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The synergy between nanostructured lipid carriers (NLC) and chemical penetration enhancers provides the basis for a promising strategy to effectively deliver drugs through the skin. In the present work, focus is given to the study of the interaction of limonene, ethanol, and Carbopol Ultrez 10NF, as the gelling agent, with a co-encapsulating NLC dispersion, containing both olanzapine and simvastatin. The analysis is based on rheological, mechanical, and physicochemical properties. The nanoparticle size ranged from 130 to 400 nm, depending on the system considered. The inclusion of carbopol resulted in a considerable increase in the NLC particle size, which was attributed to carbomer bridging nanoparticles, resulting in some particle aggregation. Rheological measurements indicated that the viscosity of the neat carbopol hydrogel was reduced by the enhancers and to a higher extent by the presence of NLC. A more apolar medium can be pointed out as a general explanation, while a polymer/nanoparticle hydrophobic interaction coupled with surfactant/polymer H-bonding provides the rationale for the NLC effect. The inclusion of enhancers and a carbomer largely contributed to the physicochemical stability of the NLC formulation, as revealed by the low transmission profiles and more negative zeta potential values. [ABSTRACT FROM AUTHOR]

Abstract: Colloidal and interfacial phenomena lie at the core of drug formulation, drug delivery, as well as drug binding and action at diseased sites, e.g., in cancer therapy. We review a class of liposome-based drug-delivery systems whose design and functional properties are intimately controlled by the stability of sub-micron structures, lipid-bilayer interfaces, and interfacially activated enzymes that can be exploited to target and deliver drugs. Moreover these drugs can themselves be special lipid molecules in the form of lipid prodrugs that both form the liposomal carrier as well as the substrate for endogenously upregulated lipases that turn the prodrugs into potent drugs precisely at the diseased site. [Copyright &y& Elsevier]

ABSTRACT Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic 'carrier' cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5 mm-long femur defect in a rat model occurs in under 3 weeks, through secretion of 100-fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2-3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1597-1604, 2013 [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of two silicone hydrogel (SiH) contact lenses, approved for continuous wear for one week, following photorefractive keratectomy (PRK). Methods: Forty seven myopic patients (94 eyes) undergone bilateral PRK were enrolled in this prospective, double-masked, comparative study. One eye of each patient was fitted with a Lotrafilcon B lens (Ciba Vision, Duluth, US; 30-day recommended replacement) whereas the fellow eye was fitted with an Asmofilcon A lens (Menicon, Nagoya, Japan; 14-day recommended replacement). Epithelial defect size was assessed using slit lamp biomicroscopy on the day of surgery and at days 1–4 post-operatively. Uncorrected and best-corrected visual acuity and retinal straylight (C-Quant, Oculus Optigerate, Germany) were evaluated pre-operatively and one month post-operatively. Results: Average epithelial defect size for Asmofilcon A and Lotrafilcon B was 25.5±11.0mm2 vs. 27.1±9.9mm2 at day 1 (p =0.007) and 6.3±7.0mm2 vs. 9.2±9.5mm2 at day 2 (p =0.012) post-operatively. Re-epithelialization at day 3 was completed in 87.2% of the eyes fitted with Asmofilcon A lenses, compared to 74.5% with Lotrafilcon B lenses (p =0.012). At the 3rd post-operative day 29.8% of re-epithelialized eyes showed irregular suture with Lotrafilcon B, compared to 12.8% eyes with Asmofilcon A lenses (p <0.001). Finally, no statistically significant differences were found post-operatively between the two lenses retinal straylight (p =0.98) and best-corrected visual acuity (p =0.68). Conclusions: SiH lenses can be used as an effective bandage after PRK due to the limited time requested for achieving complete corneal re-epithelialization. Faster and smoother epithelial healing is provided with Asmofilcon A over Lotrafilcon B lenses. [ABSTRACT FROM AUTHOR]

Purpose: to evaluate changes in tear metrics and ocular signs induced by six months of silicone-hydrogel contact lens wear and the difference in baseline characteristics between those who successfully continued in contact lens wear compared to those that did not. Methods: Non-invasive Keratograph, Tearscope and fluorescein tear break-up times (TBUTs), tear meniscus height, bulbar and limbal hyperaemia, lid-parallel conjunctival folds (LIPCOF), phenol red thread, fluorescein and lissamine-green staining, and lid wiper epitheliopathy were measured on 60 new contact lens wearers fitted with monthly silicone-hydrogels (average age 36±14 years, 40 females). Symptoms were evaluated by the Ocular Surface Disease Index (OSDI). After six months full time contact lens wear the above metrics were re-measured on those patients still in contact lens wear (n =33). The initial measurements were also compared between the group still wearing lenses after six months and those who had ceased lens wear (n =27). Results: There were significant changes in tear meniscus height (p =0.031), bulbar hyperaemia (p =0.011), fluorescein TBUT (p =0.027), corneal (p =0.007) and conjunctival (p =0.009) staining, LIPCOF (p =0.011) and lid wiper epitheliopathy (p =0.002) after six months of silicone-hydrogel wear. Successful wearers had a higher non-invasive (17.0±8.2s vs 12.0±5.6s; p =0.001) and fluorescein (10.7±6.4s vs 7.5±4.7s; p =0.001) TBUT than drop-outs, although OSDI (cut-off 4.2) was also a strong predictor of success. Conclusion: Silicone-hydrogel lenses induced significant changes in the tear film and ocular surface as well as lid margin staining. Wettability of the ocular surface is the main factor affecting contact lens drop-out. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of increasing experience on hydrogel dimensions, rectal dose, and acute toxicity, and to discuss important technical issues gained from this experience. Methods: Sixty-four consecutive patients with prostate cancer were included in this analysis (G1/G2 corresponding to first/second 32 patients) after injection of 10 mL spacer gel. All patients were treated with a 5-field intensity-modulated radiotherapy technique to 76-78 Gy. Treatment toxicity was evaluated with a validated quality of life questionnaire (expanded prostate cancer index composite) before and after radiotherapy. Results: Rectum volume could be entirely excluded from the planning target volume in 31% in G1 vs 56% in G2 (P = .04). Increasing symmetry was detected comparing the first 15 patients to the subsequent rest, with mean differences between right and left of 0.6 cm vs 0.3 cm at the midgland (P = .03). Mean distance between prostate and anterior rectal wall increased from 0.8 cm/1.1 cm/0.8 cm (G1) at the base/middle/apex to 1.3 cm/1.5 cm/1.2 cm (G2), respectively, so that the dose to the rectum decreased significantly (6% vs 2% of the volume inside the 70 Gy isodose; P <.01). Bowel function and bother score changes were smaller comparing baseline with last day of radiotherapy levels (mean 16/18 in G1 vs 9/12 in G2). Conclusion: A learning curve could be demonstrated in our patient population, respecting improved and more symmetrical spacer placement, improved treatment planning, and less treatment-related acute toxicity. Several important technical aspects need to be considered. [Copyright &y& Elsevier]

