Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends.

The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed.

Laboratory Safety Climate Assessment and its Correlation with Safety Procedures Amongst Staff of a Reference Clinical Laboratory.

OBJECTIVE: To compare and correlate safety climate standards and safety practices among different subspecialities of pathology. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: The study was conducted at Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from February to November 2022. METHODOLOGY: Responses of 199 participants were recorded according to the validated Nordic Safety Climate Questionnaire (NOSACQ-50) and Lab Safety Survey form. The safety climate presented as seven dimensions according to the validated questionnaire was compared among different workgroups, based on subspeciality and job designation, using one-way ANOVA and independent sample t-test, respectively. Pearson's correlation was used to assess the relationship between the safety climate and safety practices. RESULTS: Among the safety climate dimensions, safety communication, trust in co-workers' safety competence (M=3.02) and workers trust in efficacy of safety systems (M=3.00) were the most positively perceived aspects followed by management's safety priority (M=2.98). Comparison of subspecialities showed significant differences in management safety empowerment, management safety justice, workers' safety commitment, safety communication, and trust in efficiency of safety systems (p<0.001 for all 5 factors). Chemical pathology workers and technical staff were workgroups with lower safety climate scores. A statistically significant positive correlation (r=0.97) was observed between the safety procedures and safety climate at an organisational level. CONCLUSION: The results demonstrated the existence of a good safety climate within the participating laboratories of the institute. It successfully identified areas that need further safety improvements. The study will help increase awareness about occupational safety and safety culture among healthcare workers in general and clinical laboratory setups in particular. KEY WORDS: Laboratory safety climate, Occupational health, Safe laboratory practices.

The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats.

Citronellol has been reported to have anti-inflammatory, anti-cancer, and antihypertensive activities, but its effect on myocardial ischemia is still unclear. The aim of this study was to investigate the therapeutic effects and pharmacological mechanisms of citronellol on ischemia. Therefore, a rat model of myocardial ischemia was established using the doxorubicin (DOX) model. To induce cardiotoxicity, the rats were given DOX (2.5 mg/kg) intraperitoneally over a 14-day period. Group I served as the control and received tween 80 (0.2%), group II received the vehicle and DOX, group III received the standard drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX, respectively. After treatment, the rats were euthanized, and blood samples were collected to assess the levels of serum cardiac markers, lipid profiles, and tissue antioxidant enzymes. The gene expressions of eNOS, PPAR-g, IL-10, VEGF, and NFkB-1 were also determined using real-time polymerase chain reactions. Simultaneous treatment with DOX and citronellol reduced cardiac antioxidant enzymes and lipid biomarkers in a dose-dependent manner. Citronellol also increased the expression of anti-inflammatory cytokines while reducing the expression of pro-inflammatory cytokines. Therefore, it can be concluded that citronellol may have potential cardioprotective effects in preventing DOX-induced cardiotoxicity.

Fifth Generation Quality Control of Immunoassay Parameters by Six Sigma Value.

OBJECTIVE: To determine the sigma value of immunoassay parameters which are within the 2Z score on external quality control (EQC). STUDY DESIGN: A cross-sectional study. Place and Duration of the Study: Department of Chemical Pathology and Endocrinology (AFIP),non-ability ity consecutive  from June to November 2022. METHODOLOGY: Ten immunoassay parameters were selected on the basis of the internal quality control (IQC) and external quality control (EQC) programs. The Clinical Laboratory Improvement Amendments (CLIA) is used for Total Allowable Error (TEa). Sigma value was calculated from coefficient of variation (CV) and bias, which was determined by IQC and EQC, observed for 6 subsequent months. If the sigma values are ≥6, between 3 and 5, and <3, they are classified as good, acceptable or unacceptable, respectively. RESULTS: T4, prolactin, Vitamin B12 at >3 ó at IQC level 1. TSH, T3, T4, and Vitamin B12 showed that on level 2 IQC at >3 ó T3, Vitamin D at 4-5 ó level, Prolactin, FSH, and LH at 6 ó level in level 2 IQC. In the EQC program, the sigma level calculated for ten assays found that almost all parameters were at sigma >3 ó level except TSH which was at 5.8 Ï­ level during June to August 2022. From September to November 2022, all parameters at >3 ó level except for TSH, growth hormone, FSH, LH, and Vitamin b12 which showed at 4.4 ó level. CONCLUSION: Most of the immunoassay parameters show good performance in the EQC program and at both levels of IQC level with sigma value 4-5. KEY WORDS: Bias, Six sigma, Key performance indicators, External quality control.

