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Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. In vitro and in vivo studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, in vitro. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx®) or its combination with elacridar.

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OBJECTIVES: The aim of this study was to compare the radiological and clinical results of femoral diaphyseal fractures operated in the lateral decubitus position with those operated in the supine position on a traction table and to detail the perioperative surgical technique. PATIENTS AND METHODS: Between October 2018 and January 2022, in this prospective, randomized, and single-blind comparative study, 75 patients diagnosed with adult femoral diaphyseal fractures to whom intramedullary nails were applied were operated in the lateral decubitus position without a traction table (Group 1, 37 patients) and in the supine position with a traction table (Group 2, 38 patients). Preoperative age, gender, fracture mechanism, fracture type, and surgical waiting times were determined. Perioperative anesthesia type, surgery preparation time, surgical time, number of fluoroscopy doses, amount of bleeding, and type of reduction were evaluated, and detailed observational descriptions of the surgical techniques were made. In the postoperative period, radiological evaluations were made with x-ray radiography and orthoroentgenogram, while in the clinical evaluation, hip-knee joint range of motion and rotational evaluation were made with the Craigs test. Follow-up periods were determined and complications noted. RESULTS: The average age was 32 in Group 1 and 28 in Group 2, the female/male ratio was 1:36 in Group 1 and 5:33 in Group 2, and the follow-up period was 18.2 months Group 1 and 21.7 months in Group 2. No significant difference was detected between the groups in terms of age, gender, fracture mechanism, fracture type, anesthesia type, surgical waiting time, and follow-up period (p > 0.05). Compared to Group 2, the shorter preparation time, surgical time, and number of fluoroscopy doses in Group 1 were found to be statistically significant (p < 0.05). The differences in the amount of bleeding and need for open reduction were not statistically significant between the groups (p > 0.05), and no statistical difference was found in joint range of motion and rotational evaluation in clinical evaluation in both groups (p > 0.05). There was no significant difference in terms of complications between groups. CONCLUSIONS: We found the lateral decubitus method without a traction table to be a safe and effective alternative to the supine method with a traction table in terms of the radiological and clinical results and that it also has the advantages of shortening the surgical time, reducing radiation exposure. LEVEL OF EVIDENCE: Level 1 prospective, randomized, single-blind controlled study.

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K-RAS is a highly relevant oncogene that is mutated in approximately 90% of pancreatic cancers and 20-25% of lung adenocarcinomas. The aim of this work was to develop a new anti-KRAS siRNA therapeutic strategy through the engineering of functionalized lipid nanoparticles (LNPs). To do this, first, a potent pan anti-KRAS siRNA sequence was chosen from the literature and different chemical modifications of siRNA were tested for their transfection efficacy (KRAS knockdown) and anti-proliferative effects on various cancer cell lines. Second, a selected siRNA candidate was loaded into tLyp-1 targeted and non-targeted lipid nanoparticles (LNPs). The biodistribution and antitumoral efficacy of selected siRNA-loaded LNP-prototypes were evaluated in vivo using a pancreatic cancer murine model (subcutaneous xenograft CFPAC-1 tumors). Our results show that tLyp-1-tagged targeted LNPs have an enhanced accumulation in the tumor compared to non-targeted LNPs. Moreover, a significant reduction in the pancreatic tumor growth was observed when the anti-KRAS siRNA treatment was combined with a classical chemotherapeutic agent, gemcitabine. In conclusion, our work demonstrates the benefits of using a targeting approach to improve tumor accumulation of siRNA-LNPs and its positive impact on tumor reduction.

