Search results for: implant assisted-magnetic drug targeting (IA-MDT)

Authors: Mayur Chaudhari, Ashutosh Gaikwad, Shubham Kavathale, Aditya Mule, Dilip Panchal, Puja Verma

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The purpose of this investigation was to locate restorative bio-materials for the manufacture of implants and crowns. A three-dimensional (3D) finite element analysis (FEA) was carried out to evaluate the stress distribution in the implant and abutment with several types of bio-materials and various prosthetic crowns. While the dental implant, abutment, and screw were subjected to a vertical impact force, the effects of mechanical characteristics such as Young's modulus and Poisson's ratio were evaluated and contrasted. Crowns are made from zirconia, cobalt, ceramic, acrylic resin, and porcelain materials. Implants are made from materials such as titanium, zirconia, PEEK, and CFR-PEEK. SolidWorks was used to create the 3D geometry, and Ansys Software was used to analyze it. The results show that using CFR-PEEK implants and an acrylic resin crown resulted in less bone stress than using alternative materials. In order to reduce the amount of stress on the bone and possibly prevent implant failure, the study's findings support the use of a CFR PEEK implant, abutment, and crown in bruxism patients.

Keywords: biomaterials, implant, crown, abutment

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Authors: Ardiansyah I. Ryan, Ashsholih K. R., Fathurrohman G. R., Kurniadi M. R., Huda P. A

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The burden of brain-related disease is very high. There are a lot of brain-related diseases with limited treatment result and thus raise the burden more. The Parkinson Disease (PD), Mental Health Problem, or Paralysis of extremities treatments had risen concern, as the patients for those diseases usually had a low quality of life and low chance to recover fully. There are also many other brain or related neural diseases with the similar condition, mainly the treatments for those conditions are still limited as our understanding of the brain function is insufficient. Brain Implant Technology had given hope to help in treating this condition. In this paper, we examine the current update of the brain implant technology. Neurotechnology is growing very rapidly worldwide. The United States Food and Drug Administration (FDA) has approved the use of Deep Brain Stimulation (DBS) as a brain implant in humans. As for neural implant both the cochlear implant and retinal implant are approved by FDA too. All of them had shown a promising result. DBS worked by stimulating a specific region in the brain with electricity. This device is planted surgically into a very specific region of the brain. This device consists of 3 main parts: Lead (thin wire inserted into the brain), neurostimulator (pacemaker-like device, planted surgically in the chest) and an external controller (to turn on/off the device by patient/programmer). FDA had approved DBS for the treatment of PD, Pain Management, Epilepsy and Obsessive Compulsive Disorder (OCD). The target treatment of DBS in PD is to reduce the tremor and dystonia symptoms. DBS has been showing the promising result in animal and limited human trial for other conditions such as Alzheimer, Mental Health Problem (Major Depression, Tourette Syndrome), etc. Every surgery has risks of complications, although in DBS the chance is very low. DBS itself had a very satisfying result as long as the subject criteria to be implanted this device based on indication and strictly selection. Other than DBS, there are several brain implant devices that still under development. It was included (not limited to) implant to treat paralysis (In Spinal Cord Injury/Amyotrophic Lateral Sclerosis), enhance brain memory, reduce obesity, treat mental health problem and treat epilepsy. The potential of neurotechnology is unlimited. When brain function and brain implant were fully developed, it may be one of the major breakthroughs in human history like when human find ‘fire’ for the first time. Support from every sector for further research is very needed to develop and unveil the true potential of this technology.

