A randomized, double-blind, positive-controlled, Phase-II clinical trial to evaluate efficacy and safety of Fuke Qianjin capsule in Pakistani patients with pelvic inflammatory disease.

Ethnopharmacological relevance: Pelvic inflammatory disease (PID) is a frequently occurring gynecological disorder mainly caused by the inflammation of a woman's upper genital tract. Generally, antibiotics are used for treating PID, but prolonged use poses potential risks of gut bacterial imbalance, bacterial resistance, super bacteria production, and associated adverse reactions. Traditional Chinese medicine (TCM) has shown unique advantages in various ailments and has received widespread clinical research attention. Fuke Qianjin (FUKE) capsule is an approved National Medical Products Administration (NMPA License No. Z20020024) Chinese herbal prescription that has been widely used individually or in combination with other Western medicines for the treatment of various gynecological inflammatory diseases, including chronic cervicitis, endometritis, and chronic PID. Aim: This clinical trial was designed to assess the safety and efficacy of FUKE capsule in mild-to-moderate symptomatic PID patients. Materials and methods: This phase 2, randomized, double-blind, positive controlled clinical trial was conducted in mild-to-moderate symptomatic PID patients at a single center in Pakistan from 21 September 2021 to 11 March 2022. Eligible female participants were randomly assigned to a test and a control group with a ratio of 1:1. The test group subjects received two metronidazole (METRO) tablets and one doxycycline hyclate (DOXY) simulant at a time, twice daily for 14 days, and two Fuke Qianjin (FUKE) capsules, three times a day after a meal for 28 days. Subjects in the control group received two METRO tablets and one DOXY tablet at a time, twice daily for 14 days, and two FUKE simulant capsules, three times a day after meal for 28 days. The primary efficacy outcome was an improvement in pelvic pain symptoms assessed through a visual analog scale (VAS). The secondary outcomes were the improvement in secondary efficacy symptoms like local physical signs, clinical assessment of leucorrhea and cervical secretions through laboratory examination, and improvement in the maximum area of pelvic effusion assessed through gynecological ultrasound after the treatment. The safety outcomes were assessed through vital signs, laboratory tests, electrocardiogram findings, and adverse events/serious adverse events. Results: A total of 198 subjects with active PID were randomly assigned to a test group (n = 99) and a control group (n = 99). The baseline characteristics of the subjects in the two groups were similar. In the intention-to-treat analysis, the primary efficacy was 84.9% for the test group and 71.6% for the control group, with a statistically significant difference (p = 0.0370; 95% CI -0.2568 to -0.0088). The secondary clinical efficacy was 88.4% for the test group and 82.7% for the control group, with no significant difference (p = 0.2977; 95% CI -0.1632 to 0.0501). The improvement in local physical signs was 95.8% for the test group and 76.9% for the control group, with no significant difference (p = 0.0542; 95% CI -0.3697 to -0.0085). The inter-group non-inferiority comparison showed that the upper limit of the 95% CI was less than 0.15 and thus met the non-inferiority requirements of the test group to the control group. The results of clinical signs of leucorrhea and cervical secretions showed that there was no difference in the rate of improvement between the test and control groups, indicating that FUKE was non-inferior to DOXY. A total of 14 adverse events in eight subjects were observed in the trial, with an incidence rate of 4.7%. Four subjects in each group experienced seven adverse events with 4.5% and 4.8% incidence rates of adverse reactions in the test and control groups, with no statistically significant differences (p = 0.2001). No serious adverse events occurred in the trial. Conclusion: The results of this trial indicate that the test drug (Fuke Qianjin capsule) is non-inferior to the control drug (doxycycline hyclate tablet) in treating mild-to-moderate PID patients with comparable efficacy, safety, and tolerability to the control drug. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT04723069.

Smartphone-assimilated colorimetric sensor for sub-nanomolar emamectin detection via KA30 capped silver nanoparticles in food, bio-fluids and water samples.