Biological Role of Zinc in Liver Cirrhosis: An Updated Review.

Liver cirrhosis is a complication usually due to the consequence of persistent chronic liver disease. It is associated with different mechanisms, including hypoalbuminemia, impaired amino acid turnover, and micronutrient deficiencies. Consequently, cirrhotic patients can develop progressive complications like ascites, hepatic encephalopathy, and hepatocellular carcinoma. The liver is a vital organ that regulates the different metabolic pathways and transportation of trace elements. Zn is an indispensable micronutrient trace element involved in its crucial functions in cellular metabolic activity. Zn mediates its action by binding to a wide range of proteins; therefore, it imparts numerous biological effects, including cellular division, differentiation, and growth. It is also involved in critical processes for the biosynthesis of structural proteins and regulation of transcription factors and acts as a co-factor for the various enzymatic processes. As the liver is a significant regulator of Zn metabolism, its abnormalities lead to Zn deficiency, which has consequences on cellular, endocrine, immune, sensory, and skin dysfunctions. Conversely, Zn deficiency may modify the functions of hepatocytes and immune responses (acute phase protein production) in inflammatory liver diseases. This review has concisely stated the evolving indication of the critical role of Zn in biological processes and complications associated with liver cirrhosis pathogenesis due to Zn deficiency.

Correlation of Serum Erythropoietin Levels with Different Stages of Diabetic Retinopathy.

OBJECTIVE: To determine the correlation of serum erythropoietin concentration with diabetic retinopathy in patients with type 2 diabetes mellitus. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July to December 2021. METHODOLOGY: A total of 180 individuals were enrolled in the study and placed in 2 groups as group 1 have 90 cases of type 2 diabetes mellitus and group 2 having 90 age-matched healthy controls. Group 1 was further subclassified into proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR) subgroups by an expert ophthalmologist. Serum erythropoietin, creatinine, blood HbA1c, and haemoglobin were analysed. Correlation between stages of proliferation and serum erythropoietin, creatinine, blood HbA1c, and haemoglobin were analysed. An independent-sample student t-test was applied to compare mean Serum erythropoietin between PDR and NPDR groups. Pearson's correlation was applied among disease severity, and type of retinopathy. A p-value of ≤0.05 was considered significant. RESULTS: The average age of participants in groups 1 and 2 was 45.88±8.6 and 56.6±10.23 years, respectively. More males (n=60, 66.7%) were noted in cases compared to controls (n=42, 46.7%). serum erythropoietin concentration observed in cases (8.4±1.87 IU/L) was higher than controls (6.50±0.9). The mean serum erythropoietin concentration in PDR (9.35±1.74 IU/L) was significantly greater than that in NPDR (7.3±1.38 IU/L, p <0.001). The serum concentration of erythropoietin in group 1 increased linearly with the severity of the disease (r=0.103). CONCLUSION: Serum erythropoietin concentrations increased in uncontrolled type 2 diabetics more so in proliferative retinopathy cases, and increased with disease severity. KEY WORDS: Erythropoietin, Diabetic retinopathy, Proliferative diabetic retinopathy.

Development of Carbon-Nanodot-Loaded PLA Nanofibers and Study of Their Barrier Performance for Medical Applications.

The COVID-19 pandemic has increased the usage of personal protective equipment (PPE) all round the world and, in turn, it has also increased the waste caused by disposable PPE. This has exerted a severe environmental impact, so in our work, we propose the utilization of a sustainable electrospun nanofiber based on poly lactic acid (PLA), as it is biobased and conditionally degradable. We optimized the weight percentage of the PLA-precursor solution and found that 19% PLA produces fine nanofibers with good morphology. We also introduced carbon nanodots (CNDs) in the nanofibers and evaluated their antibacterial efficiency. We used 1, 2, 3, and 4% CNDs with 19% PLA and found increased antibacterial activity with increased concentrations of CNDs. Additionally, we also applied a spunbond-nanofiber layered assembly for the medical face masks and found that with the addition of only 0.45 mg/cm2 on the nonwoven sheet, excellent particle filtration efficiency of 96.5% and a differential pressure of 39 Pa/cm2 were achieved, meeting the basic requirements for Type I medical face masks (ASTM-F2100).