Abstract: In the 40 years since Elsdale and Bard's analysis of fibroblast culture in collagen gels we have moved far beyond the concept that such 3D fibril network systems are better models than monolayer cultures. This review analyses key aspects of that progression of models, against a background of what exactly each model system tries to mimic. This story tracks our increasing understanding of fibroblast responses to soft collagen gels, in particularly their cytoskeletal contraction, migration and integrin attachment. The focus on fibroblast mechano-function has generated models designed to directly measure the overall force generated by fibroblast populations, their reaction to external loads and the role of the matrix structure. Key steps along this evolution of 3D collagen models have been designed to mimic normal skin, wound repair, tissue morphogenesis and remodelling, growth and contracture during scarring/fibrosis. As new models are developed to understand cell-mechanical function in connective tissues the collagen material has become progressively more important, now being engineered to mimic more complex aspects of native extracellular matrix structure. These have included collagen fibril density, alignment and hierarchical structure, controlling material stiffness and anisotropy. But of these, tissue-like collagen density is key in that it contributes to control of the others. It is concluded that across this 40 year window major progress has been made towards establishing a family of 3D experimental collagen tissue-models, suitable to investigate normal and pathological fibroblast mechano-functions. [Copyright &y& Elsevier]

Abstract: Background: Colloids are widely used for fluid resuscitation in patients with sepsis. But the optimal type of fluid remains unclear. Objective: Our aim was to assess the effects on mortality and safety of different colloid solutions in patients with sepsis requiring volume replacement by examining direct comparisons of colloid solutions. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, China Biological Medicine Database, VIP Chinese Journals Database, and CNKI China National Knowledge Infrastructure Whole Article Database. Randomized clinical trials comparing different colloids in septic patients needing fluid resuscitation were selected. Results: Seventeen randomized clinical trials with a total 1281 participants met the inclusion criteria. Mortality was obtained in all trials. For intervention of albumin vs. hydroxyethyl starch solution (HES), the relative risk (RR) of death was 0.98 (95% confidence interval [CI] 0.74−1.30). For intervention of albumin vs. gelatin, the RR of death was 2.4 (95% CI 0.31−18.35). For intervention of gelatin vs. HES, the RR of death was 1.02 (95% CI 0.79−1.32). For the intervention of HES vs. dextran, the RR of death was 1.38 (95% CI 0.28−6.78). For the intervention of gelatin vs. dextran, RR of death was not estimable. For albumin vs. dextran, no trial was included. Four trials of intervention of albumin vs. HES recorded the change of severity score. Conclusions: There is no evidence that one colloid solution is more effective and safer than another for fluid resuscitation in sepsis. The severity score is improved in HES, but the confidence intervals are wide. [Copyright &y& Elsevier]

Abstract: Highly porous nanocellulose aerogels prepared by freeze-drying from various nanofibrillar cellulose (NFC) hydrogels are introduced as nanoparticle reservoirs for oral drug delivery systems. Here we show that beclomethasone dipropionate (BDP) nanoparticles coated with amphiphilic hydrophobin proteins can be well integrated into the NFC aerogels. NFCs from four different origins are introduced and compared to microcrystalline cellulose (MCC). The nanocellulose aerogel scaffolds made from red pepper (RC) and MCC release the drug immediately, while bacterial cellulose (BC), quince seed (QC) and TEMPO-oxidized birch cellulose-based (TC) aerogels show sustained drug release. Since the release of the drug is controlled by the structure and interactions between the nanoparticles and the cellulose matrix, modulation of the matrix formers enable a control of the drug release rate. These nanocomposite structures can be very useful in many pharmaceutical nanoparticle applications and open up new possibilities as carriers for controlled drug delivery. [Copyright &y& Elsevier]

Highlights: [•] The work is development of delivery system using biocompatible porcine articular cartilage (PCP). [•] BSA-loaded PCP suspension become gel upon s.c. injection into rats. [•] PCP hydrogels exhibit sustained release of BSA over extended experimental periods. [•] PCP hydrogel may provide numerous benefits as a minimally invasive therapeutics depot. [ABSTRACT FROM AUTHOR]

