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Shubham Kanaujiya,1,* Dilip Kumar Arya,1,* Prashant Pandey,1 Sneha Singh,2 Giriraj Pandey,1 Shabnam Anjum,3 Md Meraj Anjum,1 Daoud Ali,4 Saud Alarifi,4 Vijayakumar MR,1 Sri Sivakumar,2 Saurabh Srivastava,5 PS Rajinikanth1 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India; 2Department of Chemical Engineering, IIT Kanpur, Kanpur, India; 3Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, Shenyang, Liaoning, 110122, People’s Republic of China; 4Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia; 5Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India*These authors contributed equally to this workCorrespondence: PS Rajinikanth, Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India, Email psrajinikanth222@gmail.comBackground: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries.Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair.Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31± 0.09 mm and 12± 0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10.Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach. Keywords: electrospinning, nanofiber, resveratrol, ampicillin, burn wound healing, collagen

The increasing contamination of aquatic bodies by heavy metals poses a significant threat to environment and human health, necessitates innovative, sustainable and cost-effective remediation strategies. Due to their persistence and toxicity, heavy metals like copper (Cu), lead (Pb), mercury (Hg), and cadmium (Cd) pose severe threats, even in trace amounts. Traditional removal methods of these heavy metals, like chemical precipitation, oxidation/reduction, filtration, ion exchange, membrane separation, and adsorption, are costly, inefficient, and have drawbacks. As an efficient and low-cost adsorbent, biochar has the potential for heavy metal remediation from water. Biochar is a versatile carbonaceous material produced through pyrolysis of organic wastes, emerged as a powerful adsorbent for heavy metal removal from contaminated water. The unique property of biochar makes it an effective medium immobilizing and capturing of heavy metals like Pb, Cd, As and Hg. Various factors affect its adsorption potential and capacity. Feedstocks type, composition, activation methods, and production processes including the pyrolysis temperature, temperature rate and residence time significantly impact the efficacy of biochar. Therefore, this review has assessed, compared, and contrasted different forms of biochar along with their production methods, modification techniques and mechanisms for their potential use as an adsorbent for heavy metal removal from the contaminated water. Modified biochar offers an environmentally friendly and cost-effective solution for water purification and remediation of toxic heavy metals from water. This review highlights the biochar potential as a crucial component for future research projects focusing on water treatment technologies, providing avenues for safer and cleaner water resources., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

A notable breakthrough in the treatment of colon cancer involves the utilisation of a cutting-edge drug delivery technology known as biosurfactant-derived nanomicelles. These nanomicelles, composed of natural biosurfactant molecules, possess the distinct capability to enclose pharmaceuticals or genetic material, such as DNA, siRNA, or mRNA, within spherical formations. With a size ranging from 10 to 100 nanometers, these nanomicelles exhibit precision targeting capabilities towards colon cancer cells, hence minimising the occurrence of side effects typically associated with treatment. Upon being specifically targeted, the nanomicelles liberate their cargo into cancer cells, resulting in enhanced therapy efficacy. This novel strategy utilises the specific attributes of the tumour microenvironment to administer precise and focused treatment. These nanomicelles improve the absorption by cells and reduce harm to healthy tissues by imitating important nutrients or utilising compounds that specifically target tumours. Furthermore, the incorporation of stimuli-responsive components allows for regulated medication release in reaction to the acidic environment seen in tumours. The review focuses on examining the use of biosurfactants and natural peptides in nanomicellar carriers as ways to fight against colon cancer. Folate-coated nanomicelles incorporating curcumin facilitate precise gene delivery, while the partnership of biosurfactants, such as surfactin from Bacillus subtilis and natural peptides, enables the transportation of particular cyclopeptides into the tumour network. Peptides, similar to bombesin, direct nanomicelles to specific places, while peptides based on curcumin control the release of medicinal substances. While preclinical investigations demonstrate promise, obstacles remain in formulation and regulatory issues. However, biosurfactant-based nanomicelles, particularly folate-coated carriers loaded with curcumin, show tremendous potential in overcoming biological barriers and delivering medicines efficiently to colon cancer cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We present a case of invasive pulmonary aspergillosis in an immunocompetent young female. An 18-year-old female presented with symptoms of a left-sided middle cerebral artery (MCA) stroke with right arm weakness and aphasia. Computed tomography (CT) brain confirmed the diagnosis of stroke. Further history revealed that the patient had been experiencing low-grade fevers with occasional shortness of breath for the past year. The blood work had eosinophilia at that time for which she was given mebendazole but saw little improvement. Chest X-rays showed upper lobe consolidation for which a tuberculosis (TB) workup was also done, which also came out negative. At the current presentation, she underwent further workup with echocardiography and eventual ultrasound-guided mediastinal biopsy that ultimately led to the correct diagnosis of aspergillosis. However, sadly, it was already too late for the patient who passed away one day after the commencement of the amphotericin B therapy. This paper hopes to decrease the threshold of clinical suspicion for invasive aspergillosis (IA) regardless of the immunity status of the patient, especially if they are presenting with an unrelenting mediastinal or pulmonary symptom complex in the setting of eosinophilia., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mian et al.)