Evaluation of hypomagnesaemia in diabetic patients with nephropathy in a reference clinical laboratory: A comparative cross sectional study.

Serum Magnesium plays a significant role in different diabetic complications. This comparative cross sectional study was conducted to evaluate serum magnesium levels in patients with Type 2 Diabetes Mellitus (T2DM) with and without nephropathy. A total of 182 diabetic patients (91 with nephropathy and 91 without nephropathy) were included. Odds ratio were calculated and Mann Whitney U test was used to compare quantitative variables; p<0.05 was considered significant. The results showed that 64/91 (70.3%) patients with nephropathy had hypomagnesaemia as compared to 21/91 (23.07%) patients without nephropathy. The risk of hypomagnesaemia was higher in patients with nephropathy than without nephropathy (Odds ratio 2.7 vs 0.34). Median magnesium levels (1.73 mg/dl) were lower in patients with nephropathy as compared to patients without nephropathy (2.09 mg/dl), p<0.01. It is concluded that magnesium levels were significantly lower in patients with diabetic nephropathy as compared to without nephropathy.

Advanced and Smart Textiles during and after the COVID-19 Pandemic: Issues, Challenges, and Innovations.

The COVID-19 pandemic has hugely affected the textile and apparel industry. Besides the negative impact due to supply chain disruptions, drop in demand, liquidity problems, and overstocking, this pandemic was found to be a window of opportunity since it accelerated the ongoing digitalization trends and the use of functional materials in the textile industry. This review paper covers the development of smart and advanced textiles that emerged as a response to the outbreak of SARS-CoV-2. We extensively cover the advancements in developing smart textiles that enable monitoring and sensing through electrospun nanofibers and nanogenerators. Additionally, we focus on improving medical textiles mainly through enhanced antiviral capabilities, which play a crucial role in pandemic prevention, protection, and control. We summarize the challenges that arise from personal protective equipment (PPE) disposal and finally give an overview of new smart textile-based products that emerged in the markets related to the control and spread reduction of SARS-CoV-2.

Emerging role of macrophages in non-infectious diseases: An update.

In the past three decades, a huge body of evidence through various research studies conducted on animal models, has demonstrated that the macrophages are centralized of all the leukocytes involved in diseases and, particularly, their role in non-infectious diseases has been studied extensively for which they have also been referred to as the "double-edged swords". The most versatile of all immunocytes, macrophages play a key role in health and diseases. Various experimental models have demonstrated the conventional paradigms such as the M1/M2 dichotomy, which is not as obvious and presents a complex characterization of the macrophages in the disease immunology. In human diseases, this M1-M2 continuum shows a complex web of mechanisms, which are majorly divided into the pro-inflammatory roles (derived mainly by the cytokines: IL-1, IL-6, IL-12, IL-23, and tumor necrosis factor) and anti-inflammatory roles (CCl-17, CCl-22, CCL-2, transforming growth factor (TGF), and interleukin-10), which are involved in the wound healing and pathogen-suppression. The conventional division of these macrophages as M1 and M2 is derived from the opposing functions of these macrophages; where M1 is involved in the tissue damage and pro-inflammatory roles and M2 promotes cell proliferation and the resolution of inflammation. Both these pathways down-regulate each other in diseases through a plethora of enzymatic and cytokine mediators.

Discovery of Novel Tetramethylpyrazine Containing Chalcone Derivatives as Anti-Inflammatory Agents.