Keywords: brain implant, deep brain stimulation (DBS), deep brain stimulation, Parkinson

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Authors: Pooja Mongia Raj, Rakesh Raj, Alpana Ram

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Background: The use of multiparticulate drug delivery systems in preference to single unit dosage forms for colon targeting purposes dates back to 1985 when Hardy and co-workers showed that multiparticulate systems enabled the drug to reach the colon quickly and were retained in the ascending colon for a relatively long period of time. Methods: Site-specific colonic drug delivery system (nanoparticles) of 5-ASA were prepared and coated with pH sensitive polymer. Chitosan nanoparticles (CTNP) bearing 5-Amino salicylic acid (5-ASA) were prepared, by ionotropic gelation method. Nanoparticulate dosage form consisting of a hydrophobic core enteric coated with pH-dependent polymer Eudragit S-100 by solvent evaporation method, for the effective delivery of drug to the colon for treatment of ulcerative colitis. Results: The mean diameter of CTNP and ECTNP formulations were 159 and 661 nm, respectively. Also optimum value of polydispersity index was found to be 0.249 [count rate (kcps) was 251.2] and 0.170 [count rate (kcps) was 173.9] was obtained for both the formulations respectively. Conclusion: CTNP and Eudragit chitosan nanoparticles (ECTNP) was characterized for shape and surface morphology by scanning electron microscopy (SEM) appeared to be spherical in shape. The in vitro drug release was investigated using USP dissolution test apparatus in different simulated GIT fluids showed promising release. In vivo experiments are in further proceeding for fruitful results.

Keywords: colon targeting, nanoparticles, polymer, 5-amino salicylic acid, edragit

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Authors: Dr., Suchita Daokar

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Background: Successful orthodontic treatment has always relied on anchorage. The stability of the implants depends on bone quantity, mini-implant design, and placement conditions. Out of the various methods of gaining stability, Platelet concentrations are gaining popularity for various reasons. PRF is a minimally invasive method, and there are various studies that has shown its role in enhancing the stability of general implants. However, there is no literature found regarding the effect of PRF in enhancing the stability of the orthodontic implant. Therefore, this study aimed to evaluate and assess the efficacy of PRF on the stability of the orthodontic implant. Methods: The study comprised of 9 subjects aged above 18 years of age. The split mouth technique was used; Group A (where implants were coated before insertion) and group B (implant were normally inserted). The stability of the implant was measured using resonance frequency analysis at insertion (T0), 24 hours (T1), 2 weeks (T2), at 4 weeks (T3), at 6 weeks (T4), and 8 weeks (T5) after insertion. Result: Statistically significant findings were found when group A was compared to group B using ANOVA test (p<0.05). The stability of the implant of group A at each time interval was greater than group B. The implant stability was high at T0 and reduces at T2, and increasing through T3 to T5. The stability was highest at T5. Conclusion: A chairside, minimally invasive procedure ofPRF coating on implants have shown promising results in improving the stability of orthodontic implants and providing scope for future studies.