Cardiotoxicity (CT) is a severe condition that negatively impacts heart function. β-sitosterol (BS) is a group of phytosterols and known for various pharmacological benefits, such as managing diabetes, cardiac protection, and neuroprotection. This study aims to develop niosomes (NS) containing BS, utilizing cholesterol as the lipid and Tween 80 as the stabilizer. The research focuses on designing and evaluating both conventional BS-NS and hyaluronic acid (HA) modified NS (BS-HA-NS) to enhance the specificity and efficacy of BS within cardiac tissue. The resulting niosomal formulation was spherical, with a size of about 158.51 ± 0.57 nm, an entrapment efficiency of 93.56 ± 1.48 %, and a drug loading of 8.07 ± 1.62 %. To evaluate cytotoxicity on H9c2 heart cells, the MTT assay was used. The cellular uptake of BS-NS and BS-HA-NS was confirmed by confocal microscopy on H9c2 cardiac cells. Administering BS-NS and BS-HA-NS intravenously at a dose of 10 mg/kg showed the ability to significantly decrease the levels of cardiac troponin-I (cTn-I), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and lipid peroxidation (MDA). Tissue histopathology indicated a substantial potential for repairing cardiac tissue after treatment with BS-NS and BS-HA-NS and strong cardioprotection against ISO induced myocardial tissue damages. Thus, enhancing BS's therapeutic effectiveness through niosome surface modification holds promise for mitigating cardiac damage resulting from CT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: Encapsulating epigallocatechin-3-gallate (EGCG) in pH-sensitive polymeric nanoparticles for targeted delivery of drugs could revolutionize colorectal cancer treatment., Materials & Methods: Nanoparticles were synthesized to release drugs at colon pH. Dynamic light scattering measured their average diameter and ζ-potential, while differential scanning calorimetry and x-ray diffraction assessed EGCG encapsulation., Results: The nanoparticles showed stability and bioavailability in the gastrointestinal tract, efficiently encapsulating and releasing over 93% of EGCG at pH 7.2. They enhanced cytotoxicity against HT-29 cells and demonstrated antibacterial properties, increasing apoptosis and cell cycle arrest., Conclusion: The study underscores the potential of nanoparticles in enhancing EGCG delivery for colorectal cancer therapy, aiming to minimize side effects and improve therapeutic outcomes.