BACKGROUND: Chalcones are precursors of flavonoids and exhibit a broad spectrum of pharmacological activity. OBJECTIVE: As anti-inflammatory agents, two series of chalcone derivatives and chalcone-based oximes were synthesized and characterized. To integrate the tetramethylpyrazine moiety into these novel molecules, the multifunctional natural chemical ligustrazine was employed. METHODS: A variety of newly synthesized ligustrazine-based chalcones were utilized as precursors for the synthesis of new oximes and their inhibitory activity against COX-1, COX-2, and LOX-5 enzymes were compared. RESULTS: The conversion of ketones to their oxime derivatives increased the effectiveness of COX-1 and COX-2 inhibition. Due to the substituted ether groups, oxime derivative 5d had the lowest IC50 values of 0.027 ± 0.004 µM and 0.150 ± 0.027 µM for COX-1 and COX-2 isoenzymes, respectively. Notably, the oxime derivative's highest effectiveness is conferred by the presence of methoxymethoxy or hydroxy groups at the C-3 and C-4 positions on the phenyl ring. The 6b derivative with a long alkyl chain ether group was shown to be the most powerful 5-LOX inhibitor. All compounds were also assessed for their ability to inhibit nitric oxide generation and LPS-induced IL-6, IL-1ß, and TNF-α production in RAW 264.7 macrophages. Finally, in order to determine the structural effects responsible for the binding mechanism of compounds, they were docked into the binding sites of COX-1, COX-2, and 5-LOX, which revealed an inhibitory mechanism of action and demonstrated the relevance of various types of interactions. CONCLUSION: The findings showed that these novel compounds had a significant impact on antiinflammatory actions.

In Vitro and In Vivo Evaluation of Hydroxypropyl-ß-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) Semi-Interpenetrating Matrices of Dexamethasone Sodium Phosphate.

In this paper, we fabricated semi-interpenetrating polymeric network (semi-IPN) of hydroxypropyl-ß-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) (HP-ß-CD-g-poly(AA)/PVP) by the free radical polymerization technique, intended for colon specific release of dexamethasone sodium phosphate (DSP). Different proportions of polyvinyl pyrrolidone (PVP), acrylic acid (AA), and hydroxypropyl-beta-cyclodextrin (HP-ß-CD) were reacted along with ammonium persulphate (APS) as initiator and methylene-bis-acrylamide (MBA) as crosslinker to develop a hydrogel system with optimum swelling at distal intestinal pH. Initially, all formulations were screened for swelling behavior and AP-8 was chosen as optimum formulation. This formulation was capable of releasing a small amount of drug at acidic pH (1.2), while a maximum amount of drug was released at colonic pH (7.4) by the non-Fickian diffusion mechanism. Fourier transformed infrared spectroscopy (FTIR) revealed successful grafting of components and development of semi-IPN structure without any interaction with DSP. Thermogravimetric analysis (TGA) confirmed the thermal stability of developed semi-IPN. X-ray diffraction (XRD) revealed reduction in crystallinity of DSP upon loading in the hydrogel. The scanning electron microscopic (SEM) images revealed a rough and porous hydrogel surface. The toxicological evaluation of semi-IPN hydrogels confirmed their bio-safety and hemocompatibility. Therefore, the prepared hydrogels were pH sensitive, biocompatible, showed good swelling, mechanical properties, and were efficient in releasing the drug in the colonic environment. Therefore, AP-8 can be deemed as a potential carrier for targeted delivery of DSP to treat inflammatory bowel diseases.

Fabrication, In Vitro and In Vivo Evaluation of Non-Ordered Mesoporous Silica-Based Ternary Solid Dispersions for Enhanced Solubility of Flurbiprofen.

The aim of this study was to improve the solubility and prevent the ulcerogenic effect of flurbiprofen. Initially, binary and ternary solid dispersions (BSDs and TSDs) of flurbiprofen were prepared by using non-ordered mesoporous silica and gelucire. After preformulation testing (solubility, flow properties, % yield, and entrapment efficiency), four formulations were selected for further detailed studies. Solid-state characterization of optimized formulations (S1, S6, S7, and S12) showed successful drug incorporation in the solid dispersion at the molecular state without any noticeable interactions. The in vitro solubility and release study showed an increase in solubility and 98-100% of drug release in 30-45 min. The in vivo gastro-protective effect of the optimized formulations containing flurbiprofen and silica (1:1) with 25% w/w gelucire (S6 and S12) showed a reduction in the gastric lesion index (GLI) after four days of treatment. Moreover, histological images of the stomach lining (S6 and S12) illustrated normal epithelial cells and a partially protected mucosal membrane. Thus, TSD exhibited a significant increase in solubility and the dissolution rate and reduced the gastric ulceration. Therefore, TSDs are dubbed as efficacious carriers to enhance the bioavailability of flurbiprofen while simultaneously reducing its side effects.