Keywords: Orthodontic implants, stablity, resonance Frequency Analysis, pre

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Authors: Simona Dostalova, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Protein apoferritin seems to be a very promising structure for use as a nanocarrier. It is prepared from intracellular ferritin protein naturally found in most organisms. The role of ferritin proteins is to store and transport ferrous ions. Apoferritin is a hollow protein cage without ferrous ions that can be prepared from ferritin by reduction with thioglycolic acid or dithionite. The structure of apoferritin is composed of 24 protein subunits, creating a sphere with 12 nm in diameter. The inner cavity has a diameter of 8 nm. The drug encapsulation process is based on the response of apoferritin structure to the pH changes of surrounding solution. In low pH, apoferritin is disassembled into individual subunits and its structure is “opened”. It can then be mixed with any desired cytotoxic drug and after adjustment of pH back to neutral the subunits are reconnected again and the drug is encapsulated within the apoferritin particles. Excess drug molecules can be removed by dialysis. The receptors for apoferritin, SCARA5 and TfR1 can be found in the membrane of both healthy and cancer cells. To enhance the specific targeting of apoferritin nanocarrier, it is possible to modify its surface with targeting moieties, such as antibodies. To ensure sterically correct complex, we used a a peptide linker based on a protein G with N-terminus affinity towards Fc region of antibodies. To connect the peptide to the surface of apoferritin, the C-terminus of peptide was made of cysteine with affinity to gold. The surface of apoferritin with encapsulated doxorubicin (ApoDox) was coated either with gold nanoparticles (ApoDox-Nano) or gold (III) chloride hydrate reduced with sodium borohydride (ApoDox-HAu). The applied amount of gold in form of gold (III) chloride hydrate was 10 times higher than in the case of gold nanoparticles. However, after removal of the excess unbound ions by electrophoretic separation, the concentration of gold on the surface of apoferritin was only 6 times higher for ApoDox-HAu in comparison with ApoDox-Nano. Moreover, the reduction with sodium borohydride caused a loss of doxorubicin fluorescent properties (excitation maximum at 480 nm with emission maximum at 600 nm) and thus its biological activity. Fluorescent properties of ApoDox-Nano were similar to the unmodified ApoDox, therefore it was more suited for the intended use. To evaluate the specificity of apoferritin modified with antibodies, we used ELISA-like method with the surface of microtitration plate wells coated by the antigen (goat anti-human IgG antibodies). To these wells, we applied ApoDox without targeting antibodies and ApoDox-Nano modified with targeting antibodies (human IgG antibodies). The amount of unmodified ApoDox on antigen after incubation and subsequent rinsing with water was 5 times lower than in the case of ApoDox-Nano modified with targeting antibodies. The modification of non-gold ApoDox with antibodies caused no change in its targeting properties. It can therefore be concluded that the demonstrated procedure allows us to create nanocarrier with enhanced targeting properties, suitable for nanomedicine.

Keywords: apoferritin, doxorubicin, nanocarrier, targeting antibodies

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Authors: Xing Wang, Lin Feng, Lingling E., Hongchen Liu

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In patients with type 2 diabetes mellitus (DM) there is poorer quality osseointegration than in non-diabetic (n-DM) patients, and the success of dental implants is less. Recent studies have demonstrated that insulin could stimulate bone cells to produce and accelerate implant osseointegration in DM patients.This raised the question whether insulin could provide local bone anabolic effects in non-diabetic patients. In this study,48 SD rats were divided into four groups randomly: DM group, DM+insulin group, n-DM group, n-DM + insulin group. All rats were implanted the titanium implant near the epiphyseal end of tibia, then the DM + insulin and n-DM + insulin group received twice-daily subcutaneous injections of insulin (10U/day).Two,four and eight weeks after implantation, rats were killed in batches. Histomorphometry and immunohistochemistry were used to evaluate bone formation and osseointegration. The amount of newly formed bone, Implant–bone contact and the expression of OCN,RUNX2 in the DM+insulin, n-DM and n-DM+insulin group were significantly more than in the DM group (p<0.05). Compared with the n-DM group,the Implant–bone contact and expression of OCN,RUNX2 were significantly increased in n-DM+insulin group (p< 0.05). Taken together,these observations provide evidence that insulin has the potential to increase bone formation and osseointegration around implant not only in diabetic subjects but also in non-diabetic subject.

Keywords: insulin, diabetes mellitus, osseointegration, dental implants

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Authors: Jichan Jang

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Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. In this study, we screened the library to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indication of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Thus, we found that compound X, identified, may be a promising candidate in the M. abscessus drug discovery pipeline.