Photodynamic therapy (PDT) is a promising cancer treatment that kills cancer cells selectively by stimulating reactive oxygen species generation with photosensitizers exposed to specific light wavelengths. 5-aminolevulinic acid (5-ALA) is a widely used photosensitizer. However, its limited tumour penetration and targeting reduce its therapeutic efficacy. Scholars have investigated nano-delivery techniques to improve 5-ALA administration and efficacy in PDT. This review summarises recent advances in biological host biosynthetic pathways and regulatory mechanisms for 5-ALA production. The review also highlights the potential therapeutic efficacy of various 5-ALA nano-delivery modalities, such as nanoparticles, liposomes, and gels, in treating various cancers. Although promising, 5-ALA nano-delivery methods face challenges that could impair targeting and efficacy. To determine their safety and biocompatibility, extensive preclinical and clinical studies are required. This study highlights the potential of 5-ALA-NDSs to improve PDT for cancer treatment, as well as the need for additional research to overcome barriers and improve medical outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The objective of this investigation was to fabricate nanoparticles consisting of Imatinib mesylate-poly sarcosine-loaded chitosan/carrageenan in order to attain prolonged drug release and efficacious therapy for colorectal cancer. The study involved the synthesis of nanoparticles through the utilisation of ionic complexation and nanoprecipitation techniques. The subsequent nanoparticles were subjected to an assessment of their physicochemical characteristics, anti-cancer efficacy using HCT116 cell line, and acute toxicity. The present study examined two distinct nanoparticle formulations, namely IMT-PSar-NPs and CS-CRG-IMT-NPs, with respect to their particle size, zeta potential, and morphology. Both formulations demonstrated satisfactory characteristics, as they displayed consistent and prolonged drug release for a duration of 24 h, with the highest level of release occurring at a pH of 5.5. The efficacy and safety of IMT-PSar-NPs and CS-CRG-IMT-PSar-NPs nanoparticles were evaluated through various tests including in vitro cytotoxicity, cellular uptake, apoptosis, scratch test, cell cycle analysis, MMP & ROS estimate, acute toxicity, and stability tests. The results suggest that these nanoparticles were well fabricated and have promising potential for in vivo applications. The prepared polysaccharide nanoparticles have great potential for active targeting and could potentially reduce dose-dependent toxicity in the treatment of colon cancer., Competing Interests: Declaration of competing interest Authors declare there are no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The morbidity rate following a surgical procedure increasing rapidly in the cases associated with surgical site infections. Traditional sutures lack the ability to deliver drugs as the incorporation of the drug in their structure would hamper their mechanical properties. To prevent such infections, we developed an extracellular matrix mimicking electrospun nanofibrous yarns of poly-(D,L)-lactic acid and polyvinyl alcohol loaded with vancomycin and ferulic acid, prepared by uniaxial electrospinning technique. In-vitro characterization such as scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, tensile strength testing, degradation studies, and antimicrobial studies along with in-vivo evaluation done with help of incision wound healing rat model and simultaneous testing of microbial load in the incised tissue. The in-vitro studies indicated the nanofiber yarns have size range 200-300 nm with a tensile strength of 7.54 ± 0.58 MPa. The dual drug-loaded yarn showed sustained drug release over a period of 48 h. In-vitro water uptake and biodegradation data indicated optimum results suitable for suturing applications. Antimicrobial study showed excellent antimicrobial activity against both S. aureus and E. coli. Results obtained from in-vivo study suggested excellent wound healing potential of nanofiber yarns as compared with commercial silk sutures. The histopathological studies confirmed restoring ability of nanofiber yarn to the normal skin structure. Enzyme-linked immunosorbent assay (ELISA) study revealed the downregulation of inflammatory markers i.e. TNF-alpha and IL-6, making nanofibers sutures suitable for surgical wound healing applications. Overall, the present study may conclude that the developed dual drug-loaded nanofiber yarns have excellent potential in surgical wound healing applications., (© 2023 IOP Publishing Ltd.)

Psoriasis is an autoimmune skin disease that generally affects 1%-3% of the total population globally. Effective treatment of psoriasis is limited because of numerous factors, such as ineffective drug delivery and efficacy following conventional pharmaceutical treatments. Nanofibers are widely being used as nanocarriers for effective treatment because of their multifunctional and distinctive properties, including a greater surface area, higher volume ratio, increased elasticity and improved stiffness and resistance to traction, favorable biodegradability, high permeability, and sufficient oxygen supply, which help maintain the moisture content of the skin and improve the bioavailability of the drugs. Similar to the extracellular matrix, nanofibers have a regeneration capacity, promoting cell growth, adhesion, and proliferation, and also have a more controlled release pattern compared with that of other conventional therapies at the psoriatic site. To ensure improved drug targeting and better antipsoriatic efficacy, this study formulated and evaluated a tazarotene (TZT)-calcipotriol (CPT)-loaded nanofiber and carbopol-based hydrogel film. The nanofiber was prepared using electrospinning with a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) K-90 polymeric blend that was later incorporated into a carbopol base to form hydrogel films. The prepared nanofibers were biochemically evaluated and in vitro and in vivo characterized. The mean diameters of the optimized formulation, i.e., TZT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-PVA/PVP-NF) and TZT-CPT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-CPT-PVA/PVP-NF) were 244.67 ± 58.11 and 252.31 ± 35.50 nm, respectively, as determined by scanning electron microscopy, and their tensile strength ranged from 14.02 ± 0.54 to 22.50 ± 0.03 MPa. X-ray diffraction revealed an increase in the amorphous nature of the nanofibers. The biodegradability studies of prepared nanofiber formulations, irrespective of their composition, showed that these completely biodegraded within 2 weeks of their application. The TZT-CPT-PVA/PVP-NF nanofibers exhibited 95.68% ± 0.03% drug release at the end of 72 h, indicating a controlled release pattern and following Higuchi release kinetics as a best-fit model. MTT assay, antioxidant and lipid profile tests, splenomegaly assessment, and weight fluctuation were all performed in the in vitro as well as in vivo studies. We found that the TZT-CPT-PVA/PVP-NF-based hydrogel film has high potential for antipsoriatic activity in imiquimod-induced Wistar rats in comparison with that of TT-PVA/PVP-NF nanofibers.