In this report, we firstly synthesized nitro calix [4] resorcinarene compound (referred as KA30) and characterized it though proton (1H) nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and Fourier Transform Infra-red (FTIR) spectroscopy. KA30 was applied as functionalizing agent for the formation of silver nanoparticles (KA30-AgNPs). These NPs were confirmed as highly selective and extremely sensitive colorimetric sensor for ultra-low level detection of emamectin (EMA) as a novel report. Significant aspect of the sensor is its unique detection range between 0.0005 and 29.5 µM via color change from yellow to colorless with hypochromic-bathochromic shift exhibiting limit of detection (LOD) and limit of quantification (LOQ) as 0.12 nM and 0.4 nM respectively. The sensor was applied to colorimetrically and optically detect EMA in real samples of serum, urine and food. The sensor was further allied with smartphone for real-time, and on-site detection of EMA and results were validated through UPLC.

Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation.

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.

The safety and efficacy of Houtou Jianweiling tablet in patients with chronic non-atrophic gastritis: a double-blind, non-inferiority, randomized controlled trial.

Background: Common symptoms of Chronic Non-atrophic Gastritis (CNAG) include nausea, stomach distension, and abdominal pain. The Houtou Jianweiling Tablet (HTJWT) is a chinese patent medicine (CN1368229A) and it has been used clinically for more than 20 years with proven clinical efficacy in treating CNAG, prompted us to establish the clinical efficacy and safety of HTJWT on patients with mild to moderate CNAG symptoms in Pakistani population. Methods: This phase II, double-blind, randomized, parallel-controlled trial was conducted in a single center between November 2022 and February 2023 in Pakistan. In a ratio of 1:1, total 240 CNAG patients with erosion identified by pathological biopsy and gastroscopy were randomly assigned to control (Omeprazole) group (n = 120) and the treatment (HTJWT) group (n = 120). Patients in the treatment group received orally four HTJWT (0.38g/tablet), three times a day and one placebo of Omeprazole enteric-coated tablet prior to breakfast, daily. On the other hand, patients in the control group received one Omeprazole enteric-coated tablet (20 mg/tablet) prior to breakfast and four placebo of HTJWT, thrice a day. The patients consumed the investigated drugs (i.e., treatment and control) treatment regimen was followed for a duration of 28 days. The safety of the patients were evaluated through adverse events, serious adverse events and laboratory tests such as blood biochemistry, urine analysis, liver and renal function tests. Vital signs like; blood pressure, pulse rate, body temperature, respiratory rate for all the patients were recorded. The cardiac status of the patients were assessed through electrocardiogram (ECG). The primary efficacy indicators were the improvement rate of gastric distention and gastralgia as the main clinical symptoms. Secondary indicators were visual analogue score (VAS); improvement rate of secondary clinical symptoms and signs; improvement rate of total clinical signs and symptoms; the disappearance/remission rate of Gastric pain and, remission/disappearance time of gastric distension; and the negative conversion rate of Helicobacter pylori (H. pylori). The outcomes among each group were compared using the chi-square test. Results: Patients in both groups had good drug compliance (80%-120%), and there was no statistically significant difference in the patients' baseline characteristics. The clinical improvement rate was found to be 91.1% in the treatment group and 91.0% in the control group with negligible variation among the two groups (p = 0.9824; 95% confidence interval: -0.0781-0.0798). Similarly, hardly no difference was found in the negative conversion rate of H. pylori between the treatment group and the control group (i.e., 70.1% and 71.8% respectively, p = 0.8125). There were no significant differences in respiratory rate, vital signs, blood pressure, laboratory results for blood biochemistry, urine analysis, liver and renal function tests between the two groups. The ECG assessment carried out for the treatment and control group revealed no considerable difference. Margin variation in the disappearance time of gastric pain (p = 0.1860) and remission rate (p = 0.5784) between the two groups were observed. The control group exhibited a faster remission period for gastrointestinal discomfort indications as compared to treatment group (p = 0.0430). Only one patient in the control group experienced mild to moderate adverse events, namely,; epigastric pain and dyspepsia. The results were consistent with the intention-to-treat and per-protocol analysis that included patients who were 100% compliant to the assigned therapy. Conclusion: The lower limit of confidence interval (CI, 95%) for the differences in the effective rate between the treatment and the control groups was found to be -0.0781 which is greater than -0.15, hence the treatment group is non-inferior to the control group. The therapeutic dosage used in the trial and treatment period did not cause any significant adverse event, and there were no obvious changes in the ECG profile, vital signs and biochemistry of the patients. Based on the clinical efficacy evaluation and reported adverse events, it can be concluded that the HTJWT is a safe and effective traditional chinese medicine for the treatment of patients suffering from chronic non-atrophic gastritis with mild to moderate symptoms. Clinical Trial Registration: [www.clinicaltrials.gov], identifier [NCT04672018].