Keywords: Mycobacterium abscessus, antibiotics, drug discovery, emerging Pathogen

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Ahmed Mohamed El-Shamy, Akram Abbas El-Awady, Mahmoud Taha Eldestawy

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Background: The present study was to evaluate clinically and radiographically the combined effect of split crest technique by ultrasonic bone surgery and platelet concentrates in implant site development. Methods: Forty patients with narrow ridge were participated in this study. Patients were assigned randomly into one of the following four groups according to treatment: Group 1: Patients received split-crest technique by ultrasonic bone surgery with implant placement. Group 2: Patients received split-crest technique by ultrasonic bone surgery with implant placement and PRF. Group 3: Patients received split-crest technique by ultrasonic bone surgery with implant placement and PRP. Group 4: Patients received split-crest technique by ultrasonic bone surgery with implant placement and collagen membrane. Modified plaque index, modified sulcus bleeding index, and implant stability were recorded as a baseline and measured again at 3 and 6 months. CBCT scans were taken immediately after surgery completion and at 9 months to evaluate bone density at the bone-implant interface. Results after 6 months; collagen group showed statistically significantly lower mean modified bleeding index than the other groups. After 3 months, the PRF group showed statistically significantly higher mean implant stability with ostell ISQ units' than the other groups. After 6 months, the PRF group showed statistically significantly higher mean implant stability with ostell ISQ units' than the other groups. After 6 months, the PRF group showed statistically significantly higher mean bone density than the collagen group. Conclusion: Ultrasonic bone surgery in split-crest technique can be a successful option for increasing implant stability values throughout the healing period. The use of a combined technique of ultrasonic bone surgery with PRF and simultaneous implant placement potentially improves osseointegration (bone density). PRF membranes represent advanced technology for the stimulation and acceleration of bone regeneration.

Keywords: dental implants, split-crest, PRF, PRP

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Authors: Wessam H. Abd-Elsalam, Mona M. Saber, Samar M. Abouelatta

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Non-steroidal anti-inflammatory drugs (NSAIDs) are considered a double edged sword in inflammatory bowel diseases (IBDs). Some studies reported their advantageous effect in decreasing inflammation, and other studies reported that their use is associated with colitis aggravation. This study aimed to use specifically formulated trehalose-based nano-carriers that targets the colon in an attempt to alleviate inflammation caused by NSAIDs. L-α-phosphatidylcholine (PL), trehalose, and transcutol were used to prepare the trehalosomes (THs), which were also loaded with Tenoxicam(TXM) as a model NSAID. To optimize the formulation variables, a full 23 factorial design, using Design-Expert® software, was performed. The optimized formulation composed of trehalose: PL at a weight ratio of 1:1, 377.72 mg transcutol, and sonicated for 4 min, possessed a spherical shape with a size of 268.61 nm and EE% of 97.83% and released 70.22% of its drug content over 24 h. The superior protective action of TXM loaded THs compared to TXM suspension and drug-free THs was shown by the inhibition of the inflammatory biomarkers, namely; IL-1ß, IL-6, and TNF-alpha levels, as well as oxidative stress markers, measured as GSH and MDA. Improved histopathology of the colonic tissue in male New Zealand rabbits also confirmed the superiority of the TXM loaded THs compared to the unformulated drug or the drug free nano-carriers. Our findings highlight the prosperous role of THs in colon targeting and its anti-inflammatory characteristics in guarding against possible NSAIDs-driven exacerbation of colitis.

Keywords: inflammatory bowel disease, trehalose, trehalosomes, colon targeting

Procedia PDF Downloads 105

Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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Authors: Mohammad ASadian, Samira RajiAsadabadi

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Osteoporosis is very common, particularly in post-menopausal women and is characterized by a decrease in bone mass and strength. Osteoporosis also affects the jawbone and it is considered a potential contraindication to the placement of dental implants. The present paper reviews the literature regarding the effect of osteoporosis on the osseointegration of implants. Experimental models have shown that osteoporosis affects the process of osseointegration, which can be reversed by treatment. However, studies in subjects with osteoporosis have shown no differences in the survival of the implants compared to healthy individuals. Therefore, osteoporosis cannot be considered a contraindication for implant placement. Oral bisphosphonates are the most commonly used pharmacological agents in the treatment of osteoporosis. Although there have been cases of osteonecrosis of the jaw in patients treated with bisphosphonates, they are very rare and it is more usually associated with intravenous bisphosphonates in patients with neoplasms or other serious diseases. Nevertheless, patients treated with bisphosphonates must be informed in writing about the possibility of this complication and must give informed consent. Ceasing to use of bisphosphonates before implant placement does not seem to be necessary.