Assessing the Synergistic Activity of Clarithromycin and Therapeutic Oils Encapsulated in Sodium Alginate Based Floating Microbeads.

We developed alginate-based floating microbeads of clarithromycin with therapeutic oils for the possible eradication of Helicobacter pylori (H. pylori) infections by enhancing the residence time of the carrier at the site of infection. In pursuit of this endeavor, the alginate was blended with hydroxy propyl methyl cellulose (HPMC) as an interpenetrating polymer to develop beads by ionotropic gelation using calcium carbonate as a gas generating agent. The developed microbeads remained buoyant under gastric conditions for 24 h. These microbeads initially swelled and afterwards decreased in size, possibly due to the erosion of the polymer. Furthermore, swelling was also affected by the type of encapsulated oil, i.e., swelling decreased with increasing concentrations of eucalyptus oil and increased with increasing concentrations of oleic acid. Antibacterial assays of the formulations showed significant antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli); these assays also showed synergistic activity between clarithromycin and therapeutic oils as evident from the higher zone of inhibition of the microbeads as compared to the pure drug and oils. Scanning electron microscopy (SEM) images revealed a smoother surface for oleic acid containing the formulation as compared to eucalyptus oil containing the formulation. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed the development of a stable formulation, while Fourier transform infrared spectrophotometry (FTIR) studies did not reveal any interaction between the polymers and the active ingredients. Optimized formulations (CLM3 and CLM6) were designed to release the drug in a controlled manner in gastric media by Fickian diffusion. Conclusively, the developed microbeads are a promising carrier to overcome the narrow therapeutic index and low bioavailability of clarithromycin, while the presence of therapeutic oils will produce synergistic effects with the drug to eradicate infection effectively.

Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties.

A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds 4h, 4j and 5d. Being the most potent, compound 4h showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound 4h was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound 4h induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound 4h was lodged on nanostructured lipid carriers (NLCs). 23 full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC50 by around 2.15 times for pure 4h, while nearly close to the IC50 of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity.

Nanomedicine Penetration to Tumor: Challenges, and Advanced Strategies to Tackle This Issue.

Nanomedicine has been under investigation for several years to improve the efficiency of chemotherapeutics, having minimal pharmacological effects clinically. Ineffective tumor penetration is mediated by tumor environments, including limited vascular system, rising cancer cells, higher interstitial pressure, and extra-cellular matrix, among other things. Thus far, numerous methods to increase nanomedicine access to tumors have been described, including the manipulation of tumor micro-environments and the improvement of nanomedicine characteristics; however, such outdated approaches still have shortcomings. Multi-functional convertible nanocarriers have recently been developed as an innovative nanomedicine generation with excellent tumor infiltration abilities, such as tumor-penetrating peptide-mediated transcellular transport. The developments and limitations of nanomedicines, as well as expectations for better outcomes of tumor penetration, are discussed in this review.

A case of congenital methaemoglobinaemia with secondary polycythemia.

Haemoglobin contains iron in a ferrous form. When the iron is oxidized, it is called Methaemoglobin (MetHb). MetHb leads to tissue hypoxia, cyanosis, and secondary polycythemia. Methaemoglobinaemia is acquired or congenital. In this case, a 22-years-old male patient presented with cyanosis, headache, and lack of concentration. Cyanosis was present since birth. His previous investigations showed polycythemia. He was misdiagnosed on multiple occasions and was undergoing venesections for polycythemia. On evaluation at a private clinic, an Oxygen saturation gap was noted between the results of the pulse oximeter and arterial blood gas analyzer. This raised suspicion on the presence of MetHb. He was referred to Armed Forces Institute of Pathology, Rawalpindi for further workup.The sample obtained for MetHb was chocolate brown in colour. Analysis was done via co-oximetry. A high level of MetHb (45.6%) was obtained. All other radiological and haematological investigations were in the normal range. On the basis of history, clinical presentation, and investigations, he was diagnosed as a case of congenital methaemoglobinaemia with secondary polycythemia.