Abstract: In this study, transdermal gel formulations for tolterodine were developed to investigate the effects of gel matrix and chemical enhancers on drug skin permeation from tolterodine hydrogels. In vitro permeation studies of tolterodine through excised mouse skin were carried out using Franz-type diffusion cells. In the optimum gel formulation, Carbopol 940 was selected as the gel matrix. Compared to gels without enhancer, tolterodine hydrogels with N-methyl pyrrolidone (NMP) showed significant enhancing effect on transdermal permeation of tolterodine (p <0.05). The results of in vitro percutaneous delivery experiment showed that the relationship of the steady accumulative percutaneous amount (Q, μgcm−2) of tolterodine hydrogels and time was Q 4–12h =770.19t 1/2 −966.99. Tolterodine permeated at the steady-state speed of 770.19μgcm−2 h−1 and its release coincided with Higuchi Equation. The pharmacokinetic properties of the optimized tolterodine formulation were studied in rabbits. The absolute bioavailability of tolterodine was 11.47%. Since the absence of hepatic first-pass metabolism, only a single active compound-tolterodine was detected in the plasma. A skin irritation study was also carried out on rabbits, and the results showed tolterodine hydrogels had no skin irritation. In the pharmacodynamic study, the significant effects of tolterodine hydrogels on the inhibition of pilocarpine-induced rat urinary bladder contraction were last to 12h, indicating that tolterodine hydrogels could produce prolonged pharmacological responses. In conclusion, tolterodine hydrogels were formulated successfully using Carbopol 940 and NMP and these results helped in finding the optimum formulation for percutaneous drug release. It is quite evident that tolterodine hydrogels may offer a possibility to avoid the first-pass effect, resulting in a single active compound of tolterodine in plasma, which may profit on the patient under the dose control and the reduction of potential adverse effect from two active compounds in the body. [Copyright &y& Elsevier]

The current study involved investigation of the effect of storage temperature and moisture on the performance of poly(lactide-co-glycolide) (PLGA) microsphere/poly(vinyl-alcohol) (PVA) hydrogel composites. Physical aging occurred in composites stored at 25°C due to structural relaxation. The glass transition temperature (Tg) and enthalpy of relaxation of the composites increased leading to a slower cumulative % release. The Tg of composites incubated at 40°C, 75% RH decreased significantly due to the plasticization effect of absorbed water, whereas no change was observed in the Tg of microspheres alone; indicating that the hydrogel component enhanced water absorption. PLGA degradation occurred leading to significantly faster dexamethasone release following incubation at 40°C, 75% RH for 1 month. No significant change was observed in the in vitro release profiles of composites after 6 months storage at 25°C, 60% RH, however, release was accelerated following 12 months storage. Accordingly, exposure of the composites to ambient temperature/moisture during storage, shipping or handling may cause physical aging, plasticization, and degradation and hence, their performance may be affected. The extent to which the performance of the composite is affected by storage temperature and moisture is a net effect of physical aging and moisture induced plasticization/hydrolytic degradation. [ABSTRACT FROM AUTHOR]

Abstract: The effect of different preparation parameters were analyzed with respect to the rheological and pharmaceutical characteristics of hydrogel blend patches, as transdermal delivery formulation. Mixtures of pectin and gelatin were employed for the production of patches, with adjustable properties, following a two-step gelation procedure. The first gelation, a thermal one, is trigged by the presence of gelatin, whereas, the second gelation, an ionic one, is due to the formation of the typical egg box structure of pectin. In particular, the patch structural properties were assessed by oscillation stress sweep measurements which provided information concerning their viscolelastic properties. In addition, different modalities for drug loading were analyzed with respect to drug homogeneous distribution; testosterone was employed as model drug for transdermal administration. Finally, the performances of the produced transdermal patches were studied, in term of reproducibility and reliability, by determination of in vitro drug release profiles. [Copyright &y& Elsevier]

Abstract: The presented research was oriented towards the preparation of dry biodegradable alginate aerogels with multi-membranes using a multi-step sol–gel process with potential applications as carriers during oral drug delivery. First alginate spherical hydrogels were formed in CaCl2 or BaCl2 solutions by ionic cross-linking. These cores were further immersed into alginate sodium solution, filtered through a sieve, and dropped into the salt solution again. Multi-membrane hydrogels were obtained by repeating the above process. They were further converted into aerogels by supercritical drying. The effect of the number of membranes was investigated regarding the loading and release of the model drugs nicotinic acid and theophylline. Moreover, the efficiencies of Ba2+ and Ca2+ metal ions for forming tridimensional networks that retain and extend drug release were also investigated. Nicotinic acid release was prolonged by adding membranes around the core and using Ca2+ for cross-linking. However, retarded theophylline release was only obtained by using Ba2+ for cross-linking. Namely, by increasing the number of membranes and BaCl2 concentration drug release became linear versus time in all studied cases. In the case of nicotinic acid loading increased by adding membranes around the core, however, for theophylline the opposite results were obtained due to the different nature of the model drugs. [Copyright &y& Elsevier]

Hydrogels are widely used as scaffolds in tissue engineering because they can provide excellent environments for bioactive components including growth factors and cells. We reported in this study on a physical hydrogel formed by a specific protein-peptide interaction, which could be used for the three dimensional (3D) cell culture of murine mesenchymal stem cells (mMSC). The mMSC kept dividing during the 7-day culture period and the metabolic-active cell number at day 7 was 359% more than that at day 1. This kind of physical hydrogel could be converted to a homogeneous solution by firstly adding an equal volume of culture medium and then pipeting for several times. Therefore, mMSC post culture could be easily separated from cell-gel constructs. We believed that the protein-based hydrogel system in this study could be developed into a promising scaffold for in vitro expansion of stem cells and cell therapy. This work would be in the general interests of researchers in the fields of biomaterials and supramolecular chemistry. [ABSTRACT FROM AUTHOR]