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INTRODUCTION: This study aimed to compare the radiological and clinical results of VP and EF applications in multi-fragmented radius distal intra-articular fractures (AO type C) in our clinic. METHODS: We retrospectively analysed 80 patients who underwent surgery for radius distal fracture (AO type C) between 2014 and 2020. Group 1 comprised patients who were treated with VP, and Group 2 comprised patients who were treated with EF. Radiological evaluation was performed by measuring radial inclination, radial length, volar tilt, intra-articular step-off and ulnar variance by two-way radiography. The clinical findings were evaluated using the Gartland and Werley scoring system, and complications were noted. RESULTS: There were no statistically significant differences between the two groups in terms of age, gender, side, fracture subtypes and follow-up time (p > 0.05). There were no statistically significant differences between the two groups in radiological parameters (based on cut-off values) (p > 0.05). The clinical evaluation did not reveal a statistically significant difference between the two groups (p = 0.613). CONCLUSION: EF is as successful as VP in providing radiological cut-off values. EF treatment can be used as an effective and safe alternative method for multi-fragmented radius distal intra-articular fractures.

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PURPOSE: It is known that the incidence of paediatric orthopaedic trauma peaks in the summer months as a result of increased and uncontrolled physical activity. The aim of this study was to review the experience of a single centre with paediatric orthopaedic traumas and determine the relationship between the severity and the variations in the incidence of traumas in relation to the seasons and temperatures during the study period. MATERIALS AND METHODS: A single institutional review of the historical data of all patients aged 0-16 years who presented for orthopaedic trauma between January 2018 and December 2020 in the emergency department of Level 1 tertiary orthopaedic trauma centre was conducted. 65,182 paediatric orthopaedic trauma cases had been retrieved from the hospital data base during the 3 -year study period. We classified the traumas according to the variants of the patients' and by holidays, seasons, school days and weekends, months and in which part of the body it occurred. RESULTS: After excluding the summer vacation, 77% of paediatric orthopaedic trauma patients attended to the hospital on weekdays and 23% on weekends. While it was observed that hot weather had a statistically positive effect on trauma attendance, rainy weather had an negative effect (p < 0.05). Trauma attendances were found to be statistically higher in summer months, except for injuries that may occur with indoor activities such as metacarpal fracture, phalanx fracture and pulled elbow (p < 0.05). CONCLUSION: Orthopaedic trauma at a Level 1 tertiary health care trauma center do vary significantly with the weather and are highest in the summer season. Therefore, it should focus more attention on preventive strategies for paediatric trauma in the summer season.

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BACKGROUND: Although pilon fractures are rare, they are important for orthopedic surgeons because of the difficulty of their treatment and their adverse effects on gait function. The aim of this was study to evaluate the relationship between the reduction quality of the fracture, functional results, ankle arthrosis, and plantar pressure distribution in patients with tibia pilon fractures. METHODS: In this study, a total of 62 patients treated for an intraarticular pilon fracture in our clinic between January of 2015 and January of 2019 were evaluated retrospectively. Postoperative reduction qualities of the patients were evaluated with the Ovadia-Beals criteria; ankle functional scores were evaluated with the Teeny-Wiss score; and ankle arthrosis was evaluated with the Takakura classification. At the last patient follow-up, foot loading analysis was performed, and the results were evaluated for their relation with postoperative reduction quality, ankle function, and ankle arthrosis. RESULTS: There were 62 patients (50 men and 12 women). The average age was 43.3 years (range, 19-78 years). The mean follow-up was 34.3 months (range, 24-58 months). The mean Ovadia-Beals score was 12.35 ± 4.6 on the postoperative plain radiographs of the patients; the mean Teeny-Wiss score at the last follow-up was 76.82 ± 17.69; and the mean Takakura score was 1.47 ± 1.35. Based on the pedobarographic measurements, 47.58% of the patients put weight on the anterior portion and 52.42% on the posterior portion of the foot in the anteroposterior plane. In the mediolateral plane, 42.15% loaded on the medial portion of the ankle and 57.85% loaded on the lateral portion of the foot. CONCLUSIONS: Intra-articular tibia pilon fractures can be demonstrated by lateralization of the walking axis and changes in gait patterns and can be associated with clinical outcome.

