Sohaib Khan

Helicobacter pylori infections demand innovative therapeutic strategies due to rising antibiotic resistance. This review consolidates recent advances in nanoparticle (NP)-based drug delivery systems engineered to optimize antimicrobial efficacy against H. pylori. We critically examine the design, functionality, and performance of metallic, polymeric, lipid-based, and biomimetic nano-carriers, highlighting their advantages over conventional antibiotic delivery. Key innovations include: Lipid-based systems enabling synergistic co-delivery of hesperidin (0.064 μg mL⁻¹) and clarithromycin (0.15 mg mL⁻¹) for enhanced drug bioavailability; Polymeric NPs (e.g. rhamnolipid-chitosan hybrids) achieving deep biofilm penetration ( > 99% eradication) within gastric mucus at minimal inhibitory concentrations (32-132 µg/mL). These nanoplatforms demonstrate precision gastric-mucosa targeting, improved penetration of biological barriers, and controlled antimicrobial release. By maximizing localized drug delivery while minimizing systemic exposure, NP-based systems address critical limitations of current therapies, including resistance and microbiota disruption. We further emphasize the need for clinical validation to translate these delivery technologies into standardized treatments, ultimately reducing the global burden of H. pylori-associated diseases.

Background Recent data shows safety and efficacy of dual-drug regimens (2DR). We evaluated viro-immunological characteristics in gut-associated lymphoid tissues (GALT) and peripheral blood mononuclear cells (PBMCs) in individuals switched to 2DR or maintaining triple-ART (3DR). Methods Eleven virologically suppressed individuals for a median of >2-years were analyzed: 7 individuals in 2DR and 4 in 3DR, for a median time of 23.9 and 94 months, respectively. A rectal biopsy was collected during high resolution anoscopy, and mononuclear cells were isolated from peripheral whole-blood. Total HIV-DNA and cell-associated-HIV-RNA (ca-HIV-RNA) were quantified by droplet-digital-PCR and normalized in 106CD4+ T-cells. The transcriptional activity of HIV-DNA was evaluated by the ratio of ca-HIV-RNA copies/DNA copies. Lymphocyte phenotypes and ART drug concentrations were also analyzed in both compartments. Results Nine out of 11 individuals were male (81.8%), with median age of 35 (interquartile range [IQR] 30–42) years. Individuals were taking ART for a median of 75.5(IQR 57–94.5) months, with undetectable HIV-1-RNA for 45.5(IQR 30.0–62.5) months. The median [IQR] CD4+ and CD8+ counts, and CD4+/CD8+ ratio was 809 [734–874] cells/µL, 663 [521–863] cells/µL and 1.2[0.9–1.3], respectively. Higher HIV-DNA levels were observed in PBMCs compared to GALT (median [IQR] 1175[965–2220] vs 601[408.7–854.5] copies/106CD4, p=0.005), results confirmed also in individuals with 2DR and 3DR (figure 1 - Panel A). Conversely, caHIV-RNA was similar in GALT and PBMCs (figure 1 - Panel B). Interestingly, we found significantly higher HIV-DNA transcriptional activity in GALT compared to PBMCs (median [IQR] 9.9[6.1–16.1] vs 4.3[2.4–6.1) ca-HIV-RNA copies/DNA copies (p=0.02), 2DR (p=0.1) and, 3DR (p=0.03) (figure 1 - Panel C). The higher transcriptional activity in GALT suggests lower penetration of drugs into the tissues, which indeed was confirmed by a lower dolutegravir concentration in GALT (p=0.0007) (figure 1 - Panel D). Furthermore, we observed a trend of weak positive correlation between HIV-DNA and ca-HIV-RNA in PBMCs and GALT (figure 1 - Panel E). Peripheral HIV-DNA negatively correlated with peripheral CD4+ (figure 1 - Panel F), while GALT caHIV-RNA negatively correlated with GALT CD4+ and nadir CD4+ counts (figure 1 -Panel G). Interestingly, immunophenotyping showed GALT HIV-DNA transcriptional activity positively correlated with activated lymphocyte subsets CD19+/38+ in the overall population (p=0.003) (figure 1 - Panel H ) and in the participants on 2DR (p=0.01) (figure 1 - Panel I), while no correlation with CD4+/38+, CD8+/38+ has been observed. Conclusion The HIV-DNA transcriptional activity was significantly higher in GALT and positively correlated with activated lymphocyte subsets, indicating tissue-specific differences in transcriptional activity in peripheral compartment respect to GALT. The lower drugs penetration in tissues, may triggers viral and immune activation. A larger study is ongoing to better understand these aspects.

Helicobacter pylori (H. pylori) has occupied a significant place among infectious pathogens and it has been documented as a leading challenge due to its higher resistance to the commonly used drugs...

Driven by the need to find alternatives to control H. pylori infections, this work describes the development of chitosan-PMLA nanoparticulate systems as carriers for antimicrobial glycolipid. By using a simple ionic gelation method stable nanoparticle was obtained showing an encapsulation efficiency of 73.1 ± 1.3% and an average size of 217.0 ± 15.6 nm for rhamnolipids chitosan-PMLA nanoparticles (RL-CS-NPs). Glycolipid incorporation and particle size were correspondingly corroborated by FT-IR and TEM analysis. Rhamnolipids chitosan nanoparticles (RL-CS-NPs) presented the highest antimicrobial effect towards H. pylori (ATCC 26695) exhibiting a minimal inhibitory concentration of 132 µg/mL and a biofilm inhibition ability of 99%. Additionally, RL-CS-NPs did not interfere with human fibroblasts viability and proliferation under the tested conditions. The results revealed that the RL-CS-NPs were able to inhibit bacterial growth showing adequate cytocompatibility and might become, after additional studies, a valuable approach to fight H. pylori biofilm related-infections.

Pyropia yezoensis is an important marine crop which, due to its high protein content, is widely used as a seafood in China. Unfortunately, red rot disease, caused by Pythium porphyrae, seriously damages P. yezoensis farms every year in China, Japan, and Korea. Proteomic methods are often used to study the interactions between hosts and pathogens. Therefore, an iTRAQ-based proteomic analysis was used to identify pathogen-responsive proteins following the artificial infection of P. yezoensis with P. porphyrae spores. A total of 762 differentially expressed proteins were identified, of which 378 were up-regulated and 384 were down-regulated following infection. A large amount of these proteins were involved in disease stress, carbohydrate metabolism, cell signaling, chaperone activity, photosynthesis, and energy metabolism, as annotated in the KEGG database. Overall, the data showed that P. yezoensis resists infection by inhibiting photosynthesis, and energy and carbohydrate metabolism pathways, as supported by changes in the expression levels of related proteins. The expression data are available via ProteomeXchange with the identifier PXD009363. The current data provide an overall summary of the red algae responses to pathogen infection. This study improves our understanding of infection resistance in P. yezoensis, and may help in increasing the breeding of P. porphyrae-infection tolerant macroalgae.