In order to investigate the tribological behavior of medical devices in contact with tissue, friction tests for four kinds of medical metallic alloys (316L stainless steel, CoCr, NiTi and TiMoSn) on soft tissue-mimicking poly(vinyl alcohol) hydrogel (PVA-H) biomodel were carried out at low normal load. XPS analysis and wettability tests for them were prepared to understand the difference in friction. According to the surface oxide compositions, these alloys can be divided into two groups: 'Fe/Cr-oxide-surface alloys' for 316L and CoCr, and 'Ti-oxide-surface alloys' for NiTi and TiMoSn. From the wettability test, Fe/Cr-oxide-surface alloys show lower polar components of surface free energy than Ti-oxide-surface alloys. Fe/Cr-oxide-surface alloys show higher friction coefficients in the elastic friction domain than those of Ti-oxide-surface alloys, while there was no significant difference in the hydrodynamic lubrication. Since elastic friction is governed by the adsorption of hydrogel polymer on counterbody, the surface characteristic of alloys plays an important role in friction. A tentative explanation for this tendency is expressed by linking two different theories describing the adsorption force of hydrogel and wettability of countermaterial. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. Methods and Materials: Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. Results: Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. Conclusions: Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results. [Copyright &y& Elsevier]

Abstract: Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS. [Copyright &y& Elsevier]

Purpose: Hydrogel composites of oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles (GMs) were investigated as carriers of bone morphogenetic protein-2 (BMP-2) for bone tissue engineering applications. Methods: Hydrogel composites with different physical characteristics were prepared by changing the amount and type (acidic vs. basic) of gelatin incorporated in the OPF bulk phase. Composites with differing physical properties (degradation, swelling, and mechanical properties) and differing BMP-2 loading phase were investigated to determine the effect of these factors on BMP-2 release profiles over 28 days. Results: Overall, higher gelatin amount increased the degradation and swelling of composites, and acidic GMs further increased the degradation and swelling and reduced the compressive modulus of the composites. The most significant factor affecting the release of BMP-2 from composites was the loading phase of the growth factor: GM loading reduced the burst release, increased BMP-2 release during the later phases of the experiment, and increased the cumulative release in faster degrading samples. Conclusions: The results indicate that the physical properties and the BMP-2 release kinetics of hydrogel composites can be controlled by adjusting multiple parameters at the time of the hydrogel composite fabrication. [ABSTRACT FROM AUTHOR]

Highlights: [•] A biodegradable and non-toxic polysaccharides cross-linked hydrogels was developed. [•] Avastin loaded hydrogel for ocular drug delivery. [•] Avastin was sustained release from hydrogel with well structure stability. [Copyright &y& Elsevier]

This review generalizes scientific information on factors that determine the efficacy of transdermal drug delivery, including the barrier functions of skin, the properties of drugs and enhancers of skin permeability, and the type of a transdermal therapeutic system, i.e., plaster. Colloidochemical aspects of transdermal drug delivery are considered in relation to the amphiphilic structure of drugs and action mechanisms of enhancers, among which nonionic surfactants prevail. Advantages of microreservoir-type transdermal therapeutic systems are shown, information on which is very scarce; the prospects of their development on the basis of oil-in-water and water-in-oil emulsions containing nonionic surfactants and polymer adhesives are outlined. [ABSTRACT FROM AUTHOR]

Polyacrylamide is a widely used material in cell mechanobiology research. Here, we validate and optimize a method to activate polyacrylamide substrates for protein patterning, resulting in a system with precise and independent control over the geometric and mechanical factors that cells perceive. Acrylic acid incorporated into the hydrogel provides functional sites for activation with N-hydroxysuccinimide, which in turn forms covalent bonds with proteins printed in microscale patterns. To validate and optimize substrate fabrication, we demonstrate that acrylic acid incorporates into the polymer, that is has no effect on Young's modulus at up to 0.4 wt%, and that increasing concentrations of acrylic acid result in substrates with increasing amounts of protein bound to them. Finally, we demonstrate that cells attach and spread to substrates with protein patterned with electrohydrodynamic jet (e-jet) printing. The method represents an improvement over the most-widely used method to chemically activate polyacrylamide with sulfo-SANPAH. With further refinement, truly independent control over ligand density and stiffness is possible. These substrates are powerful platforms for exploring the interacting influence of substrate stiffness and ligand density on cell behavior. [ABSTRACT FROM AUTHOR]

Drug delivery mediated by hydrogel has shown great promise in controlled drug release field. We report here the development of a hydroxybutyl chitosan (HBC) thermo-sensitive gel to deliver doxorubicine hydrochloride (DOX·HCl) for cancer treatment. Concentrated HBC aqueous solution could transform into hydrogel within 30 s after injection under physiological temperature in non-chemical fashion. The properties of the HBC gels including chemical structure, surface morphology, and rheologic properties were studied. Gelation temperature and gelation time of HBC could be adjusted by HBC concentrations. The gel erosion rate in vivo was faster than solubilization rate in vitro. The mild inflammatory response caused by implantation of the hydrogel was acceptable. The DOX·HCl (1 mg/ml) loaded HBC gels displayed slow release rates that were independent of the HBC concentration, and significantly reduced viability of 4T-1 cells compared with the HBC gels after 1 day incubation. These results indicate that thermo-sensitive HBC hydrogels have promising potential as an injectable drug carrier for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Softhydrogel particles with tunable mechanical properties arepromising for next-generation therapeutic applications. This is dueto the increasingly proven role that physicochemical properties playin particulate-based delivery vectors, both in vitroand in vivo. The ability to understand and quantifythe mechanical properties of such systems is therefore essential tooptimize function and performance. We report control over the mechanicalproperties of poly(methacrylic acid) (PMA) hydrogel particles basedon a mesoporous silica templating method. The mechanical propertiesof the obtained particles can be finely tuned through variation ofthe cross-linker concentration, which is hereby quantified using across-linking polymer with a fluorescent tag. We demonstrate thatthe mechanical properties of the particles can be elucidated usingan atomic force microscopy (AFM) force spectroscopy method, whichadditionally allows for the study of hydrogel material propertiesat the nanoscale through high-resolution force mapping. Young’smodulus and stiffness of the particles were tuned between 0.04 and2.53 MPa and between 1.6 and 28.4 mN m–1, respectively,through control over the cross-linker concentration. The relationshipbetween the concentration of the cross-linker added and the amountof adsorbed polymer was observed to follow a Langmuir isotherm, andthis relationship was found to correlate linearly with the particlemechanical properties. [ABSTRACT FROM AUTHOR]