Keywords: Osteoporosis, dental implant, bisphosphonates, survival

Procedia PDF Downloads 61

Authors: Raviporn Madarasmi, Anjalee Vacharaksa, Pravej Serichetaphongse

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The host response in peri-implant tissue may differ from that in periodontal tissue in a healthy individual. The purpose of this study is to investigate the expression of inflammatory cytokines in peri-implant crevicular fluid (PICF) from single implant with different abutment types in comparison to healthy periodontal tissue. 19 participants with healthy implants and teeth were recruited according to inclusion and exclusion criteria. PICF and gingival crevicular fluid (GCF) was collected using sterile paper points. The expression level of inflammatory cytokines including IL-1α, IL-1β, TNF-α, IFN-γ, IL-6, and IL-8 was assessed using enzyme-linked immunosorbent assay (ELISA). Paired t test was used to compare the expression levels of inflammatory cytokines around natural teeth and peri-implant in PICF and GCF of the same individual. The Independent t-test was used to compare the expression levels of inflammatory cytokines in PICF from titanium and UCLA abutment. Expression of IL-6, TNF-α, and IFN-γ in PICF was not statistically different from GCF among titanium and UCLA abutment group. However, the level of IL-1α in the PICF from the implants with UCLA abutment was significantly higher than GCF (P=0.030). In addition, the level of IL-1β in PICF from the implants with titanium abutment was significantly higher than GCF (P=0.032). When different abutment types was compared, IL-8 expression in PICF from implants with UCLA abutment was significantly higher than titanium abutment (P=0.003).

Keywords: abutment, dental implant, gingival crevicular fluid and peri-implant crevicular fluid

Procedia PDF Downloads 159

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

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The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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Authors: Cho Ee Ng, Hazem Khout, Tarannum Fasih

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Acellular dermal matrices are increasingly used to reinforce the lower pole of the breast during implant breast reconstruction. There is no standard technique described in literature for the use of this product. In this article, we share our operative method of fixation.

Keywords: strattice, acellular dermal matric, breast reconstruction, implant

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Authors: Jamboor K. Vishwanatha

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Among the potent anti-cancer agents, curcumin has been found to be very efficacious against various cancer cells. Despite multiple medicinal benefits of curcumin, poor water solubility, poor physiochemical properties and low bioavailability continue to pose major challenges in developing a formulation for clinical efficacy. To improve its potential application in the clinical area, we formulated poly lactic-co-glycolic acid (PLGA) nanoparticles. The PLGA nanoparticles were formulated using solid-oil/water emulsion solvent evaporation method and then characterized for percent yield, encapsulation efficiency, surface morphology, particle size, drug distribution within nanoparticles and drug polymer interaction. Our studies showed the successful formation of smooth and spherical curcumin loaded PLGA nanoparticles with a high percent yield of about 92.01±0.13% and an encapsulation efficiency of 90.88±0.14%. The mean particle size of the nanoparticles was found to be 145nm. The in vitro drug release profile showed 55-60% drug release from the nanoparticles over a period of 24 hours with continued sustained release over a period of 8 days. Exposure to curcumin loaded nanoparticles resulted in reduced cell viability of cancer cells compared to normal cells. We used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of curcumin to various cancer cells. Functionalized nanoparticles for antibody/targeting agent conjugation was prepared using a cross-linking ligand, bis(sulfosuccinimidyl) suberate (BS3), which has reactive carboxyl group to conjugate efficiently to the primary amino groups of the targeting agents. In our studies, we demonstrated successful conjugation of antibodies, Annexin A2 or prostate specific membrane antigen (PSMA), to curcumin loaded PLGA nanoparticles for targeting to prostate and breast cancer cells. The percent antibody attachment to PLGA nanoparticles was found to be 92.8%. Efficient intra-cellular uptake of the targeted nanoparticles was observed in the cancer cells. These results have emphasized the potential of our multifunctional curcumin nanoparticles to improve the clinical efficacy of curcumin therapy in patients with cancer.