Antibacterial effects of quercetagetin are significantly enhanced upon conjugation with chitosan engineered copper oxide nanoparticles.

The development of antibiotic alternatives that entail distinctive chemistry and modes of action is necessary due to the threat posed by drug resistance. Nanotechnology has gained increasing attention in recent years, as a vehicle to enhance the efficacy of existing antimicrobials. In this study, Chitosan copper oxide nanoparticles (CHI-CuO) were synthesized and were further loaded with Quercetagetin (QTG) to achieve the desired (CHI-CuO-QTG). Size distribution, zeta potential and morphological analysis were accomplished. Next, the developed CHI-CuO-QTG was assessed for synergistic antibacterial properties, as well as cytotoxic attributes. Bactericidal assays revealed that CHI-CuO conjugation showed remarkable effects and enhanced QTG effects against a range of Gram + ve and Gram - ve bacteria. The MIC50 of QTG against S. pyogenes was 107 µg/mL while CHI-CuO-QTG reduced it to 9 µg/mL. Similar results were observed when tested against S. pneumoniae. Likewise, the MIC50 of QTG against S. enterica was 38 µg/mL while CHI-CuO-QTG reduced it to 7 µg/mL. For E. coli K1, the MIC50 of QTG was 42 µg/mL while with CHI-CuO-QTG it was 23 µg/mL. Finally, the MIC50 of QTG against S. marcescens was 98 µg/mL while CHI-CuO-QTG reduced it to 10 µg/mL. Notably, the CHI-CuO-QTG nano-formulation showed limited damage when tested against human cells using lactate dehydrogenase release assays. Importantly, bacterial-mediated human cell damage was reduced by prior treatment of bacteria using drug nano-formulations. These findings are remarkable and clearly demonstrate that drug-nanoparticle formulations using nanotechnology is an important avenue in developing potential therapeutic interventions against microbial infections.

Bioequivalence assessment of two Ticagrelor formulations under fasting condition in healthy Pakistani subjects.

Objective: To investigate the Bioequivalence of Anplag® 90mg (Ticagrelor) tablet and Brilinta® 90 mg (Ticagrelor) tablet under fasting conditions in healthy Pakistani subjects. Method: This was an open-label, cross-over, randomized, single-dose, two-period, single-center Bioequivalence Study conducted at Center of Bioequivalence Studies and Clinical Research (CBSCR), ICCBS, University of Karachi, Karachi, Pakistan from September 2020 to January 2021. This was an open-label, randomized, single-dose, two-period, cross-over Bioequivalence Study. After randomization, a single dose of Ticagrelor 90mg tablet (test or reference drug) were administered orally in 1:1 ratio to each subject under fasting conditions. Seven days washout period was kept between the two periods in order to avoid carry over. Blood samples were then taken up to 48th hours post-dose. Point estimates and 90% confidence intervals (CI) for the ratio of the log-transformed values were calculated. Bioequivalence assessment of both, the reference and the test drugs were based on the primary Pharmacokinetic PK metrics including peak maximum concentration (Cmax), area under the curve (AUC) from zero to last quantifiable concentration (AUClast), and AUC from zero to infinity (AUCtotal) after log-transformation of data with ANOVA. In this bioequivalence study, the primary pharmacokinetic parameters were assessed for both Ticagrelor and its Active Metabolite (AR-C124910XX). Safety endpoints were evaluated by monitoring adverse events (AEs). Results: The 90% Confidence Intervals (CIs) of the Geometric Mean Ratio for primary PK parameters including Cmax, AUClast, and AUCtotal all were within the accepted bioequivalence range of 80%- 125%. In the current study, no serious adverse events were reported. Conclusion: Our results showed that the two tested formulations of Ticagrelor tablets were bioequivalent and well tolerated.Trial Registration: ClinicalTrials.gov Identifier: NCT04941196.

Boosting photo-induced antimicrobial activity of lignin nanoparticles with curcumin and zinc oxide.