Synthesis, Characterization, Functionalization and Bio-Applications of Hydroxyapatite Nanomaterials: An Overview.

Hydroxyapatite (HA) is similar to natural bone regarding composition, and its structure favors in biomedical applications. Continuous research and progress on HA nanomaterials (HA-NMs) have explored novel fabrication approaches coupled with functionalization and characterization methods. These nanomaterials have a significant role in many biomedical areas like sustained drug and gene delivery, bio-imaging, magnetic resonance, cell separation, and hyperthermia treatment due to their promising biocompatibility. This review highlighted the HA-NMs chemical composition, recent progress in synthesis methods, characterization and surface modification methods, ion-doping, and role in biomedical applications. HA-NMs have a substantial role as drug delivery vehicles, coating material, bone implant, coating, ceramic, and composite materials. Here, we try to summarize an overview of HA-NMs with the provision of future directions.

Synthesis and Characterization of Antibiotic-Loaded Biodegradable Citrate Functionalized Mesoporous Hydroxyapatite Nanocarriers as an Alternative Treatment for Bone Infections.

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to provide an alternative to currently available bone-infection treatments. Here we designed mesoporous hydroxyapatite nanocarriers functionalized with citrate (Ctr-mpHANCs). Amoxicillin (AMX) is used as a model drug to load in Ctr-mpHANCs, and the drug loading was more than 90% due to the porous nature of nanocarriers. Scanning electron microscopy shows the roughly spherical morphology of nanocarriers, and the DLS study showed the approximate size of 92 nm. The Brunauer-Emmett-Teller (BET) specific surface area and pore diameter was found to be about 182.35 m2/g and 4.2 nm, respectively. We noticed that almost 100% of the drug is released from the AMX loaded Ctr-mpHANCs (AMX@Ctr-mpHANCs) in a pH-dependent manner within 3 d and 5 d at pH 2.0 and 4.5, respectively. The sustained drug release behaviour was observed for 15 d at pH 7.4 and no RBCs hemolysis by AMX@Ctr-mpHANCs. The broth dilution and colony forming unit (CFU) assays were used to determine the antimicrobial potential of AMX@Ctr-mpHANCs. It was observed in both studies that AMX@Ctr-mpHANCs showed a significant reduction in the bacterial growth of S. aureus, E. coli, and P. aeruginosa as compared to Ctr-mpHANCs with no bacteria-killing. Thus, we proposed that Ctr-mpHANCs can be used as a drug carrier and a treatment option for bone infections caused by bacteria.

Metal Complexation of Arabinoxylan Engenders a Smart Material Offering pH, Solvents, and Salt Responsive On-Off Swelling with the Potential for Sustained Drug Delivery.

The present study aimed to develop a stable interconnected matrix as a sustained release drug delivery material. Arabinoxylan (AX) was extracted from ispaghula husk and then crosslinked with different concentrations, i.e., 0.5, 1.0, and 1.5 g of CaCl2 per 0.25 g of AX. The crosslinking was confirmed through Fourier transform infrared spectroscopy. The swelling capacity of crosslinked AX (CL-AX) was evaluated against buffer solutions of pH 1.2, 6.8, 7.4, and water. The swelling capacity increased from pH 1.2 to pH 7.4 and followed the second order swelling kinetics. The swelling study also revealed that CL-AX with 1.0 g CaCl2 showed maximum swelling capacity. The swelling-deswelling (on-off switching) behavior of CL-AX was evaluated in water-ethanol, water-0.9% NaCl solution, and buffer solutions of pH 7.4-1.2 and showed responsive swelling-deswelling behavior. Scanning electron microscopy revealed a highly porous nature of CL-AX with a mesh of thin fibrous networking. Hemocompatibility studies of CL-AX revealed its non-thrombogenic and nonhemolytic attributes. The CL-AX matrix tablet prolonged the release of enalapril maleate for 24 h, and the drug release followed the zero order kinetics and super case-II transport mechanism. Therefore, CL-AX can be recognized as a stimuli responsive and hemocompatible biomaterial with sustained drug release potential.