Tocopherol-human serum albumin nanoparticles enhance lapatinib delivery and overcome doxorubicin resistance in breast cancer.

Introduction: HER2, a tyrosine kinase receptor, is amplified in HER2-positive breast cancer, driving cell signaling and growth. Aim: This study aimed to combat multidrug resistance in Dox-insensitive breast adenocarcinoma by creating a nanoformulation therapy with a tyrosine kinase inhibitor. Methodology: Human serum albumin (HSA) was conjugated with α-D-tocopherol succinate to form nanoaggregates loaded with lapatinib (Lapa). Results: The resulting Lapa@HSA(VE) NPs were 117.2 nm in size and demonstrated IC50 values of 10.25 µg/ml on MCF7 (S) and 8.02 µg/ml on MCF7 (R) cell lines. Conclusion: Lapa@HSA(VE) NPs showed no hepatotoxicity, unlike free Lapa, as seen in acute toxicity studies in rats.

[Box: see text].

Rejoinder to the discussion on "Bayesian meta-analysis of penetrance for cancer risk".

The five discussions of our paper provide several modeling alternatives, extensions, and generalizations that can potentially guide future research in meta-analysis. In this rejoinder, we briefly summarize and comment on some of those points.

Bayesian meta-analysis of penetrance for cancer risk.

Multi-gene panel testing allows many cancer susceptibility genes to be tested quickly at a lower cost making such testing accessible to a broader population. Thus, more patients carrying pathogenic germline mutations in various cancer-susceptibility genes are being identified. This creates a great opportunity, as well as an urgent need, to counsel these patients about appropriate risk-reducing management strategies. Counseling hinges on accurate estimates of age-specific risks of developing various cancers associated with mutations in a specific gene, ie, penetrance estimation. We propose a meta-analysis approach based on a Bayesian hierarchical random-effects model to obtain penetrance estimates by integrating studies reporting different types of risk measures (eg, penetrance, relative risk, odds ratio) while accounting for the associated uncertainties. After estimating posterior distributions of the parameters via a Markov chain Monte Carlo algorithm, we estimate penetrance and credible intervals. We investigate the proposed method and compare with an existing approach via simulations based on studies reporting risks for two moderate-risk breast cancer susceptibility genes, ATM and PALB2. Our proposed method is far superior in terms of coverage probability of credible intervals and mean square error of estimates. Finally, we apply our method to estimate the penetrance of breast cancer among carriers of pathogenic mutations in the ATM gene.

F127/chlorin e6-nanomicelles to enhance Ce6 solubility and PDT-efficacy mitigating lung metastasis in melanoma.

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666 nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors.

Meta-analysis of breast cancer risk for individuals with PALB2 pathogenic variants.

Multigene panel testing now allows efficient testing of many cancer susceptibility genes leading to a larger number of mutation carriers being identified. They need to be counseled about their cancer risk conferred by the specific gene mutation. An important cancer susceptibility gene is PALB2. Multiple studies reported risk estimates for breast cancer (BC) conferred by pathogenic variants in PALB2. Due to the diverse modalities of reported risk estimates (age-specific risk, odds ratio, relative risk, and standardized incidence ratio) and effect sizes, a meta-analysis combining these estimates is necessary to accurately counsel patients with this mutation. However, this is not trivial due to heterogeneity of studies in terms of study design and risk measure. We utilized a recently proposed Bayesian random-effects meta-analysis method that can synthesize estimates from such heterogeneous studies. We applied this method to combine estimates from 12 studies on BC risk for carriers of pathogenic PALB2 mutations. The estimated overall (meta-analysis-based) risk of BC is 12.80% (6.11%-22.59%) by age 50 and 48.47% (36.05%-61.74%) by age 80. Pathogenic mutations in PALB2 makes women more susceptible to BC. Our risk estimates can help clinically manage patients carrying pathogenic variants in PALB2.

Glycol Chitosan-Poly(lactic acid) Conjugate Nanoparticles Encapsulating Ciprofloxacin: A Mucoadhesive, Antiquorum-Sensing, and Biofilm-Disrupting Treatment Modality for Bacterial Keratitis.