Lignin nanoparticles have gained increasing attention as a potential antimicrobial agent due to their biocompatibility, biodegradability, and low toxicity. However, the limited ability of lignin to act as an antibacterial is a major barrier to its widespread use. Thus, it is crucial to develop novel approaches to amplify lignin's biological capabilities in order to promote its effective utilization. In this study, we modified lignin nanoparticles (LNPs) with photo-active curcumin (Cur), zinc oxide (ZnO), or a combination of both to enhance their antimicrobial properties. The successful modifications of LNPs were confirmed using comprehensive characterization techniques. The antimicrobial efficacy of the modified LNPs was assessed against both gram-positive and gram-negative bacterial strains. The results showed that the modification of LNPs with Cur and ZnO have much higher antibacterial and antibiofilm activities than unmodified LNPs. Moreover, photo illumination resulted in even higher antibacterial activity. Furthermore, atomic force microscopy revealed bacterial cells lysis and membrane damage by ZnO/Cur modified LNPs. Our research demonstrates that ZnO/Cur modified LNPs can serve as novel hybrid materials with enhanced antimicrobial capabilities. In addition, the photo-induced enhancement in antibacterial activity not only demonstrated the versatility of this hybrid material but also opened up interesting potential for bioinspired therapeutics agents.

Microarray needles comprised of arginine-modified chitosan/PVA hydrogel for enhanced antibacterial and wound healing potential of curcumin.

Wound healing is a multifaceted and complex process that includes inflammation, hemostasis, remodeling, and granulation. Failures in any link may cause the healing process to be delayed. As a result, wound healing has always been a main research focus across the entire medical field, posing significant challenges and financial burdens. Hence, the current investigation focused on the design and development of arginine-modified chitosan/PVA hydrogel-based microneedles (MNs) as a curcumin (CUR) delivery system for improved wound healing and antibacterial activity. The substrate possesses exceptional swelling capabilities that allow tissue fluid from the wound to be absorbed, speeding up wound closure. The antibacterial activity of MNs was investigated against S. aureus and E. coli. The results revealed that the developed CUR-loaded MNs had increased antioxidant activity and sustained drug release behavior. Furthermore, after being loaded in the developed MNs, it revealed improved antibacterial activity of CUR. Wound healing potential was assessed by histopathological analysis and wound closure%. The observed results suggest that the CUR-loaded MNs greatly improved wound healing potential via tissue regeneration and collagen deposition, demonstrating the potential of developed MNs patches to be used as an effective carrier for wound healing in healthcare settings.

Molecular Insights into the In Vivo Analgesic and Anti-Inflammatory Activity of Indomethacin Analogues.

The primary objective of this research was to identify and explore the most potent and efficacious cyclooxygenase inhibitors, utilizing indole acetic acid drugs as a lead molecule. To achieve this objective, various derivatives (2a-2c and 2e-2g) of the selected lead molecule, indomethacin, were synthesized using a reflux condensation process, targeting the hydroxyl group. The synthesized analogues were subjected to different spectroscopic procedures to determine their structure and confirm their analogues. These derivatives were further screened for acute toxicity and anti-nociceptive and anti-inflammatory activity using established protocols. Docking analysis was performed to evaluate the possible protein-ligand interaction. The test compounds were found to be safe at doses of 50, 75, 100, and 200 mg/kg, i.p. The pharmacological screening revealed that test compounds 2a-2f had a superior peripheral analgesic effect at a dose of 10 mg/kg, in comparison to the parent drug indomethacin, while compound 2g exhibited slightly lower activity at the same dose. The hot plate results showed lower central analgesic activity of the test compounds compared to the standard Tramal, but it was still significant. Anti-inflammatory results were significant, comparable to Diclofenac sodium and indomethacin, except for compounds 2b, 2c, and 2e at a dose of 10 mg/kg body weight. Molecular docking analysis demonstrated that the derived compounds had augmented negative binding energies (-149.39, -146.72, -160.85, -159.34, -140.03, and -150.91 KJ/mol) compared to the parent drugs (-141.07), which supported the research's theme of producing stronger derivatives of standard drugs with significant anti-nociceptive and anti-inflammatory potential. The derived compounds exhibited significant analgesic and anti-inflammatory activities and, therefore, have the potential to be studied further as new drug candidates for pain and inflammation.

Azole and 5-nitroimidazole based nanoformulations are potential antiamoebic drug candidates against brain-eating amoebae.