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BACKGROUND: The aim of the study is to determine the rate of acute kidney injury (AKI) after hip fracture surgery over the age of 80 and to investigate the factors associated with AKI. METHODS: From January 2015 to January 2020, 589 patients who underwent surgery of hip fractures at our institution were retrospectively reviewed. Serum creatinine (sCr) was analysed daily pre- and postoperatively during the hospital stay. Patients were divided into groups; AKI and non-AKI based on KDIGO (Kidney Disease Global Outcomes) criteria. The incidence, risk factors, and mortality of postoperative AKI were investigated. RESULTS: Out of 589 patients, 58 developed an AKI (9.8%). Smoking (p: 0.004), pre and postoperative low albumin level (p < 0.05), pre- and postoperative high potassium level (p < 0.05), pre- and postoperative high urea levels (p < 0.05), high amount of intra-operative bleeding (p: 0.003) and prolonged surgery time (p: 0.003) were found to be risk factors associated with AKI. Although the mortality rate was higher in the AKI group, it was not statistically significant (p > 0.05). CONCLUSION: AKI is a temporary but common complication following hip fracture surgery, which can also be predicted if risk factors are adequately observed. It typically increases the length of hospital stays, mortality and morbidity. LEVEL OF EVIDENCE: Level III evidence, Retrospective comparative study.

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STUDY DESIGN: A quality-control Internet-based study using recognized quality scoring systems. OBJECTIVE: The aim of the study is to evaluate the quality, content and readability of online information on kyphosis. METHODS: The 3 most frequently used search engines were identified and a search for "Kyphosis" was made in each. The 2 reviewers categorized their Web-sites by type, and the quality of each was assessed using well-known scoring systems, including the DISCERN score, JAMA benchmark, GQS, and the kyphosis specific content score. The Flesch-Kincaid grade level (FKGL) was used to assess the readability. The quality of the information was also evaluated according to the presence and absence of the HONcode. RESULTS: Sixty unique Web sites were identified and analyzed. The distribution of the categories was 33 (55%) medical, 22 (36.7%) academic, 2 (3.3%) non-physician, 2 (3.3%) commercial and 1 (1.7%) physician. There wasn't statistically significant difference between the sources in terms of DISCERN, JAMA, GQS and KSC scores (P > 0.05). However, a review of the FKGL scores revealed that the academic-based websites' FKGL score was significantly higher than the medical-based websites (P: 0.007). Also there wasn't statistically significant difference among the DISCERN, JAMA, GQS, KSC, FKRS and FKGL scores of the web-sites according to the HON code's presence (P > 0.05). CONCLUSION: Information about kyphosis on the Internet is of limited quality and low information value. The readability of the online information in our results showed a significantly higher reading level than the sixth grade level recommended by the AMA and NIH.

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Background: Distal chevron osteotomy (DCO) is commonly performed in hallux valgus surgery. The fixation of the osteotomy is provided by various implants. The usage of biodegradable implants such as magnesium is gradually increasing due to the advantages they provide. In this study, we aimed to compare the fixation of DCO with magnesium or titanium screw biomechanically. Methods: Twenty sawbones were used. The samples were divided into two equal groups, including ten sawbones for fixation with single headless titanium (group-1) or magnesium screw (group-2). DCO and screw fixations were performed on all samples using the same technique. Biomechanical testing was applied to five samples in each group in cantilever and the other five in a physiological configuration using a computer connected to the electromechanical test machine. The obtained data were evaluated using the Shapiro-Wilk test, Student's t-test and Mann-Whitney U test on the IBM® SPSS (Statistical Package for the Social Sciences) V22.0 software. Significance was accepted at the p < 0.05 level. Results: There was no statistically significant difference between the magnesium screw and the titanium screw in terms of maximum force, maximum displacement and stiffness measurements in cantilever and physiological loadings (p > 0.05 for all). Conclusion: This study found no significant difference in biomechanical stability between the magnesium and titanium screws in DCO fixation on sawbones. Further studies with real bones are needed.