Bacterial keratitis (BK) causes visual morbidity/blindness if not treated effectively. Here, ciprofloxacin (CIP)-loaded nanoparticles (NPs) using glycol chitosan (GC) and poly(lactic acid) (PLA) conjugate at three different ratios (CIP@GC(PLA) NPs (1:1,5,15)) were fabricated. CIP@GC(PLA) NPs (1:1) were more effective than other tested ratios, indicating the importance of optimal hydrophobic/hydrophilic balance for corneal penetration and preventing bacterial invasion. The CIP@GC(PLA) (NPs) (1:1) realized the highest association with human corneal epithelial cells, which were nonirritant to the hen's egg-chorioallantoic membrane test (HET-CAM test) and demonstrated significant antibacterial response in the in vitro minimum inhibitory, bactericidal, live-dead cells, zone of inhibition, and biofilm inhibition assays against the keratitis-inducing pathogen Pseudomonas aeruginosa. The antiquorum sensing activity of GC has been explored for the first time. The NPs disrupted the bacterial quorum sensing by inhibiting the production of virulence factors, including acyl homoserine lactones, pyocyanin, and motility, and caused significant downregulation of quorum sensing associated genes. In the in vivo studies, CIP@GC(PLA) NPs (1:1) displayed ocular retention in vivo (∼6 h) and decreased the opacity and the bacterial load effectively. Overall, the CIP@GC(PLA) NP (1:1) is a biofilm-disrupting antiquorum sensing treatment regimen with clinical translation potential in BK.

Mannosylated polyethylenimine-cholesterol-based nanoparticles for targeted delivery of minicircle DNA vaccine against COVID-19 to antigen-presenting cells.

DNA vaccines can be a potential solution to protect global health, triggering both humoral and cellular immune responses. DNA vaccines are valuable in preventing intracellular pathogen infections, and therefore can be explored against coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). This work explored different systems based on polyethylenimine (PEI), functionalized for the first time with both cholesterol (CHOL) and mannose (MAN) to deliver parental plasmid (PP) and minicircle DNA (mcDNA) vectors encoding the receptor-binding domain (RBD) of SARS-CoV-2 to antigen-presenting cells (APCs). For comparative purposes, three different systems were evaluated: PEI, PEI-CHOL and PEI-CHOL-MAN. The systems were prepared at various nitrogen-to-phosphate group (N/P) ratios and characterized in terms of encapsulation efficiency, surface charge, size, polydispersity index (PDI), morphology, and stability over time. Moreover, in vitro transfection studies of dendritic cells (JAWS II) and human fibroblast cells were performed. Viability studies assured the biocompatibility of all nanocarriers. Confocal microscopy studies confirmed intracellular localization of systems, resulting in enhanced cellular uptake using PEI-CHOL and PEI-CHOL-MAN systems when compared with the PEI system. Regarding the RBD expression, PEI-CHOL-MAN was the system that led to the highest levels of transcripts and protein expression in JAWS II cells. Furthermore, the nanosystems significantly stimulated pro-inflammatory cytokines production and dendritic cell maturation in vitro. Overall, mannosylated systems can be considered a valuable tool in the delivery of plasmid DNA or mcDNA vaccines to APCs.

Cationized gelatin-sodium alginate polyelectrolyte nanoparticles encapsulating moxifloxacin as an eye drop to treat bacterial keratitis.

A mucoadhesive polyelectrolyte complex (PEC) nanoparticles were developed for ocular moxifloxacin (Mox) delivery in Bacterial Keratitis (BK). Moxifloxacin-loaded G/CG-Alg NPs were prepared by an amalgamation of cationic polymers (gelatin (G)/cationized gelatin (CG)), and anionic polymer (sodium alginate (Alg)) along with Mox respectively. Mox@CG-Alg NPs were characterized for physicochemical parameters such as particle size (DLS technique), morphology (SEM analysis), DSC, XRD, encapsulation efficiency, drug loading, mucoadhesive study (by texture analyzer), mucin turbidity, and viscosity assessment. The NPs uptake and toxicity of the formulation were analyzed in the Human Corneal Epithelial (HCE) cell line and an ocular irritation study was performed on the HET-CAM. The results indicated that the CG-Alg NPs, with optimal size (217.2 ± 4 nm) and polydispersity (0.22 ± 0.05), have shown high cellular uptake in monolayer and spheroids of HCE. The drug-loaded formulation displayed mucoadhesiveness, trans-corneal permeation, and sustained the release of the Mox. The anti-bacterial efficacy studied on planktonic bacteria/biofilms of P. aeruginosa and S. aureus (in vitro) indicated that the Mox@CG-Alg NPs displayed low MIC, higher zone of bacterial growth inhibition, and cell death compared to free Mox. A significant reduction of bacterial load was observed in the BK-induced mouse model.