This study focused on gemcitabine (GTB) delivery of cationic polymeric nanoparticles to treat ovarian cancer in order to promote effective localized delivery and drug retention during biological discharge. To begin, four GTB-loaded polymer nanoparticles were prepared: chitosan nanoparticles (CS-NPs), polysarcosin nanoparticles (PSar-NPs), poly-l-lysine & polysarcosin nanoparticles (PLL-PSar-NPs), and chitosan & polysarcosin nanoparticles (CS-PSar-NPs). Based on preliminary particle size, zeta potential, encapsulation efficiency, DSC, surface morphology, release profiling, and cellular internalization studies using rhodamine 123 and Nile red fluorescent markers, it was hypothesized that CS-PSar-NPs could be the best cationic formulation with strong biocompatibility and anticancer activity against the OVCAR-8 ovarian cancer cell line. To improve effective targeting, cellular penetration, and in vitro cytotoxicity, epidermal growth factor receptor variation III (EGFRvIII) is attached over all four polymeric nanoparticles. Confocal imaging revealed that EGFRvIII-conjugated cationic GTB polymeric nanoparticles had a greater cellular uptake and double internalization capabilities than unconjugated nanoparticles, as well as time-dependent cell entrance. GTB and EGFRvIII-conjugated polymer nanoparticles would have a stronger potential to infiltrate ovarian cancer cells during the first hour of incubation. According to TEM and FTIR findings, EGFRvIII conjugation across the non-target CS-PSar-NP surface was successful, making CS-PSar-NPS-EGFRvIII more target-specific and thus a safer drug delivery candidate for ovarian cancer treatment.HighlightsGTB loaded non-target CS-PSar-NPs & active targeted CS-PSar-NPs-EGFRvII developed.SEM, AFM, DSC, particle size, zeta potential, internalization performed for CS-PSar-NPs.MTT & CLSM study confirmed CS-PSar-NPS-EGFRvII was binding specific to OVCAR-8 cellsFabrication of EGFRvII over nanoparticles confirmed by TEM.CS-PSar-NPS-EGFRvII safer candidate for ovarian cancer.

Objectives: This paper developed federated solutions based on two approximation algorithms to achieve federated generalized linear mixed effect models (GLMM). The paper also proposed a solution for numerical errors and singularity issues. And showed the two proposed methods can perform well in revealing the significance of parameter in distributed datasets, comparing to a centralized GLMM algorithm from R package ('lme4') as the baseline model., Methods: The log-likelihood function of GLMM is approximated by two numerical methods (Laplace approximation and Gaussian Hermite approximation, abbreviated as LA and GH), which supports federated decomposition of GLMM to bring computation to data. To solve the numerical errors and singularity issues, the loss-less estimation of log-sum-exponential trick and the adaptive regularization strategy was used to tackle the problems caused by federated settings., Results: Our proposed method can handle GLMM to accommodate hierarchical data with multiple non-independent levels of observations in a federated setting. The experiment results demonstrate comparable (LA) and superior (GH) performances with simulated and real-world data., Conclusion: We modified and compared federated GLMMs with different approximations, which can support researchers in analyzing versatile biomedical data to accommodate mixed effects and address non-independence due to hierarchical structures (i.e., institutes, region, country, etc.)., (© 2022. The Author(s).)

The success behind Machine Learning (ML) methods has largely been attributed to the quality and quantity of the available data which can spread across multiple owners. A Federated Learning (FL) from distributed datasets often provides a reliable solution that provides valuable insight. For a genomic dataset, such data have also proven to be sensitive which requires additional safety mechanisms before any sharing or ML operations. We propose a generalized gene expression data sharing method using a differentially private mechanism. Due to the large number of genes available, the data dimension is also reduced to accommodate smaller privacy budgets as we utilize an exponential mechanism to create a private histogram from numeric expression data. The output histogram can be used in any federated machine learning setting having multiple data owners. The proposed solution was submitted to genomic data security and privacy competition, iDash 2020 where it ranked third among 55 teams. We extend the proposed solution and experimented with two different machine learning algorithms and different settings. The experimental results show that it takes around 8 s to train a model while achieving 0.89 AUC with only a privacy budget of 5. The paper outlined a method to share gene expression data for Federated Learning using a privacy-preserving mechanism. Different experimental settings and recent competition results show the efficacy of the method which can be further extended to other genomic datasets and machine learning algorithms., (Copyright © 2022. Published by Elsevier Inc.)