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BACKGROUND: This present study was designed to evaluate the effect of restrictions on fracture admission to a Level-1 tertiary trauma hospital between COVID-19 pandemic and pre-pandemic restriction time intervals that included groups of younger than <20-years-old, 20-65-years-old, and older than aged >65-years-old. METHODS: Patients who were hospitalized and treated for orthopedic treatment between 10 March and 1 June during the pandemic period were retrospectively analyzed. Control group consisted of patients admitted to the hospital in the same time interval in 2019. The patients were divided into three groups, under 20 years of age, between 20 and 65 years of age, and over 65 years of age. The patients' data included age, gender, trauma mechanism, fracture type, and any COVID-19 radiological or clinical symptoms. RESULTS: The number of patients >65-years-old admitted to the orthopedic trauma center was high at pandemic intervals compared to pre-pandemic time. When the groups were compared for patients of 20-65-years-old; there was a significant difference for the fracture type (p<0.05). Lower extremity fractures were high at pre-pandemic group, whereas multiple traumas were high at pandemic group. For sub-group 20-65 ages, low-energy traumas were higher at pre-pandemic group, whereas high-energy traumas were more frequent at the pandemic group. CONCLUSION: We observed a decrease in fracture admission to orthopedic trauma centers during COVID-19 pandemic for subgroups of <20-years-old and 20-65-years-old ages, whereas there was a significant increase for >65-years-old age, most of them related to the osteoporotic hip fractures. So that older age group should be encouraged to mobilize at home and have permission to walk and make physical activity to avoid osteoporosis for a limited time daily.

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AIM: To evaluate the surgical outcomes and complications of patients over 65 years of age, with unstable ankle fractures. MATERIAL AND METHOD: The study included 111 patients (73F/38 M) operated on between January 2015 and February 2019 and followed up for a mean of 21.2 months (range, 6-62 months).Demographic characteristics, comorbidities, fracture type, and mechanisms of injury were evaluated. Relationships between postoperative complications and comorbidities were examined. In the postoperative functional evaluations, the AOFAS score was used and pre and postoperative mobilization (eg, use of assistive devices) was assessed. RESULTS: The mean age of the patients was 70.5 ± 6.1 years (range, 65-90 years). The mechanism of trauma was low-energy trauma in 90.1% of the fractures and high-energy trauma in 9.9%. The fractures were formed with a SER injury (supination external rotation) in 83.7% of cases and bimalleolar fractures were seen most frequently (85/111, 76%).Complications developed in 16 (14.4%) patients and a second operation was performed in 11 (9.9%) patients with complications. Plate was removed and debridement was performed in 5 of 6 patients due to wound problems. Nonunion was developed in the medial malleolus in 4 patients. Revision surgery was performed because of implant irritation in 2 patients and early fixation loss in the medial malleolus fracture in one patient. Calcaneotibial arthrodesis was performed in 3 patients because of implant failure and ankle luxation associated with non-union. A correlation was determined between ASA score and DM and complications, but not with osteoporosis. The mean follow-up AOFAS score was 86.7 ± 12.5 (range, 36-100).A total of 94 (84.7%) patients could walk without assistance postoperatively and 92 (82.9%) were able to regain the preoperative level of mobilization. CONCLUSION: Although surgery can be considered an appropriate treatment option for ankle fractures in patients aged >65 years, care must be taken to prevent potential complications and the necessary precautions must be taken against correctable comorbidities.