AIM: Herein, the anti-parasitic activity of azoles (fluconazole and itraconazole) and 5-nitroimdazole (metronidazole) against the brain-eating amoebae: Naegleria fowleri and Balamuthia mandrillaris was elucidated. METHODS AND RESULTS: Azoles and 5-nitroimidazole based nanoformulations were synthesized and characterized using a UV-visible spectrophotometer, atomic force microscopy, and fourier transform infrared spectroscopy. H1-NMR, EI-MS, and ESI-MS were performed to determine their molecular mass and elucidate their structures. Their size, zeta potential, size distribution, and polydispersity index (PDI) were assessed. Amoebicidal assays revealed that all the drugs and their nanoformulations, (except itraconazole) presented significant anti-amoebic effects against B. mandrillaris, while all the treatments indicated notable amoebicidal properties against N. fowleri. Amoebicidal effects were radically enhanced upon conjugating the drugs with nanoparticles. The IC50 values for KM-38-AgNPs-F, KM-20-AgNPs-M, and KM-IF were 65.09, 91.27, and 72.19 µg.mL-1, respectively, against B. mandrillaris. Whereas against N. fowleri, the IC50 values were: 71.85, 73.95, and 63.01 µg.mL-1, respectively. Additionally, nanoformulations significantly reduced N. fowleri-mediated host cell death, while nanoformulations along with fluconazole and metronidazole considerably reduced Balamuthia-mediated human cell damage. Finally, all the tested drugs and their nanoformulations revealed limited cytotoxic activity against human cerebral microvascular endothelial cell (HBEC-5i) cells. CONCLUSION: These compounds should be developed into novel chemotherapeutic options for use against these distressing infections due to free-living amoebae, as currently there are no effective treatments.

Antibacterial Properties of Ethacridine Lactate and Sulfmethoxazole Loaded Functionalized Graphene Oxide Nanocomposites.

The emergence of drug-resistant bacterial strains that reduce the effectiveness of antimicrobial agents has become a major ongoing health concern in recent years. It is therefore necessary to find new antibacterials with broad-spectrum activity against both Gram-positive and Gram-negative bacteria, and/or to use nanotechnology to boost the potency of already available medications. In this research, we examined the antibacterial efficacy of sulfamethoxazole and ethacridine lactate loaded two-dimensional glucosamine functionalized graphene-based nanocarriers against a range of bacterial isolates. Graphene oxide was first functionalized with glucosamine, which as a carbohydrate moiety can render hydrophilic and biocompatible characters to the GO surface, and subsequently loaded with ethacridine lactate and sulfamethoxazole. The resulting nanoformulations had distinct, controllable physiochemical properties. By analyzing the formulation using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (PXRD), a thermogravimetric analysis (TGA), zetasizer, and a morphological analysis using Scanning Electron Microscopy and Atomic Force Microscopy, researchers were able to confirm the synthesis of nanocarriers. Both nanoformulations were tested against Gram-negative bacteria, including Escherichia coli K1, Serratia marcescens, Pseudomonas aeruginosa, Salmonella enterica, as well as Gram-positive bacteria, including Bacillus cereus, Streptococcus pyogenes, and Streptococcus pneumoniae. Importantly, ethacridine lactate and its nanoformulations exhibited significant antibacterial properties against all bacteria tested in this study. When tested for minimum inhibitory concentration (MIC), the results were remarkable and revealed that ethacridine lactate presented MIC90 at 9.7 µg/mL against S. enteric, and MIC90 at 6.2 µg/mL against B. cereus. Notably, ethacridine lactate and its nanoformulations showed limited toxicity effects against human cells using lactate dehydrogenase assays. Overall, the results revealed that ethacridine lactate and its nanoformulations possess antibacterial activities against various Gram-negative and Gram-positive bacteria and that nanotechnology can be employed for the targeted delivery of effective drugs without harming the host tissue.

Anti-Balamuthia mandrillaris and anti-Naegleria fowleri effects of drugs conjugated with various nanostructures.