Keywords: polymeric nanoparticles, cancer therapy, sustained release, curcumin

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Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

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Authors: Camilla Trevor, Matthew K. Higgins, Andrea Gonzalez-Munoz, Mark Carrington

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Trypanosomiasis is a devastating disease affecting both humans and livestock in sub-Saharan Africa. The diseases are caused by infection with African trypanosomes, protozoa transmitted by tsetse flies. Treatment currently relies on the use of chemotherapeutics with ghastly side effects. Here, we describe the development of effective antibody-drug conjugates that target the T. brucei transferrin receptor. The receptor is essential for trypanosome growth in a mammalian host but there are approximately 12 variants of the transferrin receptor in the genome. Two of the most divergent variants were used to generate recombinant monoclonal immunoglobulin G using phage display and we identified cross-reactive antibodies that bind both variants using phage ELISA, fluorescence resonance energy transfer assays and surface plasmon resonance. Fluorescent antibodies were used to demonstrate uptake into trypanosomes in culture. Toxin-conjugated antibodies were effective at killing trypanosomes at sub-nanomolar concentrations. The approach of using antibody-drug conjugates has proven highly effective.

Keywords: antibody-drug conjugates, phage display, transferrin receptor, trypanosomes

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Authors: M. Benlebna, B. Serier, B. Bachir Bouiadjra, S. Khalkhal

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This study focuses on the mechanical behavior of a dental prosthesis subjected to dynamic loads chewing. It covers a three-dimensional analysis by the finite element method, the level of distribution of equivalent stresses induced in the bone between the implants (depending on the number of implants). The studied structure, consisting of a braced, implant and mandibular bone is subjected to dynamic loading of variable amplitude in three directions corrono-apical, mesial-distal and bucco-lingual. These efforts simulate those of mastication. We show that compared to the implantation of a single implant, implantology using two implants promotes the weakening of the bones. This weakness is all the more likely that the implants are located in close proximity to one another.

Keywords: stress, bone, dental implant, distribution, stress levels, dynamic, effort, interaction, prosthesis

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Authors: Neslihan Demirci, Serdar Durdağı

Abstract:

Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Amina Sultan, Mohamed Ghonim, Eman Oweida, Aya Abdelaziz

Abstract:

Objective: To assess the diagnostic reliability of multi-detector CT in pre and post-operative evaluation of cochlear implant candidates. Material and Methods: The study includes 40 patients (18 males and 22 females); mean age 5.6 years. They were classified into two groups: Group A (20 patients): cochlear implant device was Nucleus-22 and Group B (20 patients): the device was MED-EL. Cochlear length (CL) and cochlear height (CH) were measured pre-operatively by 128-multidetector CT. Electrode length (EL) and insertion depth angle (α) were measured post-operatively by MDCT. Results: For Group A mean CL was 9.1 mm ± 0.4 SD; mean CH was 4.1 ± 0.3 SD; mean EL was 18 ± 2.7 SD; mean α angle was 299.05 ± 37 SD. Significant statistical correlation (P < 0.05) was found between preoperative CL and post-operative EL (r²=0.6); as well as EL and α angle (r²=0.7). Group B's mean CL was 9.1 mm ± 0.3 SD; mean CH was 4.1 ± 0.4 SD; mean EL was 27 ± 2.1 SD; mean α angle was 287.6 ± 41.7 SD. Significant statistical correlation was found between CL and EL (r²= 0.6) and α angle (r²=0.5). Also, a strong correlation was found between EL and α angle (r²=0.8). Significant statistical difference was detected between the two devices as regards to the electrode length. Conclusion: Multidetector CT is a reliable tool for preoperative planning and post-operative evaluation of the outcomes of cochlear implant operations. Cochlear length is a valuable prognostic parameter for prediction of the depth of electrode array insertion which can influence criteria of device selection.