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Aim This study aims to analyze the spectrum, management, and outcome of Syrian refugees' fracture over four-year period, highlighting challenges in management and follow-up. Methods This was a retrospective review of Syrian refugee patients operated for fractures at our centre from January 2015 to January 2019. The patients were evaluated for age, gender, mechanism of injury, location and type of fracture, presence of accompanying injuries, surgical technique, complications, mortality and morbidity. The comparison of complications and postop outpatient clinic controls between Turkish citizens and Syrian refugees were also evaluated. Results The study included a total of 455 patients comprising 281 adults (202 males, 79 females) with a mean (SD) age of 41.1 (19.3) years and 174 children with a mean age of 8.8 (4.9) years. The trauma mechanism was most commonly fall in both adult and pediatric patients (86.6% / 73.5%). Whilst lower limb fractures were more common in adults (73.7%), upper limb fractures were more common in children (63.4%). The presence of accompanying trauma was determined in 21 (7.5%) adults and 10 (5.7%) children. Multiple fractures were determined in 12 (4.3%) adults and eight (4.6%) children. Plate fixation (PF) was most used in 137 (48.8%) adult patients and K-wire augmentation was used in 75 (43.1%) pediatric patients. Out of the 455 patients, 41 (14.6%) adults and 13 (7.3%) children developed complications. Whilst three adult patients were died during follow-up, no deaths were recorded in the pediatric patients. Complication rate was 54/455 in Syrian refugees and 32/455 in citizens. It was observed that the complication was significantly higher in immigrants (p: 0.017). Sixty-five (14.2%) Syrian immigrants did not come to the outpatient clinic control at all or once, while this rate was 29/455 (6.3%) for Turkish citizens (p = 0.012). Conclusion Inadequate living conditions and lack of communication faced by refugees reduce the rate of patient follow-up and negatively affect the results of orthopedic trauma.

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BACKGROUND: The aim of this study was to compare the outcomes of unstable intertrochanteric femur fractures treated with cementless calcar-replacement bipolar hemiarthroplasty (CRH) and proximal femoral nail (PFN) in elderly patients. METHODS: All consecutive unstable intertrochanteric fractures treated with cementless CRH or PFN at our institution between January 2015 and January 2019 were reviewed retrospectively. The primary outcome measures were postoperative complications, reoperation rate, and hip function. The secondary outcome measures were intraoperative blood loss, transfusion rate, surgical time, hospital stay, and two- year mortality. RESULTS: Ninety-four patients in the hemiarthroplasty group and 77 patients in the PFN group were included for analysis. There were no significant differences between the two groups regarding the complications, ASA score, and reoperation rate. Significant differences were found between hemiarthroplasty and PFN group in comparison of the average length of hospital stay (P < 0.05), time from hospitalization to operation (P < 0.05), intraoperative blood loss (P < 0.001), transfusion rate (P < 0.001), operation time (P < 0.001), Harris Hip Score (HHS; P < 0.001), and two-year mortality (P < 0.05). CONCLUSION: Both hemiarthroplasty and PFN produce satisfactory results in surgically treated unstable intertrochanteric femur fractures in the elderly. Both groups are associated with their own complications, but in the PFN group, better functional results, less surgery-related trauma, and lower mortality rates are the main advantages.

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BACKGROUND: Although Kirschner wire implantation is popular for treating toe deformities, complications frequently occur. To prevent pin-tract infection and difficult Kirschner wire extraction, several implants have been developed to improve treatment outcomes. METHODS: Patients who had undergone an interphalangeal fusion by two-component implant for the treatment of toe deformities were included. Thirty-one toes of 21 patients were evaluated retrospectively. American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores were used in clinical evaluation. RESULTS: The mean operation duration per toe was 16.4 min (range, 13-26 min). The average AOFAS forefoot score was 42.76 (range, 23-57) preoperatively and 88.76 (range, 70-95) at 34.4 months (range, 26-46 months) after surgery. Mean follow-up was 14.8 months (range, 12-19 months). Compared with before surgery, the AOFAS score was increased significantly after surgery (P = .03 by t test). Three minor complications were encountered. In one patient an infection was observed. After the implants were removed (first month) she was treated successfully by debridement and antibiotic agents and, finally, Kirschner wire placement. The second patient had a fissure fracture at the proximal phalanx, but routine follow-up did not change. In the third patient, the locking mechanism had become loose (detected on day 1 radiography); it was remounted under fluoroscopy without opening the wound. No patients had a cutout, loss of alignment, recurrence, or persistent swelling. CONCLUSIONS: Outcomes of arthrodesis using the two-component implant were found to be safe and reliable, especially for hammer toe and fifth toe deformities.