Background: The present study was intended to comparatively assess the efficacy of ganglioside polymeric nanoparticle-coated 0.25% satranidazole-loaded nanoparticles in gel form with that of the commercially available 1% metronidazole gel as a local drug delivery (LDD) agent for the treatment of periodontal pockets., Materials and Methods: A split-mouth randomized clinical trial was carried out in 46 chronic periodontitis patients with probing pocket depth (PPD) ≥4 mm or clinical attachment loss greater than 3 mm on both quadrants of the same arch. Full-mouth scaling and root planing (SRP) was performed for all the patients followed by application of 0.25% satranidazole-loaded nanoparticles in gel form on one site (Group 1) and commercially available 1% metronidazole gel on another site (Group 2). Clinical parameters (gingival index, plaque index, PPD, clinical attachment level gain, and bleeding on probing) and microbiological analysis of the subgingival plaque samples were performed and assessed at baseline, after SRP, 21 st day, and 90 th day post treatment. Unpaired " t "-test and ANOVA tests were used for intergroup and intragroup comparison of recorded parameters., Results: The results showed that the satranidazole-loaded nanoparticle group as an adjunct to SRP in chronic periodontitis showed a statistically significant improvement in all the clinical parameters and a fewer relapse of microbial flora in comparison with the metronidazole group as an LDD agent., Conclusion: The present study depicted that both the LDD agents showed an effective improvement of clinical as well as microbiological parameters, but the satranidazole group consistently produced better results than the metronidazole group and hence has a promising future as an LDD agent in treating periodontal pockets., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Society of Periodontology.)

Generalized Linear Mixed Model is one of the most pervasive class of statistical models. It is widely used in the medical domain. Training such models in a collaborative setting often entails privacy risks. Standard privacy preserving mechanisms such as differential privacy can be used to mitigate the privacy risk during training the model. However, experimental evidence suggests that adding differential privacy to the training of the model can cause significant utility loss which makes the model impractical for real world usage. Therefore, it becomes clear that the specific class of generalized linear mixed models which lose their usability under differential privacy requires a different approach for privacy preserving model training. In this work, we propose a value-blind training method in a collaborative setting for generalized linear mixed models. In our proposed training method, the central server optimizes model parameters for a generalized linear mixed model without ever getting access to the raw training data or intermediate computation values. Intermediate computation values that are shared by the collaborating parties with the central server are encrypted using homomorphic encryption. Experimentation on multiple datasets suggests that the model trained by our proposed method achieves very low error rate while preserving privacy. To the best of our knowledge, this is the first work that performs a systematic privacy analysis of generalized linear mixed model training in collaborative setting., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Biofilm mediated bacterial infections are the key factors in the progression of infectious diseases due to the evolution of antimicrobial resistance. Traditional therapy involving antibiotics is not adequate enough for treatment of such infections due to the increased resistance triggered by biofilm. To overcome this challenge, we developed anacardic acid (Ana) loaded solid lipid nanoparticles (SLNs), further coated with chitosan and DNase (Ana-SLNs-CH-DNase). The DNase coating was hypothesized to degrade the e-DNA, while chitosan was coated to yield positively charged SLNs with additional adhesion to biofilms. The SLNs were developed using homogenization method and further evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Drug excipient compatibility was confirmed by using FT-IR study, while encapsulation of Ana in SLNs was confirmed by X-ray diffraction study. The SLNs demonstrated sustained release for up to 24 h and excellent stability at room temperature for up to 3 months. The developed SLNs were found non-toxic against human immortalized keratinocyte (HaCaT) cells while demonstrated remarkably higher antimicrobial efficacy against Staphylococcus aureus. Excellent effect of the developed SLNs on minimum biofilm inhibition concentration and minimum biofilm eradication concentration further confirmed the superiority of the developed formulation strategy. A significant (p < 0.05) reduction in biofilm thickness and biomass, as confirmed by confocal laser scanning microscopy, was observed in the case of developed SLNs in comparison with control. Cumulatively, the results suggest the enhanced efficacy of the developed formulation strategy to overcome the biofilm-mediated antimicrobial resistance. Graphical abstract.

