Analytical Physicochemical and Functional Studies to Compare AryoTrust, a Follow-On Biologics, with the Originator Trastuzumab (Herceptin) Khalid Kadhem Al-Kinani, Hussein Kadhum Alkufi, Salam Shanta Taher Pharmaceutics, 2026 Background: Trastuzumab is a blockbuster monoclonal antibody that has revolutionized the treatment of HER2-positive breast and gastric cancers. With the increasing availability of biosimilar monoclonal antibodies in clinical practice, independent verification of biosimilarity using products sampled from a real-world supply chain is important to assure clinicians and the patients to use these products confidently. Objective: The aim of this study is to assess the biosimilarity of AryoTrust, a trastuzumab biosimilar, in comparison with the reference product Herceptin. AryoTrust and Herceptin products were randomly withdrawn from Iraqi hospitals to reflect medicines administered in real clinical settings. Methods: AryoTrust and Herceptin were compared using an extensive set of orthogonal analytical techniques which included SDS-PAGE, ion-exchange chromatography, capillary isoelectric focusing, peptide mapping, N-glycan profiling, circular dichroism, differential scanning calorimetry, and surface plasmon resonance. In addition to these teste, functional comparability was also tested using an HER2-dependent cell-based proliferation inhibition bioassay. Results: The results showed that both products have highly comparable profiles in all assessed attributes. The analysis showed similar molecular integrity and purity, identical primary structure, comparable charge heterogeneity, similar isoelectric points (pI) of the main isoform, close glycosylation patterns (mainly, by core-fucosylated complex-type glycans), similar higher-order structural features, and thermal stability. The receptor binding studies exhibited comparable binding affinities with Fcγ receptors and FcRn. Finally, the cell-based bioassay revealed comparable dose–response curves with similar EC50 values and relative potency. Conclusions: The integrated analytical and functional data support the biosimilarity of AryoTrust to the reference product Herceptin, which has been marketed and used in Iraq. This study provides real-world scientific evidence supporting confidence in the quality and comparability of this trastuzumab biosimilar and reduces any doubt in the product and at the same time emphasizes the value of independent post-marketing biosimilarity assessments.
Formulation and characterization of dolutegravir sodium-loaded nanostructured lipid carrier in situ gel for targeted brain delivery via intranasal route Salam Shanta Taher, Khalid K. Al-Kinani Opennano, 2026 Effective delivery of antiretroviral drugs to the brain is a major hurdle in treating central nervous system (CNS) HIV infections. This study developed an intranasal in situ gel containing dolutegravir sodium-loaded nanostructured lipid carriers (DTGs-NLCs) for targeted nose-to-brain delivery. DTGs-NLCs were prepared using a modified melt emulsification-ultrasonication method, yielding nanocarriers with a size of 80.8 ± 10.4 nm, zeta potential of –13±1.4 mV, and entrapment efficiency of 80.7 ± 0.48 %. These NLCs were incorporated into a thermosensitive in situ gel matrix composed of poloxamer 407 and carbopol 934P. The in vitro drug release from the gel was significantly enhanced compared to the free drug ( p < 0.05). Rheological studies confirmed the formulation’s non-Newtonian behavior, good spreadability (5.9 ± 0.13 cm), and strong mucoadhesiveness (1116.86 ± 20 dyne/cm²). Safety evaluations demonstrated excellent hemocompatibility and biocompatibility. Pharmacokinetic studies revealed that intranasal administration achieved higher brain concentrations (C max : 35.4 ± 3.6 µg/g; AUC₀–₄₈: 193.22±14.66 µg·h/g) and faster absorption (T max : 1 h) than intravenous delivery. These results indicate that the DTGs-NLC in situ gel offers a safe, non-invasive, and efficient approach for enhanced brain targeting, showing great promise for treating CNS complications of HIV, including neuroAIDS.
