http://digitalrepository.fccollege.edu.pk/handle/123456789/471 Pharmacy Department 2026-06-22T10:10:03Z http://digitalrepository.fccollege.edu.pk/handle/123456789/2777 Title: Mechanochemical Synthesis of Diclofenac Conjugates with Glucosamine and Chitosan Exhibiting COX-2 Selective Ulcer Safe Anti-inflammatory Activity Authors: Khan, Abdul H. Abstract: Introduction: Non-steroidal anti-inflammatory drugs are associated with severe gastrointestinal irritation upon prolonged use, largely due to their carboxylic (- COOH) functional group. Aim: To address this issue, we aimed to synthesize diclofenac conjugates with glucosamine and chitosan, converting the -COOH group into an amide (-CONH-) via a mechanochemical, environmentally friendly method. Methods: In this study, diclofenac acid was first converted to its acid chloride using thionyl chloride under mechanochemical conditions and subsequently reacted with glucosamine base and chitosan. The resulting conjugates were evaluated for anti-inflammatory activity through the rat-paw edema test, along with ulcerogenicity, COX inhibition assays, and cardiovascular assessment. Results: The mechanochemical approach provided high yields (>90%) and resulted in conjugates that significantly reduced paw edema (62.3 ± 2.3% for diclofenac- glucosamine and 58.5 ± 1.6% for diclofenac-chitosan) compared to diclofenac sodium (49.0 ± 1.3%) after 5 h. Notably, the conjugates were ulcer safe, as no gastric lesions were observed, unlike the multiple lesions detected in animals treated with diclofenac sodium. Both conjugates also demonstrated a high degree of COX-2 selectivity and cardiovascular safety. Conclusion: This study highlights the potential of mechanochemical synthesis for efficient amide formation, avoiding the need for hydroxyl group protection. 2024-11-21T00:00:00Z http://digitalrepository.fccollege.edu.pk/handle/123456789/2776 Title: A Study of Pharmaceutical Applications of Hemicelluloses From Nine Food Materials Authors: Khan, Abdul H. Abstract: Objective: This study is aimed at evaluating the release-extending, film-coating, suspending, and thickening properties of various food-derived hemicelluloses, as natural alternatives to synthetic excipients for use in pharmaceutical tablets and suspensions. Background: Hemicelluloses are partially digestible biopolymers with superior biocompatibility, biodegradability, and sustainability compared to synthetic and cellulose-based semisynthetic materials. This study focused on the evaluation of potential application of hemicelluloses as environmentally friendly, highly biocompatible pharmaceutical excipients. Methods: The hemicelluloses were isolated from Acacia nilotica (AN), Lallemantia royleana (LR) seeds, Plantago ovata husk (POh), Plantago ovata seeds (POs), Ocimum basilicum (OB) seeds, Salvia plebian (SP) seeds, Astragalus tragacantha (AT), Mimosa pudica (MP) seeds, Acacia modesta (AM), and Cydonia oblonga (CO). Acetaminophen was used as a model drug. Tablets were prepared via wet granulation and direct compression, and various parameters, including flow, hardness, film- coating strength, and drug release characteristics, were evaluated. Rheology and sedimentation volume were determined for suspensions. Results: The granules for tablets exhibited good flow properties, and the matrix tablets prepared through wet granulation and direct compression exhibited hardness in the range of 2–7 kg cm−2 , with disintegration times between 1.18 and 25.0 min at pH 6.8. Wet granulated tablets released 45%–92% of acetaminophen in ~7 h, and the film coatings showed a strength of 35– 40 kg m s−2 . The suspensions demonstrated excellent stability for over 2 months without the need for redispersion, with sedimentation volumes ranging from 90% to 92%, except for those containing AT. The stability trend for suspensions was observed as SP >OB > AN> AM > CO> Poh > POs > LR > MP > AT. Notably, the prepared suspensions were more stable than the standard Calpol. Conclusion: Hemicelluloses from natural sources show potential as effective tablet binders, extended-release agents, film-coating materials, and suspending/thickening agents in pharmaceutical formulations. These findings highlight their promise as sustainable and biocompatible alternatives to synthetic/semisynthetic excipients. 2025-03-03T00:00:00Z http://digitalrepository.fccollege.edu.pk/handle/123456789/2768 Title: Engineered Cu‐VT composite nanoparticles induce copper‐dependent cell death in bladder cancer: insights from single‐cell spatial transcriptomics Authors: Ali, Dr. Shujaat Abstract: Bladder cancer (BLCA), particularly due to the high recurrence and progression rates of non-muscle-invasive bladder cancer (NMIBC), is a significant global health challenge. Current treatments, such as Bacillus Calmette-Guérin (BCG) immunotherapy and intravesical chemotherapy, often cause substantial side effects and exhibit limited efficacy, highlighting the urgent need for novel therapeutic strategies. Single-cell spatial transcriptomic advancements have identified cuproptosis as a critical pathway in BLCA, presenting a promising target for treatment. In this study, these insights were leveraged to design Cu-VT nanoparticles (NPs), an innovative composite material that combines the unique properties of copper ions and the natural flavonoid vitexin, to induce cuproptosis. Cu-VT NPs could effectively induce apoptosis and oxidative stress in BLCA cells concurrently modulating the immune response within the tumor microenvironment. Comprehensive in vitro and in vivo experiments demonstrated that Cu-VT NPs significantly inhibited tumor growth and reduced lung metastasis through cuproptosis induction. This dual-function composite material enhances therapeutic efficacy and minimizes side effects, showcasing its potential as a revolutionary treatment for BLCA. Our findings highlight the transformative potential of Cu-VT NPs in the context of BLCA treatment, establishing a new paradigm in the use of composite materials for the treatment of advanced cancer. 2024-12-09T00:00:00Z http://digitalrepository.fccollege.edu.pk/handle/123456789/2002 Title: Efficacy of extracts from eight economically important forestry species against grapevine downy mildew (Plasmopara viticola) and identification of active constituents Authors: A. Mulholland, Dulcie; Thuerig, Barbara; K. Langat, Moses; Tamm, Lucius; A. Nawrot, Dorota; E. James, Emily; Qayyum, Mehwish; Shen, Danni; Ennis, Kallie; Jones, Amy; Hokkanen, Heikki; Demidova, Natalia; Izotov, Denis; Scharer, Hans-Jakob Abstract: Downy mildew caused by the oomycete Plasmopara viticola is the most devastating pathogen of grapevine. In this study, extracts of the bark of eight important northern forestry species were screened to find extracts showing activity against this pathogen and to identify the active compounds. Extracts from all eight species showed activity against P. viticola, the most promising, dichloromethane extracts of three Larix species, almost completely protecting grapevine from downy mildew under semi-controlled conditions. Five promising lead compounds were isolated: larixol, larixyl acetate, lariciresinol and lar iciresinol acetate from Larix species and 7a,15-dihydroxydehydroabietic acid from Pinus sylvestris. These compounds showed 90%e100% efficacy. Larixol and larixyl acetate or 7a,15-dihydroxydehydroabietic acid are present in significant amounts in Larix or P. sylvestris bark extracts, respectively. The identified active compounds are gained from a renewable resource potentially available in large quantities at relatively low prices, making them interesting candidates for the development of a plant derived fungicide active against a key pathogen in agriculture, providing an opportunity to the forest industry to transform low value by-products into high value-added, bioactive extracts. 2017-08-23T00:00:00Z