While soft hydrogel nano- and microstructureshold great potentialfor therapeutic treatments and in vivo applications, their nanomechanicalcharacterization remains a challenge. In this paper, soft, single-component,supported hydrogel films were fabricated using pendant-thiol-modifiedpoly(methacrylic acid) (PMASH). The influence of hydrogelarchitecture on deformation properties was studied by fabricatingfilms on particle supports and producing free-standing capsules. Theinfluence of the degree of thiol-based cross-linking on the mechanicalproperties of the soft hydrogel systems (core–shell and capsules)was studied using a colloidal-probe (CP) AFM technique. It was foundthat film mechanical properties, stability, and capsule swelling couldbe finely tuned by controlling the extent of poly(methacrylic acid)thiol modification. Furthermore, switching the pH from 7.4 to 4.0led to film densification due to increased hydrogen bonding. Hydrogelcapsule systems were found to have stiffness values ranging from 0.9to 16.9 mN m-1over a thiol modification range of5 to 20 mol %. These values are significantly greater than those forpreviously reported PMASHplanar films of 0.7–5.7mN m–1over the same thiol modification range (Best et al., Soft Matter2013, 9, 4580–4584). Films on particlesubstrates had comparable mechanical properties to planar films, demonstratingthat while substrate geometry has a negligible effect, membrane andtension effects may play an important role in capsule force resistance.Further, when transitioning from solid-supported films to free-standingcapsules, simple predictions of shell stiffness based on modulus changesfound for supported films are not valid. Rather, additional effectslike diameter increases (geometrical changes) as well as tension buildupneed to be taken into account. These results are important for researchrelated to the characterization of soft hydrogel materials and controlover their mechanical properties. [ABSTRACT FROM AUTHOR]

Highlights: [•] Peptide hydrogel. [•] Biocompatible trigger to form hydrogels. [•] 3D cell culture. [Copyright &y& Elsevier]

Abstract: A precise spatial multicellular polymer hydrogel matrix was prepared by successive assembly of cell-laden hydrogel layers alternated by hydrogel layers without cells based on the spontaneous hydrogel formation between 2 aqueous polymer solutions. The polymers used were a water-soluble 2-methacryloyloxyethyl phosphorylcholine polymer bearing phenylboronic acid groups (PMBV) and poly(vinyl alcohol) (PVA). Each cell-laden layer was deposited as a cell-laden PMBV solution on a PMBV/PVA precursor film. PMBV/PVA multilayer hydrogel was stacked on the top of a cell-laden layer by sequential coating with spinning of the PMBV and PVA solutions. This process allowed the formation of the PMBV/PVA multilayer hydrogel with finely controlled thickness. Finally, we succeeded in cell patterning by using a multilayer hydrogel matrix, forming a sandwich of 2 cell-laden layers separated by a PMBV/PVA multilayer hydrogel. The cells remained alive during the spinning process and maintained their metabolism for at least 24h. This precise spatial multicellular PMBV/PVA hydrogel can be used to examine interactions between many different cells and construct customized microenvironments for multicellular co-cultures. [Copyright &y& Elsevier]

Highlights: [•] Ultrasonication is applied for preparation of nano-sized indomethacin particles. [•] Encapsulation with polysaccharides is used to protect particles from aggregation. [•] Controlled release of indomethacin is realized by increasing pH in the solution. [Copyright &y& Elsevier]

Highlights: [•] PMMA NPs were prepared by emulsion free radical polymerization. [•] NPs were loaded in chemical cross-linked hydrogels to guarantee suitable drug release profiles. [•] Different sized NPs were loaded in different entangled hydrogels to create a tunable material library. [•] Mathematical model provides a complete understanding of material library behavior. [•] In vivo studies were performed to confirm in vitro release kinetics. [Copyright &y& Elsevier]

A thermosensitive micelles-hydrogel hybrid system based on Poloxamer 407 (P407) was prepared to resolve the fast erosion and low loading capability of lipophilic drug of P407 gels for local chemotherapy. Different amounts of glutaraldehyde (GA) were applied to generate cross-linked networks with carboxymethyl chitosan (CMCS) interpenetrated in P407 gels, in which paclitaxel (PTX)-loaded N-octyl- O-sulfate chitosan micelles (PTX-M) were dispersed uniformly. The in vitro characteristics of CMCS-modified P407 gels (PTX-M-MG) were performed by examining the viscosity, swelling ratio, mechanical property, and drug release, while the in vivo evaluation included tissue distribution and anticancer efficacy through intratumoral administration in hepatoma solidity cell (Heps) tumor-bearing mice. The results showed that PTX-M-MG containing 0.05% (w/v) GA possessed lower viscosity, higher swelling ratio, stronger mechanical property, and longer term drug release, in which the loading efficiency of PTX was enlarged by the introduction of PTX-M. Moreover, PTX-M-MG revealed a prolonged retention at tumor sites, lasting for 20 days, and a superior tumor inhibition rate (64.27%) with reduced toxicity compared with Taxol®, PTX-M, and PTX-M loaded unmodified P407 gels (PTX-M-P407). It can be concluded that PTX-M-MG is a promising local delivery system for hydrophobic drug in cancer therapy, providing both improved efficacy and relieved side effects. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2707-2717, 2013 [ABSTRACT FROM AUTHOR]