Balamuthia mandrillaris and Naegleria fowleri are protist pathogens that can cause fatal infections. Despite mortality rate of > 90%, there is no effective therapy. Treatment remains problematic involving repurposed drugs, e.g., azoles, amphotericin B and miltefosine but requires early diagnosis. In addition to drug discovery, modifying existing drugs using nanotechnology offers promise in the development of therapeutic interventions against these parasitic infections. Herein, various drugs conjugated with nanoparticles were developed and evaluated for their antiprotozoal activities. Characterizations of the drugs' formulations were accomplished utilizing Fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology. The nanoconjugates were tested against human cells to determine their toxicity in vitro. The majority of drug nanoconjugates exhibited amoebicidal effects against B. mandrillaris and N. fowleri. Amphotericin B-, Sulfamethoxazole-, Metronidazole-based nanoconjugates are of interest since they exhibited significant amoebicidal effects against both parasites (p < 0.05). Furthermore, Sulfamethoxazole and Naproxen significantly diminished host cell death caused by B. mandrillaris by up to 70% (p < 0.05), while Amphotericin B-, Sulfamethoxazole-, Metronidazole-based drug nanoconjugates showed the highest reduction in host cell death caused by N. fowleri by up to 80%. When tested alone, all of the drug nanoconjugates tested in this study showed limited toxic effects against human cells in vitro (less than 20%). Although these are promising findings, prospective work is warranted to comprehend the mechanistic details of nanoconjugates versus amoebae as well as their in vivo testing, to develop antimicrobials against the devastating infections caused by these parasites.

Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties.

Given the opportunity and access, pathogenic protists (Balamuthia mandrillaris and Naegleria fowleri) can produce fatal infections involving the central nervous system. In the absence of effective treatments, there is a need to either develop new antimicrobials or enhance the efficacy of existing compounds. Nanocarriers as drug delivery systems are gaining increasing attention in the treatment of parasitic infections. In this study, novel nanocarriers conjugated with amphotericin B and curcumin were evaluated for anti-amoebic efficacy against B. mandrillaris and N. fowleri. The results showed that nanocarrier conjugated amphotericin B exhibited enhanced cidal properties against both amoebae tested compared with the drug alone. Similarly, nanocarrier conjugated curcumin exhibited up to 75% cidal effects versus approx. 50% cidal effects for curcumin alone. Cytopathogenicity assays revealed that the pre-treatment of both parasites with nanoformulated-drugs reduced parasite-mediated host cellular death compared with the drugs alone. Importantly, the cytotoxic effects of amphotericin B on human cells alone were reduced when conjugated with nanocarriers. These are promising findings and further suggest the need to explore nanocarriers as a means to deliver medicine against parasitic infections.

Development of SARS-CoV-2 Vaccine: Challenges and Prospects.

The WHO declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020, which was caused by novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). SARS-CoV-2 made its first entry into the world in November 2019, and the first case was detected in Wuhan, China. Mutations in the SARS-CoV-2 genome distressed life in almost every discipline by the extended production of novel viral variants. In this article, authorized SARS-CoV-2 vaccines including mRNA vaccines, DNA vaccines, subunit vaccines, inactivated virus vaccines, viral vector vaccine, live attenuated virus vaccines and mix and match vaccines will be discussed based on their mechanism, administration, storage, stability, safety and efficacy. The information was collected from various journals via electronic searches including PubMed, Science Direct, Google Scholar and the WHO platform. This review article includes a brief summary on the pathophysiology, epidemiology, mutant variants and management strategies related to COVID-19. Due to the continuous production and unsatisfactory understanding of novel variants of SARS-CoV-2, it is important to design an effective vaccine along with long-lasting protection against variant strains by eliminating the gaps through practical and theoretical knowledge. Consequently, it is mandatory to update the literature through previous and ongoing trials of vaccines tested among various ethnicities and age groups to gain a better insight into management strategies and combat complications associated with upcoming novel variants of SARS-CoV-2.

Investigating the self-assembling of nicotinic hydrazide-based amphiphile into nano-range vesicles and its amphotericin B loading applications.

Most of the drugs are hydrophobic and have low water solubility, therefore posing issues in their absorption and bioavailability. Nonionic surfactants improve the solubility of hydrophobic drugs by entrapping them in their lipid bilayers. Two nonionic surfactants NODNH-16 and NODNH-18 are synthesized and characterized using different techniques i.e. EI-MS, 1H NMR, and FTIR. These newly synthesized surfactants were screened for blood hemolysis assay and cell toxicity studies using the NIH/3T3 cell line to assess their biocompatibility. Then amphotericin B was loaded into niosomal vesicles, and the drug entrapment efficiency of these surfactants was measured using UV-visible spectroscopy. The morphology of drug-loaded niosomes of synthesized surfactants was investigated using AFM, and their size, polydispersity, and zeta potential were measured with the Zetasizer instrument. Finally, a simulation study was performed to determine the pattern of self-assembly of the synthesized amphiphiles. Both synthesized nonionic surfactants showed good entrapment efficiency of 60.65 ± 2.12% and 68.45 ± 2.12%, respectively. It was also confirmed that both these synthesized nonionic surfactants were safe and biocompatible and showed less blood hemolysis (i.e. 21.13 ± 2.11% and 23.32 ± 2.45%) and higher 3T3 cells' viability at 150 µg/mL concentration as compared to Tween®-80. The antifungal potential of amphotericin B-loaded niosomes has been evaluated against unicellular multi-fungal species, which showed a promising potential for fungicidal activity. These results are substantiated by constructing a safe vehicle system for drug delivery.