Keywords: angle of insertion (α angle), cochlear implant (CI), cochlear length (CL), Multidetector Computed Tomography (MDCT)

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Authors: Rajesh Bansal, Amit Raj Sharma, Vakil Singh

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The success and predictability of titanium implants for long durations are well established and there has been a tremendous increase in the popularity of implants among patients as well as clinicians over the last four decades. However, sometimes complications arise, which lead to the loss of the implant as well as the prosthesis. Fracture of dental implants is rare; however, at times, implants or abutment screws fracture and lead to many problems for the clinician and the patient. Possible causes of implant fracture include improper design, overload, fatigue and corrosion. Six retrieved fractured dental implants, with varying diameters and designs, were collected from time to time to examine by scanning electron microscope (SEM) to characterize fracture behavior and assess the mechanism of fracture. In this investigation, it was observed that fracture of the five dental implants occurred due to fatigue crack initiation and propagation from the thread roots.

Keywords: titanium, dental, implant, fracture, failure

Procedia PDF Downloads 43

Authors: S. Haque, M. Kanapathy, E. Bollen, I. Younis, A. Mosahebi

Abstract:

Background: Implant loss due to infection is the most devastating complication of implant-based breast reconstruction. The use of negative pressure wound therapy with instillation (NPWTi) for salvage of infected implant-based breast reconstructions has shown promising results to allow early reinsertion of a new implant as an alternative to current management of delayed reinsertion. This study compares the cost implication of NPWTi against current management of delayed reinsertion of infected breast implants. Methods: 20 cases of an infected breast implant treated with NPWTi (V.A.C. VERAFLO™ Therapy) followed by early re-insertion of a new implant were compared with 20 cases who had delayed reinsertion (non-NPWTi). Average cost per person was calculated using total operative expenses, cost of inpatient stay, cost of investigations, cost of antibiotics, and cost of outpatient visits. Results: Treatment with NPWTi allowed for earlier re-insertion of a new implant (NPWTi: 9.04 ± 2.92 days vs. non-NPWTi: 236.25 ± 123.89 days). The average cost per patient for NPWTi and non-NPWTi was £14,343.13 ± £2,786.70 and £8,920.31 ± £3,005.73 respectively. All patients treated with NPWTi had one admission and spent 11.9 ± 4.1days as an inpatient while non-NPWTi patients had 2.1 ± 0.3 admissions with total length of inpatient stay of 7.1 ± 5.8days. Patients treated with NPWTi had more surgeries (NPWTi: 3.35 ± 0.81 vs. non-NPWTi: 2.2 ± 0.41), however 3 non-NPWTi cases required flap reconstruction. Patients treated with NPWTi had fewer total outpatient visits (NPWTi: 12 ± 6 vs. non-NPWTi: 14.2 ± 6.3). Conclusion: Patients treated with NPWTi incurred higher average cost per patient, longer inpatient stay, and more procedures; however, had early re-insertion of new implants and fewer admissions and outpatient visits. A further study on patient-reported outcome is essential to compare cost against patient benefit.