Endogen polyamines are known to be molecules of high biological value. Herein, a new generation of physical hydrogels was developed through the mild ionotropic gelantion technique, using the endogen polyamine spermidine as a physical cross-linker. The main negatively charged polymer of the hydrogel is the natural polysaccharide gellan gum. Optionally, interesting endogen molecules, such as chondroitin sulfate and albumin, can be included as part of the formulation. These new hydrogels were characterized and the influence of the different components on their final properties was carefully analyzed, ultimately demonstrating the possibility to modulate these properties as well as the system's versatility in terms of composition. On the contrary, in vitro cell studies showed the absence of cytotoxicity of these hydrogels. Finally, the in vitro-release profiles obtained for different model molecules evidenced the potential of these systems as novel drug delivery platforms. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2632-2643, 2013 [ABSTRACT FROM AUTHOR]

Abstract: The creation of branched vascular systems has attracted significant attention from both scientific and clinical areas. However, it is still a formidable challenge to build a three-dimensional (3-D) branched vascular system mimicking the native vascular systems with the traditional or existing fabrication methods. Here we demonstrate rapid manufacturing of a hybrid hierarchical polyurethane-cell/Hydrogel construct by a double-nozzle low-temperature deposition system. Based on this approach, a 3-D vascular template with both synthetic scaffold polymer and cell/hydrogel systems was constructed. The synthetic PU was used as an external scaffold material to provide mechanical support, while the gelatin/alginate/fibrinogen hydrogel was used as an internal scaffold material for adipose-derived stem cell (ADSC) accommodation. After the fabrication stages, the coherent 3-D composite construct was thawed at room temperature, crosslinked/polymerized with aqueous solutions, cultured in vitro under static or dynamic conditions, and embedded in vivo with stable architectures and excellent biocompatibilities. This technology will enable rapid manufacture of complex branched vascular templates for a wide array of scientific and clinical applications. [Copyright &y& Elsevier]

Abstract: Peripheral nerve injuries requiring surgery can be repaired by autograft, the clinical “gold standard”, allograft, or nerve conduits. Most published clinical studies show the effectiveness of nerve conduits in small size defects in sensory nerves. Many preclinical studies suggest that peripheral nerve regeneration through conduits can be enhanced and repair lengths increased with the use of a biomaterial filler in the conduit lumen. We have previously shown that a luminal hydrogel filler derived from human hair keratin (HHK) can improve electrophysiological and histological outcomes in mouse, rabbit, and non-human primate nerve injury models, but insight into potential mechanisms has been lacking. Based on the premise that a keratin biomaterial (KOS) hydrogel provides an instantaneous structural matrix within the lumen, the current study compares the cellular behavior elicited by KOS hydrogel to Matrigel (MAT) and saline (SAL) conduit fillers in a 1 cm rat sciatic nerve injury model at early stages of regeneration. While there was little difference in initial cellular influx, the KOS group showed earlier migration of dedifferentiated Schwann cells (SC) from the proximal nerve end compared to the other groups. The KOS group also showed faster SC dedifferentiation and myelin debris clearance, and decreased macrophage infiltration during Wallerian degeneration of the distal nerve tissue. [Copyright &y& Elsevier]

The corium is decreased to about half of its thickness in skin defects and wrinkles due to gravity and environment. In this study, dexamethasone/poly(d,l-lactic acid) (Mn = 160,000) microspheres were incorporated into poly(ethylene glycol)–poly(ɛ-caprolactone)–poly(ethylene glycol) (Mn = 3300) hydrogel to prepare an injectable hydrogel composite. The composite was designed to increase the thickness of the corium. Dexamethasone/poly(d,l-lactic acid) microspheres were prepared by oil-in-water emulsion/solvent evaporation technique. The properties of microspheres were investigated by size distribution measurement, scanning electron microscope and x-ray diffraction. Drug loading, encapsulation efficiency, and drug delivery behavior of microspheres were also studied in detail. Cell adhesion of microspheres was investigated by NIH3T3 cell in vitro. The properties of hydrogel composite were investigated by scanning electron microscope, rheological measurements and methyl thiazolyl tetrazolium assay. Drug release from composite was determined by HPLC-UV analysis. These results suggested that poly(d,l-lactic acid) microspheres encapsulating dexamethasone embedded in poly(ethylene glycol)–poly(ɛ-caprolactone)–poly(ethylene glycol) hydrogel might have prospective application in orthopedic tissue engineering field. [ABSTRACT FROM AUTHOR]

In present study, the chitosan/starch/β-glycerol phosphate hydrogel was investigated as an effective carrier for chondrocytes and delivery of transforming growth factor-β1. In vitro study indicated that transforming growth factor-β1 was released sustainably for 14 days with its biological activity to stimulate chondrocyte functions, as indicated by the strong expression of type II collagen protein. Subcutaneous implantation to rats revealed the strong expressions of type II collagen and aggrecan messenger ribonucleic acids, and also type II collagen protein was observed in the hydrogel in combination with transforming growth factor-β1 within 2 weeks. Our collective results showed the potential of chitosan/starch/β-glycerol phosphate hydrogel for effective delivery of chondrocytes and transforming growth factor-β1, and preserve chondrocytes’ phenotype and functions in vitro. [ABSTRACT FROM AUTHOR]

Highlights: [•] Phenolic compounds were identified in honeysuckle, white-bryony and black-bryony. [•] Honeysuckle showed the highest concentrations of phenolic compounds. [•] The antioxidant activity was similar among the three assayed species. [•] The prepared hydrosoluble gels kept the antioxidant activity. [•] The studied species can be used in formulations for topical use. [ABSTRACT FROM AUTHOR]