Improving curcumin bactericidal potential against multi-drug resistant bacteria via its loading in polydopamine coated zinc-based metal-organic frameworks.

Multi-drug resistant (MDR) bactearial strains have posed serious health issues, thus leading to a significant increase in mortality, morbidity, and the expensive treatment of infections. Metal-organic frameworks (MOFs), comprising metal ions and a variety of organic ligands, have been employed as an effective drug deliveryy vehicle due to their low toxicity, biodegradability, higher structural integrity and diverse surface functionalities. Polydopamine (PDA) is a versatile biocompatible polymer with several interesting properties, including the ability to adhere to biological surfaces. As a result, modifying drug delivery vehicles with PDA has the potential to improve their antimicrobial properties. This work describes the preparation of PDA-coated Zn-MOFs for improving curcumin's antibacterial properties against S. aureus and E. coli. Powder X-ray diffraction (P-XRD), FT-IR, scanning electron microscopy (SEM), and DLS were utilized to characterize PDA-coated Zn-MOFs. The curcumin loading and in vitro release of the prepared MOFs were also examined. Finally, the MOFs were tested for bactericidal ability against E. coli and S. aureus using an anti-bacterial assay and surface morphological analysis. Smaller size MOFs were capable of loading and releasing curcumin. The findings showed that as curcumin was encapsulated into PDA-coated MOFs, its bactericidal potential was significantly enhanced, and the findings were further supported by SEM which indicated the complete morphological distortion of the bacteria after treatment with PDA-Cur-Zn-MOFs. These studies clearly indicate that the PDA-Cur-Zn-MOFs developed in this study are extremely promising for long-term release of drugs to treat a wide range of microbial infections.

Cinnamic acid and lactobionic acid based nanoformulations as a potential antiamoebic therapeutics.

Acanthamoeba castellanii causes granulomatous amoebic encephalitis, an uncommon but severe brain infection and sight-threatening Acanthamoeba keratitis. Most of the currently used anti-amoebic treatments are not always effective, due to persistence of the cyst stage, and recurrence can occur. Here in this study we synthesize cinnamic acid and lactobionic acid-based magnetic nanoparticles (MNPs) using co-precipitation technique. These nanoformulations were characterized by Fourier transform infrared spectroscopy and Atomic form microscopy. The drugs alone (Hesperidin, Curcumin and Amphotericin B), magnetic NPs alone, and drug-loaded nano-formulations were evaluated at a concentration of 100 µg/mL for antiamoebic activity against a clinical isolate of A. castellanii. Amoebicidal assays revealed that drugs and conjugation of drugs and NPs further enhanced amoebicidal effects of drug-loaded nanoformulations. Drugs and drug-loaded nanoformulations inhibited both encystation and excystation of amoebae. In addition, drugs and drug-loaded nanoformulations inhibited parasite binding capability to the host cells. Neither drugs nor drug-loaded nanoformulations showed cytotoxic effects against host cells and considerably reduced parasite-mediated host cell death. Overall, these findings imply that conjugation of medically approved drugs with MNPs produce potent anti-Acanthamoebic effects, which could eventually lead to the development of therapeutic medications.

Nanosponges-based Drug Delivery System for the Cosmeceutical Applications of Stabilized Ascorbic Acid.