Keywords: breast reconstruction, cost evaluation, infection, negative pressure wound therapy

Procedia PDF Downloads 92

Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

Abstract:

In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

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Authors: Madhav Pant, Khem N. Poudel

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Wireless power transfer is continuously becoming more powerful and compact in medical implantable devices and the wide range of applications. A rectenna is designed for wireless power transfer technique that can be applied to medical implant devices. The experiment is performed using ANSYS HFSS, a full wave electromagnetic simulation. The dipole antenna combinations operating at 2.4 GHz are used for wireless power transfer and the maximum DC voltage reception by the implant considering International Commission on Non-Ionizing Radiation Protection (ICNIRP) regulation. The power receiving dipole antenna is placed inside the cylindrical geometry having the similar properties of the human body at the frequency of 2.4 GHz. Our design can provide the power at the depth of 5 mm skin and 5mm of bone for the implant. The voltage doubler/quadrupler rectifier in ANSYS Simplorer is used to calculate the exact DC current utilized by implant inside the human body. The qualitative design and analysis of this wireless power transfer method could also be used for other biomedical implants systems such as cardiac pacemaker, insulin pump, and retinal implants.

Keywords: dipole antenna, medical implants, wireless power transfer, rectifier

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Authors: Deepika Bhaskar, Neena Wadehra, Megha Gulati, Aruna Narula, R. Vishnu, Gunjan Katyal

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With drug resistance becoming widespread in Plasmodium falciparum infections, development of the alternative drugs is the desired strategy for prevention and cure of malaria. Three drug targets were selected to screen promising drug molecules from the GSK library of around 14000 molecules. Using an in silico structure-based drug designing approach, the differences in binding energies of the substrate and inhibitor were exploited between target sites of parasite and human to design a drug molecule against Plasmodium. The docking studies have shown several promising molecules from GSK library with more effective binding as compared to the already known inhibitors for the drug targets. Though stronger interaction has been shown by several molecules as compare to reference, few molecules have shown the potential as drug candidates though in vitro studies are required to validate the results.

Keywords: plasmodium, malaria, drug targets, in silico studies

Procedia PDF Downloads 418

Authors: Danny Fraser, James Zhang

Abstract:

Aim of the study: Our study aims to identify any statistically significant evidence as it relates to PROMs for mastectomy and implant-based reconstruction to guide future surgical management. Method: The demographic, pre and post-operative treatment and implant characteristics were collected of all patients at Basildon hospital who underwent breast reconstruction from 2017-2023. We used the Breast-Q psychosocial well-being, physical well-being, and satisfaction with breasts scales. An Independent t-test was conducted for each group, and linear regression of age and implant size. Results: 69 patients were contacted, and 39 PROMs returned. The mean age of patients was 57.6. 40% had smoked before, and 40.8% had BMI>30. 29 had pre-pectoral placement, and 40 had subpectoral placement. 17 had smooth implants, and 52 textured. Sub pectoral placement was associated with higher (75.7 vs. 61.9 p=0.046) psychosocial scores than pre pectoral, and textured implants were associated with a lower physical score than the smooth surface (34.7 VS 50.2 P=0.046). On linear regression, age was positively associated (p=0.007) with psychosocial score. Conclusion: We present a large cohort of patients who underwent breast reconstruction. Understanding the PROMs of these procedures can guide clinicians, patients and policy makers to be more informed of the course of rehabilitation of these operations. Significance: We have found that from a patient perspective subpectoral implant placement was associated with a statistically significant improvement in psychosocial scores.

Keywords: breast surgery, mastectomy, breast implants, oncology

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Authors: Lei Hou, Xinli Du, Nikolaos Boulgouris

Abstract:

A cochlear implant, referred to as a CI, is a small electronic device that can provide direct electrical stimulation to the auditory nerve. During cochlear implant surgery, atraumatic electrode array insertion is considered to be a crucial step. However, during implantation, the mechanical behaviour of an electrode array inside the cochlea is not known. The behaviour of an electrode array inside of the cochlea is hardly identified by regular methods. In this study, a CI electrode array capacitive sensor system is proposed. It is able to automatically determine the array state as a result of the capacitance variations. Instead of applying sensors to the electrode array, the capacitance information from the electrodes will be gathered and analysed. Results reveal that this sensing method is capable of recognising different states when fed into a pre-shaped model.

Keywords: cochlear implant, electrode, hearing preservation, insertion force, capacitive sensing

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Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

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Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

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