Abstract: Sentinel lymph nodes (SLNs) are the first lymph nodes which cancer cells reach after traveling through lymphatic vessels from the primary tumor. Evaluating the nodal status is crucial in accurate staging of human cancers and accordingly determines prognosis and the most appropriate treatment. The commonly used methods for SLN identification in clinics are based on employment of a colloid of radionuclide or injection of a small dye. Although these methods have certainly contributed to improve surgical practice, new imaging materials are still required to overcome drawbacks of the techniques such as inconvenience of handling radioactive materials and short retention time of small dyes in SLNs. Here, we prepare a fluorescence-labeled DNA tetrahedron and perform SLN imaging by using the DNA nanoconstruct. With a successful identification of SLNs by the DNA nanoconstruct, we suggest that DNA tetrahedron hold great promises for clinical applications. [Copyright &y& Elsevier]

Highlights: [•] We describe the microbial characterisation of hydrogel-forming microneedles. [•] Microneedle materials did not support microbial growth. [•] No microorganisms crossed the epidermal skin when microneedles were used. [•] With hypodermic needles, Candida albicans and Staphylococcus epidermidis crossed epidermal skin. [•] Human volunteer studies confirmed that skin or systemic infection is unlikely. [Copyright &y& Elsevier]

Trauma is a leading cause of death worldwide and traumatic brain injury is one of the commonest injuries associated with it. The need for urgent resuscitation is warranted for prevention of secondary insult to brain. However, the choice of fluid in such cases is still a matter of conflict. The literature does not provide enough data pertaining to role of colloids in head injury patients. In this article, we have tried to explore the present role of colloid resuscitation in patient with head injury. [ABSTRACT FROM AUTHOR]

Abstract: Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine. [Copyright &y& Elsevier]

Abstract: Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000g/m2/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing. [Copyright &y& Elsevier]

Background Postoperative adhesion formation is a common consequence of abdominal surgery, and constitutes a major source of morbidity and mortality. This study evaluated an ultrapure alginate-based antiadhesive barrier gel. Methods Experiments were performed in a rat model with caecal abrasion and peritoneal side wall excision. The primary endpoint was the incidence of adhesions at 14 days after surgery. In experiment 1 (24 rats), animals treated with alginate gel were compared with controls that had no antiadhesive barrier. In experiment 2 (42 rats), alginate gel was compared with sodium hyaluronate carboxymethyl cellulose ( HA/ CMC) membrane and with no antiadhesive barrier. To check for any remote action of the gel, in experiment 3 (45 rats) application of alginate gel to the ipsilateral versus contralateral side of injury was compared with no antiadhesive barrier. Results In experiment 1, ultrapure alginate gel reduced the incidence of adhesions from eight of 12 in control animals to one in 12 ( P = 0·009). Tissue healing assessed by histology was similar in both groups. In experiment 2, ultrapure alginate gel and HA/ CMC membrane showed similar antiadhesive effectiveness, reducing the incidence of adhesions from ten of 14 rats in the control group to three of 14 ( P = 0·021) and two of 14 ( P = 0·006) respectively. In experiment 3, ultrapure alginate gel reduced the incidence of adhesions at the site of direct application (1 of 15) compared with controls (13 of 15; P = 0·001), but not if applied remotely (9 of 15; P = 0·214). Conclusion Ultrapure alginate gel decreased the incidence of postoperative adhesion formation in this rat model. [ABSTRACT FROM AUTHOR]

This investigation describes the synthesis and in vitro evaluation of cationic hydrogel sub-microparticles based on polydimethylaminoethylmethacrylate for oral insulin delivery. Polymerization of dimethylaminoethylmethacrylate was carried out in aqueous medium with potassium persulfate as the initiator. Quaternization of the resulting hydrogel was carried out to introduce cationic surface groups and the derivatization was confirmed by zeta potential measurements, nuclear magnetic resonance and infrared spectroscopies. Swelling behavior of these particles was evaluated for dependence of pH. Insulin-loaded particles were subjected to in vitro release experiments at gastric and intestinal pH. Moreover, cytotoxicity evaluation showed that both polydimethylaminoethylmethacrylate and its quaternized derivative were non-toxic to Caco-2 and L929 cell lines. The presence of quaternary ammonium groups improved the cationic charge and enhanced the mucoadhesive properties of the hydrogel. Confocal microscopic observations showed that these sub-microparticles were capable of opening tight junctions between the Caco-2 cells and thus increased the paracellular permeability. The above studies suggest that cationic hydrogel sub-microparticles can act as a good candidate for oral insulin delivery. [ABSTRACT FROM PUBLISHER]