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OBJECTIVES: This study aims to compare the results of internal fixation with dynamic hip screw (DHS)/antirotation screw and conventional cannulated screw (CS) for femoral neck fracture. PATIENTS AND METHODS: This retrospective study included a total of 78 patients (57 males, 21 females) with collum femoris fractures treated with internal fixation between January 2015 and January 2019. Group 1 comprised 41 patients with a mean age of 45.7 years (range, 19 to 62 years) treated with DHSs/antirotation screws, while group 2 comprised 37 patients with a mean age of 41.9 years (range, 17 to 75 years) treated with CSs. The patients were evaluated for union, avascular necrosis (AVN), femoral neck shortness, operation time, duration of fluoroscopy exposure, and functional outcomes. RESULTS: Age, gender, and Garden classification stages were similar in both groups. No significant difference was found between the groups in respect of AVN and non-union rates. The non-union rate was 12.2% in group 1 and 21.6% in group 2 (p>0.05). The duration of fluoroscopy exposure was statistically significantly higher in group 2 (p=0.001) and the operation time was statistically significantly longer in group 1 (p=0.001). In group 2, femoral neck shortness stature was significantly higher (p=0.007). At the final follow-up examination, the Harris hip score was statistically significantly higher in group 1 (p=0.04). CONCLUSION: Dynamic hip screw/antirotation screw was a more relevant treatment method for transcervical femoral neck fractures compared to CS with more favorable functional outcomes and less fluoroscopy exposure.

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Malignant gliomas are highly lethal. Delivering chemotherapeutic drugs to the brain in sufficient concentration is the major limitation in their treatment due to the blood-brain barrier (BBB). Drug delivery systems may overcome this limitation and can improve the transportation through the BBB. Paclitaxel is an antimicrotubule agent with effective anticancer activity but limited BBB permeability. R-Flurbiprofen is a nonsteroidal antienflammatory drug and has potential anticancer activity. Accordingly, we designed an approach combining R-flurbiprofen and paclitaxel and positively-charged chitosan-modified poly-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) and to transport them to glioma tissue. NPs were characterized and, cytotoxicity and cellular uptake studies were carried out in vitro. The in vivo efficacy of the combination and formulations were evaluated using a rat RG2 glioma tumor model. Polyethylene glycol (PEG) modified and chitosan-coated PLGA NPs demonstrated efficient cytotoxic activity and were internalized by the tumor cells in RG2 cell culture. In vivo studies showed that the chitosan-coated and PEGylated NPs loaded with paclitaxel and R-flurbiprofen exhibited significantly higher therapeutic activity against glioma. In conclusion, PLGA NPs can efficiently carry their payloads to glioma tissue and the combined use of anticancer and anti-inflammatory drugs may exert additional anti-tumor activity.

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Infection with the human immunodeficiency virus (HIV) is affecting women disproportionally with increasing incidence rates over the last decades. Tenofovir is one of the most commonly used antiretroviral agents, which belongs to the nucleoside/nucleotide reverse transcriptase inhibitor family, for the prevention of HIV acquisition. In scope of this study, a thermogelling system containing tenofovir-loaded chitosan nanoparticles for the controlled release of tenofovir was developed and characterized. The in vitro release studies have shown that the burst release effect was decreased to 27% with f-TFV CS NPs-Gel. Gelation temperature of developed formulation was found as 26.6 ± 0.2 °C, which provides ease of administration while gelation occurs after the administration to the vagina. The work of adhesion values was used as parameters for comparison of mucoadhesive performance and the mucoadhesion of f-TFV CS NPs-Gel was found as 0.516 ± 0.136 N.s at 37 °C. The biocompatibility of blank formulations was evaluated by cell viability studies using L929 cells, in which Gel + CS NPs formulation was found to be safe with 82.4% and 90.2% cell viability for 1:16 and 1:32 dilutions, respectively. In conclusion, an improved tenofovir containing vaginal gel formulation was successfully developed and evaluated for preventing HIV transmission.