BACKGROUND: L-Ascorbic acid (AA) is a highly unstable compound, thus, limiting its use in pharmaceutical and cosmetic products, particularly at higher concentrations. OBJECTIVE: This study aimed to stabilize the highly sensitive molecule (AA) by encapsulating it in ß- cyclodextrin nanosponges (ß-CD NS) that can be used further in preparing cosmeceuticals products with higher AA concentrations and enhanced stability. METHODS: The NS has been synthesized by the melting method. The AA was encapsulated in ß-CD NS by the freeze-drying process. The prepared NS were characterized by FTIR spectrometry, SEM, Atomic Force Microscopy (AFM), zeta sizer, Differential Scanning Calorimetry (DSC), and the physical flow characteristics were also studied. The in vitro drug release was carried out on the Franz apparatus using a combination of two methods: sample & separate and dialysis membrane. The assay was performed using a validated spectrometric method. RESULTS: The entrapment efficiency of AA in ß-CD NS indicated a good loading capacity (83.57±6.35%). The FTIR, SEM, AFM, and DSC results confirmed the encapsulation of AA in ß-CD NS. The particle size, polydispersity index, and zeta potential results ascertained the formation of stabilized monodisperse nanoparticles. The physical flow characteristics showed good flow properties. Around 84% AA has been released from the NS in 4 h following the Korsmeyer-Peppas model. The AA-loaded NS remained stable for nine months when stored at 30±2°C/65±5% RH. CONCLUSION: It is concluded that the prepared NS can protect the highly sensitive AA from degradation and provide an extended-release of the vitamin. The prepared AA-loaded ß-CD NS can be used to formulate other cosmeceutical dosage forms with better stability and effect.

Synthetic star shaped tetra-tailed biocompatible supramolecular amphiphile as an efficient nanocarrier for Amphotericin B.

Macrocycle-based amphiphiles are capable of self-assembling into multidimensional nano-architecture with defined dimensions for various applications. Herein we report the synthesis, physio-chemical characterizations and oral drug delivery profiling of resorcinarene-based amphiphilic supramolecular macrocycle. The macrocycle was synthesized in two-step reaction and characterized using 1H NMR, Mass spectrometry and IR spectroscopic techniques. The synthesized macrocycle was assessed for vesicles formation, checked for biocompatibility and then Amphotericin B (Amp-B) was entrapped in macrocycle-based vesicles. The drug loaded vesicles were characterized for shape, size, homogeneity, drug entrapment, surface charge, in-vitro release profile and stability. Amp-B loaded macrocycle based vesicles were examined in rabbits for in-vivo bioavailability and compared with plan drug suspension. The synthesized macrocycle was non-toxic in normal mouse fibroblast cells, compatible with blood and safe in mice. The drug loaded macrocycle based vesicles appeared spherical with 279.4 nm size and - 12.2 mV zeta potential loading 85.45 % drug. The drug loaded vesicles storage stability for 30 days and gastric fluid stability for 1 h were it retained nearly 90 % drug at 30th day and 83.79 % drug at 1 h in gastric fluid. Oral bioavailability of Amp-B in rabbits was markedly enhanced when delivered in synthesized macrocycle based vesicles in comparison with plan drug suspension. Results of this study indicate that the synthesized star shaped tetra-tailed supramolecular amphiphile could be used as an efficient nanocarrier for enhancing oral bioavailability of drugs with solubility and bioavailability issues like Amp-B.

Antiamoebic Properties of Ceftriaxone and Zinc-Oxide-Cyclodextrin-Conjugated Ceftriaxone.

Acanthamoeba castellanii is a ubiquitous free-living amoeba capable of instigating keratitis and granulomatous amoebic encephalitis in humans. Treatment remains limited and inconsistent. Accordingly, there is a pressing need for novel compounds. Nanotechnology has been gaining attention for enhancing drug delivery and reducing toxicity. Previous work has shown that various antibiotic classes displayed antiamoebic activity. Herein, we employed two antibiotics: ampicillin and ceftriaxone, conjugated with the nanocarrier zinc oxide and ß-cyclodextrin, and tested them against A. castellanii via amoebicidal, amoebistatic, encystment, excystment, cytopathogenicity, and cytotoxicity assays at a concentration of 100 µg/mL. Notably, zinc oxide ß-cyclodextrin ceftriaxone significantly inhibited A. castellanii growth and cytopathogenicity. Additionally, both zinc oxide ß-cyclodextrin ceftriaxone and ceftriaxone markedly inhibited A. castellanii encystment. Furthermore, all the tested compounds displayed negligible cytotoxicity. However, minimal anti-excystment or amoebicidal effects were observed for the compounds. Accordingly, this novel nanoconjugation should be employed in further studies in hope of discovering novel anti-Acanthamoeba compounds.