Background Although icodextrin has been shown to augment peritoneal ultrafiltration in peritoneal dialysis (PD) patients, its impact upon other clinical end points, such as technique survival, remains uncertain. This systematic review evaluated the effect of icodextrin use on patient level clinical outcomes. Methods The Cochrane CENTRAL Registry, MEDLINE, Embase and reference lists were searched (last search 13 September 2012) for randomized controlled trials of icodextrin versus glucose in the long dwell exchange. Summary estimates of effect were obtained using a random effects model. Results Eleven eligible trials (1222 patients) were identified. There was a significant reduction in episodes of uncontrolled fluid overload [two trials; 100 patients; relative risk (RR) 0.30, 95% confidence interval (CI) 0.15–0.59] and improvement in peritoneal ultrafiltration [four trials; 102 patients; mean difference (MD) 448.54 mL/day, 95% CI 289.28–607.80] without compromising residual renal function [four trials; 114 patients; standardized MD (SMD) 0.12, 95% CI −0.26 to 0.49] or urine output (three trials; 69 patients; MD −88.88, 95% CI −356.88 to 179.12) with icodextrin use for up to 2 years. There was no significant effect on peritonitis incidence (five trials; 607 patients; RR 0.97, 95% CI 0.76–1.23), peritoneal creatinine clearance (three trials; 237 patients; SMD 0.36, 95% CI −0.24 to 0.96), technique failure (three trials; 290 patients; RR 0.58, 95% CI 0.28–1.20), patient survival (six trials; 816 patients; RR 0.82, 95% CI 0.32–2.13) or adverse events. Conclusions Icodextrin prescription improved peritoneal ultrafiltration, mitigated uncontrolled fluid overload and was not associated with increased risk of adverse events. No effects of icodextrin on technique or patient survival were observed, although trial sample sizes and follow-up durations were limited. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the feasibility of transperineal polyethylene glycol (PEG) hydrogel insertion into anterior perirectal fat for reducing rectal radiation dose in patients with suboptimal rectal dosimetry after permanent iodine-125 prostate brachytherapy. Methods and Materials: Five patients with suboptimal rectal dosimetry after iodine-125 seed brachytherapy implant underwent a single transperineal injection of PEG hydrogel into the anterior perirectal fat under general anesthetic using transrectal ultrasound guidance. Prostate–rectum separation and rectal radiation dose before and after PEG hydrogel spacer insertion were measured. Toxicity because of spacer insertion was assessed at Days 0–1 and 4–6 weeks using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results: All patients experienced a clinically significant reduction in the volume of rectum receiving greater than or equal to the prescription dose (RV 100) on the postspacer postimplant dosimetry, compared with the prespacer postimplant dosimetry. Mean prostate–rectum separation that was achieved with the insertion of the spacer was 15.1 mm (±3.4). The mean difference in separation from before to after spacer insertion was 12.5 mm (±4.5). This was associated with a reduction in mean RV 100 from 3.04 (±1.2) to 0.06 (±0.1) cc. Toxicities were limited to Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0) perineal pain and rectal discomfort (3/5 patients). There were no Grade 2 or greater toxicities reported after insertion of the spacer. Conclusions: PEG hydrogel is safe and effective at reducing rectal radiation dose in select patients with suboptimal rectal dosimetry after prostate seed brachytherapy. [ABSTRACT FROM AUTHOR]

Peptide-based hydrogel nanoparticles represent a promising alternative to current drug delivery approaches. We have previously demonstrated that the Fmoc-FF aromatic dipeptide building block can self-assemble in aqueous solutions to form nano-scaled ordered hydrogels of remarkable mechanical rigidity. Here, we present a scalable process for the assembly of this peptide into hydrogel nanoparticles (HNPs) aimed to be utilized as potential drug delivery carriers. Fmoc-FF based HNPs were formulated via modified inverse-emulsion method using vitamin E-TPGS as an emulsion stabilizer and high speed homogenization. The formed HNPs exhibited two distinguishable populations with an average size of 21.5±1.3 and 225.9±0.8nm. Gold nanoparticles were encapsulated within the hydrogel nanoparticles as contrast agents to monitor the formation of the assemblies and their ultrastructural properties. Next, we demonstrated a robust experimental procedure developed and optimized for the formulation, purification, storage and handling procedures of HNPs. Encapsulation of doxorubicin (Dox) and 5-flourouracil (5-Fu) within the HNPs matrix showed release kinetics of the drugs depending on their chemical structure, molecular weight and hydrophobicity. The results clearly indicate that Fmoc-FF based hydrogel nanoparticles have the potential to be used as encapsulation and delivery system of various drugs and bioactive molecules. [ABSTRACT FROM AUTHOR]

Abstract: Biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration. In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-β3 (TGF-β3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model. The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-β3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-β3 in OPF composite hydrogels. The results of an in vitro release study demonstrated that TGF-β3 release kinetics could be modulated by the GF incorporation method. At 12weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring. All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control. Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-β3, independent of the TGF-β3 release kinetics. The results suggest that although the dual delivery of TGF-β3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Highlights: [•] 2-Step delivery system was prepared by incorporating ceramide liposomes into cellulose hydrogel. [•] Liposome-in-hydrogel complex systems were favorable for the skin permeability than the single systems of hydrogel or liposome. [•] Liposome-in-hydrogel complex systems enhanced transdermal permeation of quercetin and rutin. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we developed a biodegradable and injectable composite drug delivery system (DDS), camptothecine (CPT) loaded polymeric microsphere in thermosensitive hydrogel, for colorectal peritoneal carcinomatosis (CRPC) therapy. In our previous studies, we found that poly(ɛ-caprolactone)–poly(ethylene glycol)–poly(ɛ-caprolactone) (PCL–PEG–PCL, PCEC) copolymers with different molecular weight and PEG/PCL ratio could be administrated to form microsphere or thermosensitive hydrogel, respectively. Therefore, the composite DDS was composed of CPT loaded microsphere (CPT-MS) and thermosensitive hydrogel. CPT-MS was prepared by CPT and PCEC copolymer (M n =31,600) using an oil-in-water emulsion solvent evaporation method. Besides, biodegradable and injectable thermosensitive PCEC hydrogel (M n =3150) with lower sol–gel transition temperature at around body temperature was also prepared. The CPT-MS in thermosensitive hydrogel (CPT-MS/hydrogel) composite is a free-flowing sol at ambient temperature and instantly converts into a non-flowing gel at body temperature. Furthermore, cytotoxicity assay indicated that both microsphere and hydrogel were biocompatible with very low cytotoxicity. In vitro release profile demonstrated a significant difference between rapid release of free CPT and much slower and sustained release of CPT-MS/hydrogel. In addition, intraperitoneal administration of CPT-MS/hydrogel could effectively suppress growth and metastasis of CT26 peritoneal carcinomatosis in vivo, and prolonged the survival of tumor bearing mice. Compared with CPT-MS or free CPT, CPT-MS/hydrogel induced a stronger anti-tumor effect by increasing apoptosis of tumor cells and inhibiting microvessel density of tumor tissue. Besides, side effects of CPT were also alleviated in CPT-MS/hydrogel-treated mice. Thus, our results suggested that CPT-MS/hydrogel may have great potential applications in clinic. [Copyright &y& Elsevier]