Chitosan oligosaccharide/pluronic F127 micelles exhibiting anti-biofilm effect to treat bacterial keratitis.

Mono or dual chitosan oligosaccharide lactate (COL)-conjugated pluronic F127 polymers, FCOL1 and FCOL2 were prepared, self-assembled to form micelles, and loaded with gatifloxacin. The Gati@FCOL1/Gati@FCOL2 micelles preparation process was optimized by QbD analysis. Micelles were characterized thoroughly for size, CMC, drug compatibility, and viscosity by GPC, DLS, SEM, IR, DSC, and XRD. The micelles exhibited good cellular uptake in both monolayers and spheroids of HCEC. The antibacterial and anti-biofilm activities of the micelles were evaluated on P. aeruginosa and S. aureus. The anti-quorum sensing activity was explored in P. aeruginosa by analyzing micelles' ability to produce virulence factors, including AHLs, pyocyanin, and the motility behavior of the organism. Gati@FCOL2 Ms was mucoadhesive, cornea-penetrant, antibacterial, and inhibited the biofilm formation by P. aeruginosa and S. aureus significantly more than Gati@FCOL1. A significant reduction in bacterial load in mice cornea was observed after Gati@FCOL2 Ms-treatment to the P. aeruginosa-induced bacterial keratitis-infected mice.

3D-Printed Inherently Antibacterial Contact Lens-Like Patches Carrying Antimicrobial Peptide Payload for Treating Bacterial Keratitis.

Delivery of therapeutic agents through contact lenses-like patches is a promising strategy to achieve significant bioavailability with negligible eye drainage. The present study investigates the preparation and 3D printing of mucoadhesive gelatin methacryloyl (GelMA)/chitosan methacryloyl (ChiMA) hydrogels to fabricate them as contact lens-like patches (CLP) loaded with antimicrobial peptide, S100A12 (AMP) for treating bacterial keratitis (BK). Extrusion technology is used to print the patches layer by layer to form a hemispherical scaffold suitable for eyewear, and 3D-printed CLP is crosslinked using Irgacure 2959 under UV light. The results from the in vivo experiment conducted on Pseudomonas aeruginosa-infected BK rabbit model after the treatment with AMP-loaded CLP have shown a significant decrease in bacterial load when plated for CFU. The newly developed delivery system containing AMP has great potential to overcome the treatment challenges of multidrug resistance (MDR) in bacteria and eliminate the frequent dosing associated with eye drops. The presence of chitosan in the formulation provides a synergetic effect on the AMP in disrupting bacterial biofilms. The ease of using 3D printing will open new avenues for optimizing the dosage depending on the severity of the BK in the patients, which can be used as personalized medicine.

Meta-Analysis of Breast Cancer Risk for Individuals with PALB2 Pathogenic Variants.

Background: Pathogenic variants in cancer susceptibility genes can now be tested efficiently and economically with the wide availability of multi-gene panel testing. This has resulted in an unprecedented rate of identifying individuals carrying pathogenic variants. These carriers need to be counselled about their future cancer risk conferred by the specific gene mutation. An important cancer susceptibility gene is PALB2. Several studies reported risk estimates for breast cancer (BC) associated with pathogenic variants in PALB2. Because of the variety of modalities (age specific risk, odds ratio, relative risk, and standardized incidence ratio) and effect sizes of these risk estimates, a meta-analysis of all of these estimates of BC risk is necessary to provide accurate counseling of patients with pathogenic variants in PALB2. The challenge, though, in combining these estimates is the heterogeneity of studies in terms of study design and risk measure. Methods: We utilized a recently proposed novel Bayesian random-effects meta-analysis method that can synthesize and combine information from such heterogeneous studies. We applied this method to combine estimates from twelve different studies on BC risk for carriers of pathogenic PALB2 mutations, out of which two report age-specific penetrance, one reports relative risk, and nine report odds ratios. Results: The estimated overall (meta-analysis based) risk of BC is 12.80% by age 50 (6.11%- 22.59%) and 48.47% by age 80 (36.05%-61.74%). Conclusion: Pathogenic mutations in PALB2 makes women more susceptible to BC. Our risk estimates can help clinically manage patients carrying pathogenic variants in PALB2.

