forming micelle core. The critical aggregation concentration (CAC) values of PAHy-PEG(2000)-C(16) amphiphilic graft copolymer was determined in water by fluorescence technique, and it was demonstrated that PAHy-PEG(2000)-C(16) micelles are well suited to be micellar vehicle of highly hydrophobic molecules. Therefore, anticancer drug tamoxifen, used as a model hydrophobic molecule, was loaded into PAHy-PEG(2000)-C(16) micelles obtaining an increase of drug solubility of about 3000 times. Transmission electron microscopy (TEM) observations showed the spherical morphology of micelles formed by PAHy-PEG(2000)-C(16) copolymer with a mean diameter of about 30nm, as confirmed also by dynamic light scattering (DLS) studies. Finally, in vitro cell viability studies were carried out on human breast cancer cells (MCF-7) testing the pharmacological activity of tamoxifen-loaded PAHy-PEG(2000)-C(16) micelles, in comparison with free tamoxifen at different drug concentrations, demonstrating that tamoxifen-loaded PAHy-PEG(2000)-C(16) micelles exhibited a concentration-dependent cytotoxic activity.


Subject(s)
Antineoplastic Agents/chemistry , Drug Carriers , Micelles , Palmitic Acid/chemistry , Peptides/chemistry , Polyethylene Glycols/chemistry , Tamoxifen/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Chemistry, Pharmaceutical , Dose-Response Relationship, Drug , Drug Compounding , Female , Fluorescence , Humans , Hydrophobic and Hydrophilic Interactions , Light , Magnetic Resonance Spectroscopy , Microscopy, Electron, Transmission , Nanotechnology , Particle Size , Polymers , Scattering, Radiation , Tamoxifen/pharmacology , Technology, Pharmaceutical/methods
15.
Int J Pharm ; 390(2): 183-90, 2010 May 10.
Article in English | MEDLINE | ID: mdl-20153413

ABSTRACT

Poly[monomethylnona(ethylene glycol) 1-methylene-3-(4-methylphenyl)-1H-indene-2-carboxylate] (poly-1b) a new polymer based on a PEG-functionalized benzofulvene macromonomer have been investigated as hydrogel-based material for complexation and release of immunoglobulin (IgG) at physiological mimicking conditions. The polymer ability to complex human IgG has been studied by preparing copolymer/protein complexes obtained by spontaneous protein interactions onto polymer hydrogel aggregates, and the protein release rate has been evaluated at physiological conditions. SEM analysis was used to visualize the copolymer/IgG aggregates and its microstructured deposition. Moreover, rheological studies performed at 37 degrees C allowed determining hydrogel mechanical properties. On the basis of these information and NMR transverse relaxation measurements, the estimation of hydrogel mesh size distribution was possible. Finally, biological studies performed with poly-1b aqueous dispersions showed no cytotoxic effect on MCF-7 cell line, suggesting potential biocompatibility features for this polymer and making this new polymer a good potential candidate for the production of drug delivery systems.


Subject(s)
Drug Delivery Systems/methods , Hydrogels/chemistry , Immunoglobulin G/administration & dosage , Indenes/chemistry , Polyethylene Glycols/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Hydrogels/chemical synthesis , Immunoglobulin G/pharmacology , Indenes/chemical synthesis , Polyethylene Glycols/chemical synthesis , Polymers , Rheology , Surface Properties
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