Biofilm resistance is one of the severe complications associated with chronic wound infections, which impose extreme microbial tolerance against antibiotic therapy. Interestingly, deoxyribonuclease-I (DNase-I) has been empirically proved to be efficacious in improving the antibiotic susceptibility against biofilm-associated infections. DNase-I hydrolyzes the extracellular DNA, a key component of the biofilm responsible for the cell adhesion and strength. Moreover, silver sulfadiazine, a frontline therapy in burn wound infections, exhibits delayed wound healing due to fibroblast toxicity. In this study, a chitosan gel loaded with solid lipid nanoparticles of silver sulfadiazine (SSD-SLNs) and supplemented with DNase-I has been developed to reduce the fibroblast cytotoxicity and overcome the biofilm-imposed resistance. The extensive optimization using the Box-Behnken design (BBD) resulted in the formation of SSD-SLNs with a smooth surface as confirmed by scanning electron microscopy and controlled release (83%) for up to 24 h. The compatibility between the SSD and other formulation excipients was confirmed by Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffraction studies. Developed SSD-SLNs in combination with DNase-I inhibited around 96.8% of biofilm of Pseudomonas aeruginosa as compared to SSD with DNase-I (82.9%). In line with our hypothesis, SSD-SLNs were found to be less toxic (cell viability 90.3 ± 3.8% at 100 μg/mL) in comparison with SSD (Cell viability 76.9 ± 4.2%) against human dermal fibroblast cell line. Eventually, the results of the in vivo wound healing study showed complete wound healing after 21 days' treatment with SSD-SLNs along with DNase-I, whereas marketed formulations SSD and SSD-LSNs showed incomplete healing after 21 days. Data in hand suggest that the combination of SSD-SLNs with DNase-I is an effective treatment strategy against the biofilm-associated wound infections and accelerates wound healing.

The study was designed to fabricate the moxifloxacin nanostructured lipid carriers (MOX-NLCs) loaded in situ gel for opthalmic application to improve the corneal permeation and retention and also subside the toxic effect associated with intracameral injection of moxifloxacin in endophthalmitis treatment. Initially, Box-Behnken design was used to optimize the various factors significantly affecting the final formulation attributes. MOX-NLCs with particle size 232.1 ± 9.2 nm, polydispersity index 0.247 ± 0.031, zeta potential -16.3 ± 1.6 mV, entrapment efficiency 63.1 ± 2.4%, and spherical shape was achieved. The optimized MOX-NLCs demonstrated the Higuchi release kinetics with highest regression coefficient. Besides this, FTIR, differential scanning calorimetry, and X-ray diffraction results suggested that MOX had excellent compatibility with excipients. Furthermore, the results of ex-vivo permeation study demonstrated 2-fold higher permeation (208.7 ± 17.6 μg), retention (37.26 ± 2.83 μg), and flux (9.57 ± 0.73 μg/cm 2 h) compared with free MOX in situ gel. In addition, MOX-NLCs exhibited normal corneal hydration and did not show any sign of structural damage to the corneal tissue as confirmed by histology. Therefore, the findings strongly suggest that MOX-NLCs in situ gel with higher permeation and retention can be a better alternative strategy to prevent and treat the endophthalmitis infection., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Dense colonization of mucoid Pseudomonas aeruginosa within the self-secreted extracellular matrix (mainly alginate), called biofilm, is a principal reason for the failure of antimicrobial therapy in cystic fibrotic patients. Alginate is a key component in the biofilm of mucoid P. aeruginosa and responsible for surface adhesion and stabilization of biofilm. To overcome this problem, alginate lyase functionalized chitosan nanoparticles of ciprofloxacin were developed for the effective treatment of P. aeruginosa infection in cystic fibrosis patients. The developed nanoparticles were found to have desired quality attributes and demonstrated sustained release following the Higuchi release kinetics. Drug compatibility with the chitosan was confirmed by FTIR while powder X-ray diffraction analysis confirmed the entrapment of drug within the nanoparticle matrix. Lactose adsorbed NPs showed promising aerodynamic property. Nanoparticles showed prolonged MIC and significant reduction in biofilm aggregation and formation in planktonic bacterial suspension. Nanoparticles exhibited significantly higher inhibitory effect against biofilm of P. aeruginosa and reduced the biomass, thickness and density confirmed by confocal microscopy. Furthermore, developed nanoparticles were haemocompatible and did not exhibit any toxicity in vitro MTT assay and in vivo on lungs male Wistar rats. The data in hand collectively suggest the proposed strategy a better alternative for the effective treatment of cystic fibrosis infections., (Copyright © 2019. Published by Elsevier B.V.)