Human Serum Albumin-Oxaliplatin (Pt(IV)) prodrug nanoparticles with dual reduction sensitivity as effective nanomedicine for triple-negative breast cancer.

Nanomedicines have emerged as a potential strategy to reduce the toxic effect of drugs administered via conventional approaches. Nanomedicines undergo passive and active targeting of the tumor tissues, thereby causing localized drug delivery and reducing drug demand and side effects. Here, we prepared reduction-sensitive oxaliplatin-conjugated human serum albumin nanoparticles with a small size, uniform surfaces, and a satisfactory encapsulation coefficient. The findings of cellular studies demonstrate that utilizing human serum albumin is effective for active tumor targeting. The presence of glutathione-sensitive disulfide linkers in the crosslinking agent and between Pt(IV) and HSA provided dual reduction sensitivity. Cytotoxicity and cell death were enhanced compared to free Oxaliplatin. The outcomes demonstrate that the approach maximized Oxaliplatin's ability to control tumor growth, induced apoptosis, and reduced drug resistance. Therefore, for the first time, our results imply that OXA-SS-HSA NPs were biocompatible, smart, and effective anticancer nanomedicine for triple-negative breast cancer therapy.

Ameliorative anticancer effect of dendrimeric peptide modified liposomes of letrozole: In vitro and in vivo performance evaluations.

Letrozole (LTZ) loaded dendrimeric nano-liposomes were prepared for targeted delivery to breast cancer cells. Surface modification with cationic peptide dendrimers (PDs) and a cancer specific ligand, transferrin (Tf), was attempted. Arginine-terminated PD (D-1) and Arginine-terminated, lipidated PD (D-2) were synthesized using Solid Phase Peptide Synthesis, purified by preparative HPLC and characterized using 1HNMR, MS and DSC analyses. Surface modification of drug loaded liposomes with Tf and/or PD was carried out. Formulations were characterized using FTIR, DSC, 1HNMR, XRD and TEM. Tf-conjugated LTZ liposomes (LTf) and Tf/D-2-conjugated LTZ liposomes (LTfD-2) showed greater cytotoxic potential (IC50 = 95.03 µg/mL and 23.75 µg/mL respectively) with enhanced cellular uptake in MCF7 cells compared to plain LTZ. Blocking studies of Tf (Tf-receptor mediated internalization) revealed decreased uptake of LTf and LTfD-2 confirming the role of Tf in uptake of Tf-conjugated liposomes. Intravenous treatment with LTfD-2 caused highest reduction in tumor volumes of female BALB/c-nude mice (145 mm3) compared to plain LTZ (605 mm3) and unconjugated LTZ liposomes (LP) (300 mm3). In vivo biodistribution studies revealed higher fluorescence in tumor tissue and liver of LTfD-2 treated mice than LTf or LP treatment. Immunohistochemical studies revealed greater apoptotic potential of LTfD-2 as indicated by TUNEL assay and ROS detection assay. The study reveals the superior therapeutic efficacy of the developed LTZ liposomal nanocarriers using PDs to enhance the transfection efficiency in addition to modifying the surface characteristics by attaching a targeting ligand for active drug targeting to breast cancer cells.

Advances in the Delivery and Development of Epigenetic Therapeutics for the Treatment of Cancer.