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The blood-brain barrier (BBB) is the major problem for the treatment of central nervous system diseases. A previous study from our group showed that the brain-targeted chitosan nanoparticles-loaded with large peptide moieties can rapidly cross the barrier and provide neuroprotection. The present study aims to determine the efficacy of the brain-targeted chitosan nanoparticles' uptake by the human BBB cerebral microvessel endothelial cells (hCMECs) and to investigate the underlying mechanisms for enhanced cellular entry. Fluorescently labelled nanoparticles either conjugated with antibodies recognising human transferrin receptor (anti-TfR mAb) or not were prepared, characterised and their interaction with cerebral endothelial cells was evaluated. The antibody decoration of chitosan nanoparticles significantly increased their entry into hCMEC/D3 cell line. Inhibition of cellular uptake by chlorpromazine indicated that the anti-TfR mAb-conjugated nanoparticles were preferentially cell internalised through receptor-mediated endocytosis pathway. Alternatively, as primarily observed with control chitosan nanoparticles, aggregation of nanoparticles may also have induced macropinocytosis.

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In this study, it was aimed to investigate characteristics and intracellular delivery of two different-sized PLGA nanoparticles in ouzo region by considering number of nanoparticles. To determine the effect of formulation parameters on average particle size, Dil labeled nanoparticles were prepared using a three-factor, two-level full factorial statistical experimental design. PLGA230 (230.8 ± 4.32 nm) and PLGA160 (157.9 ± 6.16 nm) nanoparticles were obtained by altering polymer amount based on experimental design results and characterized. Same number of PLGA230 and PLGA160 nanoparticles per cell were applied onto HEK293 cells; then, cytotoxicity, uptake kinetics and mechanism were evaluated by flow cytometry and fluorescent microscopy. Also same weight of PLGA230 and PLGA160 nanoparticles were applied and cellular uptake of these nanoparticles was evaluated. It was found that PLGA230 nanoparticles had higher encapsulation efficiency and slower dye release compared to PLGA160 nanoparticles. When they were applied at same counts per cell, PLGA230 nanoparticles displayed faster and higher intracellular dye transfer than PLGA160 nanoparticles. On the other hand, PLGA160 appeared to be a more effective vehicle than PLGA230 when applied at the same weight concentration. It was also shown that for both nanoparticles, HEK293 cells employed macropinocytic, caveolae- and clathrin-mediated endocytic pathways.

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BACKGROUND: The incidence of fractures in the trochanteric area has risen with the increasing numbers of elderly people with osteoporosis. Although dynamic hip screw fixation is the gold standard for the treatment of stable intertrochanteric femur fractures, treatment of unstable intertrochanteric femur fractures still remains controversial. Intramedullary devices such as Gamma nail or proximal femoral nail and proximal anatomic femur plates are in use for the treatment of intertrochanteric femur fractures. There are still many investigations to find the optimal implant to treat these fractures with minimum complications. For this reason, we aimed to perform a biomechanical comparison of the proximal femoral nail and the locking proximal anatomic femoral plate in the treatment of unstable intertrochanteric fractures. MATERIALS AND METHODS: Twenty synthetic, third generation human femur models, obtained for this purpose, were divided into two groups of 10 bones each. Femurs were provided as a standard representation of AO/Orthopedic Trauma Associationtype 31-A2 unstable fractures. Two types of implantations were inserted: the proximal femoral intramedullary nail in the first group and the locking anatomic femoral plate in the second group. Axial load was applied to the fracture models through the femoral head using a material testing machine, and the biomechanical properties of the implant types were compared. RESULT: Nail and plate models were locked distally at the same level. Axial steady load with a 5 mm/m velocity was applied through the mechanical axis of femur bone models. Axial loading in the proximal femoral intramedullary nail group was 1.78-fold greater compared to the plate group. All bones that had the plate applied were fractured in the portion containing the distal locking screw. CONCLUSION: The proximal femoral intramedullary nail provides more stability and allows for earlier weight bearing than the locking plate when used for the treatment of unstable intertrochanteric fractures of the femur. Clinicians should be cautious for early weight bearing with locking plate for unstable intertrochanteric femur fractures.