Gene expression at the transcriptional level is altered by epigenetic modifications such as DNA methylation, histone methylation, and acetylation, which can upregulate, downregulate, or entirely silence genes. Pathological dysregulation of epigenetic processes can result in the development of cancer, neurological problems, metabolic disorders, and cardiovascular diseases. It is of promising therapeutic interest to find medications that target these epigenetic alterations. Despite the enormous amount of work that has been done in this area, very few molecules have been approved for clinical purposes. This article provides a comprehensive review of recent advances in epigenetic therapeutics for cancer, with a specific focus on emerging delivery and development strategies. Various delivery systems, including pro-drugs, conjugated molecules, nanoparticles (NPs), and liposomes, as well as remedial strategies such as combination therapies, and epigenetic editing, are being investigated to improve the efficacy and specificity of epigenetic drugs (epi-drugs). Furthermore, the challenges associated with available epi-drugs and the limitations of their translation into clinics have been discussed. Target selection, isoform selectivity, physiochemical properties of synthesized molecules, drug screening, and scalability of epi-drugs from preclinical to clinical fields are the major shortcomings that are addressed. This Review discusses novel strategies for the identification of new biomarkers, exploration of the medicinal chemistry of epigenetic modifiers, optimization of the dosage regimen, and design of proper clinical trials that will lead to better utilization of epigenetic modifiers over conventional therapies. The integration of these approaches holds great potential for improving the efficacy and precision of epigenetic treatments, ultimately benefiting cancer patients.

Selective HDAC3 Inhibitors with Potent In Vivo Antitumor Efficacy against Triple-Negative Breast Cancer.

HDAC3 modulation shows promise for breast cancer, including triple-negative cases. Novel pyrazino-hydrazide-based HDAC3 inhibitors were designed and synthesized. Lead compound 4i exhibited potent HDAC3 inhibition (IC50 = 14 nM) with at least 121-fold selectivity. It demonstrated strong cytotoxicity against triple-negative breast cancer cells (IC50: 0.55 µM for 4T1, 0.74 µM for MDA-MB-231) with least normal cell toxicity. Metabolically stable 4i displayed a superior pharmacokinetic profile. A dose-dependent therapeutic efficacy of 4i was observed in a tumor-bearing mouse model. The biomarker analysis with tumor tissues displayed enhanced acetylation on Ac-H3K9, Ac-H3K27, and Ac-H4K12 compared to Ac-tubulin and Ac-SMC3 indicating HDAC3 selectivity of 4i in vivo. The immunoblotting study with tumor tissue showed upregulation of apoptotic proteins caspase-3, caspase-7, and cytochrome c and the downregulation of proliferation markers Bcl-2, CD44, EGFR, and Ki-67. Compound 4i represents a promising candidate for targeted breast cancer therapy, particularly for cases with triple-negative breast cancer.

A dipyridophenazine Ni(II) dithiolene complex as a dual-acting cancer phototherapy agent activatable within the phototherapeutic window.

A combination of photodynamic therapy (PDT) and photothermal therapy (PTT) within the phototherapeutic window (600-900 nm) can lead to significantly enhanced therapeutic outcomes, surpassing the efficacy observed with PDT or PTT alone in cancer phototherapy. Herein, we report a novel small-molecule mixed-ligand Ni(II)-dithiolene complex (Ni-TDD) with a dipyridophenazine ligand, demonstrating potent red-light PDT and significant near-infrared (NIR) light mild-temperature PTT activity against cancer cells and 3D multicellular tumour spheroids (MCTSs). The four-coordinate square planar complex exhibited a moderately intense absorption band (ε âˆ¼ 3700 M-1cm-1) centered around 900 nm and demonstrated excellent dark and photostability in an aqueous phase. Ni-TDD induced a potent red-light (600-720 nm) PDT effect on HeLa cancer cells (IC50 = 1.8 µM, photo irritation factor = 44), triggering apoptotic cell death through efficient singlet oxygen generation. Ni-TDD showed a significant intercalative binding affinity towards double-helical calf thymus DNA, resulting in a binding constant (Kb) âˆ¼ 106 M-1. The complex induced mild hyperthermia and exerted a significant mild-temperature PTT effect on MDA-MB-231 cancer cells upon irradiation with 808 nm NIR light. Simultaneous irradiation of Ni-TDD-treated HeLa MCTSs with red and NIR light led to a remarkable synergistic inhibition of growth, exceeding the effects of individual irradiation, through the generation of singlet oxygen and mild hyperthermia. Ni-TDD displayed minimal toxicity towards non-cancerous HPL1D and L929 cells, even at high micromolar concentrations. This is the first report of a Ni(II) complex demonstrating red-light PDT activity and the first example of a first-row transition metal complex exhibiting combined PDT and PTT effects within the clinically relevant phototherapeutic window. Our findings pave the way for designing and developing metal-dithiolene complexes as dual-acting cancer phototherapy agents using long wavelength light for treating solid tumors.

Compaction of Calf Thymus DNA by a Potential One-Head-Two-Tail Surfactant: Properties of Nanomaterials and Biological Testing for Gene Delivery.

A one-head-two-tail cationic surfactant, Dilauryldimethylammonium bromide (DDAB) has shown a great extent of calf thymus DNA (ct-DNA) compaction being adsorbed on the surfaces of negatively charged SiO2 nanoparticles (NPs). DDAB molecules show high adsorption efficiency and induce many positive surface charges per-unit surface area of the SiO2 NPs compared to cationic Gemini (12-6-12) and conventional (DTAB) surfactants in an aqueous medium at pH 7.4, as evident from zeta potential and EDAX data. Transmission electron microscopy and field emission scanning electron microscopy images, along with ethidium bromide exclusion assay and DLS data support the compaction of ct-DNA. Fluorescence microscopic images show that in the presence of SiO2 NPs, DDAB can perform 50% compaction of ct-DNA at a concentration ∼58% and ∼99% lower than that of 12-6-12 and DTAB, respectively. Better ct-DNA compaction by DDAB is evident compared to other Gemini surfactants (12-4-12 and 12-8-12) as well reported before. Time-correlated single photon counting fluorescence intensity decay measurements of a probe DAPI in ct-DNA have revealed the average lifetime value that is decreased by ∼61% at 2.5 µM of DDAB in the presence of SiO2 NPs as compared to a decrease by only ∼29% in its absence, supporting NPs-induced stronger surfactant binding with ct-DNA. Fluorescence lifetime data have also demonstrated the crowding effect of NPs. At 2.5 µM of DDAB, both fast and slow rotational relaxation components of DAPI contribute almost equally to depolarization with the absence of NPs; however, with the presence of NPs, ∼96% weightage of the anisotropy decay is for the fast component. The present DDAB-SiO2 NPs combination has proved to be an excellent gene delivery system based on the cell viability in the mouse mammary gland adenocarcinoma cells (4T1) and human embryonic kidney (HEK) 293 cell lines, and in vitro and in vivo studies.

Facile fabrication of Nishamalaki churna mediated silver nanoparticles with antibacterial application.

Antimicrobial resistance (AMR) is one of the most serious threats to today's healthcare system. The prime factor behind increasing AMR is the formation of complex bacterial biofilms which acts as the protective shield between the bacterial cell and the antimicrobial drugs. Among various nanoformulations, green synthesized metallic silver nanoparticles are currently gaining research focus in safely breaking bacterial biofilms due to the inherent antimicrobial property of silver. In the current work, the aqueous extract of the ayurvedic formulation Nishamalaki churna is used to exhibit one pot green synthesis of silver nanoparticles. The physicochemical characteristics of Nishamalaki churna extract mediated AgNPs were evaluated using various analytical techniques, like UV-Visible spectrophotometer, FT-IR spectroscopy, SEM, XRD, DLS-Zeta potential analyzer etc. The synthesized spherical AgNPs were well formed within the size range of 30 nm to 80 nm. Furthermore, the synthesized AgNPs showed potent antibacterial effects against two primary AMR-causing bacterial species like Staphylococcus aureus and Pseudomonas aeruginosa with the successful destruction of their biofilm formation. Additionally, these AgNPs have shown profound antioxidant and anti-inflammatory activities as desirable add-on effects required by a prospective antibacterial agent.

Next-Generation Nanomedicine Approaches for the Management of Retinal Diseases.

Retinal diseases are one of the leading causes of blindness globally. The mainstay treatments for these blinding diseases are laser photocoagulation, vitrectomy, and repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) or steroids. Unfortunately, these therapies are associated with ocular complications like inflammation, elevated intraocular pressure, retinal detachment, endophthalmitis, and vitreous hemorrhage. Recent advances in nanomedicine seek to curtail these limitations, overcoming ocular barriers by developing non-invasive or minimally invasive delivery modalities. These modalities include delivering therapeutics to specific cellular targets in the retina, providing sustained delivery of drugs to avoid repeated intravitreal injections, and acting as a scaffold for neural tissue regeneration. These next-generation nanomedicine approaches could potentially revolutionize the treatment landscape of retinal diseases. This review describes the availability and limitations of current treatment strategies and highlights insights into the advancement of future approaches using next-generation nanomedicines to manage retinal diseases.