Current Nanotechnological Strategies for Delivery of Anti-retroviral Drugs: Overview and Future Prospects Salam Shanta Taher, Khalid Kadhem Al-kinani Current Drug Therapy, 2026 Globally, over forty million people are living with Human Immunodeficiency Viral (HIV) infections. Highly Active Antiretroviral Therapy (HAART) consists of two or three Antiretroviral (ARV) drugs and has been used for more than a decade to prolong the life of AIDS-diagnosed patients. The persistent use of HAART is essential for effectively suppressing HIV replication. Frequent use of multiple medications at relatively high dosages is a major reason for patient noncompliance and an obstacle to achieving efficient pharmacological treatment. Despite strict compliance with the HAART regimen, the eradication of HIV from the host remains unattainable. Anatomical and Intracellular viral reservoirs are responsible for persistent infection. Elimination of the virus from these reservoirs is critical for successful long-term therapy. Therefore, innovative approaches are required to design safe and effective therapies. Nanotechnology has revolutionized HIV drug delivery by addressing key challenges, including improving drug solubility, targeting specific cells, extending drug release, protecting drugs from degradation, overcoming biological barriers, enabling combination therapy, and enhancing vaccine delivery. Several nanocarrier systems, such as dendrimers, nanoemulsions, liposomes, solid nanoparticles (SLNs), and nanostructured lipid carriers, have been proposed to treat HIV infection. Additionally, nanosuspensions of antiretroviral drugs offer promising strategies for improving treatment outcomes. While these advancements have significantly improved HIV management strategies, challenges remain, including unexpected toxicity, avoiding harmful biological interactions, and costs associated with the large-scale production of nanopharmaceuticals.
In vivo Brain Pharmacokinetics of Dolutegravir Sodium-Loaded Nanostructured Lipid Carrier in situ Gel: Comparative Study with an Intravenous Drug Solution Salam Shanta Taher, Khalid Kadhem Al-Kinani Al Rafidain Journal of Medical Sciences, 2025 Background: Dolutegravir sodium (DTG), used to treat HIV, faces challenges in delivering effective therapeutic concentrations to the brain due to the blood-brain barrier (BBB). Nanostructured lipid carriers (NLCs) combined with in situ gels present a promising strategy for enhancing brain drug delivery via the intranasal route. Objective: To compare brain pharmacokinetics of DTGs delivered via NLC-loaded in situ gel intranasal administration with the conventional intravenous (IV) drug solution. Methods: 80 Wistar rats, which were divided into three groups: two groups consisting of 39 animals each and a control group with 2 animals. Rats were administered with a dose of 1.0 mg/kg of DTGs IV, and DTGs NLC-loaded in situ gel were administered intranasally. DTGs were determined in rats’ plasma and brain tissue by high-performance liquid chromatography (HPLC). Results: Intranasal administration produced significantly higher brain drug concentrations (Cmax 35344.8ng/ml) compared to the IV solution (Cmax 4536.85ng/ml). The area under the curve (AUC) for the intranasal formulation was twice that of the IV solution, indicating enhanced bioavailability. Furthermore, the intranasal route exhibited a faster onset (lower Tmax) and prolonged retention in brain tissue. The developed nanoformulation exhibited a Drug Targeting Efficiency (DTE) of 232.5% and a Drug Targeting Potential (DTP) of 57%, suggesting improved brain targeting efficiency. Conclusions: The DTGs-loaded NLC in situ gel shows superior brain pharmacokinetics compared to IV administration, highlighting its potential as an effective strategy for enhancing brain targeting.
Response surface optimization and in vitro study of nasal solusomes nanovesicles for the bioavailability improvement and brain targetting of sumatriptan , Ahmed H Salman Salman, Hussein K. Alkufi Alkufi, , Salam Shanta Taher Taher, , Sumayah Al-Mahmood Al-Mahmood, , Mahmood A. Haiss Haiss, and Epitheorese Klinikes Farmakologias Kai Farmakokinetikes, 2024 Background: One effective second-generation triptan for migraine attacks is sumatriptan. Following oral use, it has a 40% restricted bioavailability because of the first-pass metabolism. Aim: To develop the best intranasal Solusomes formula as a substitute that delivers into the brain directly, improving its bioavailability, and removing the first-pass outcome was the aim of this effort. Methodology: We developed solute formulations based on the Box-Behnken design and subsequently produced them via thin-film hydration. The quality by design technique was used to establish a correlation between the formulation parameters (Soluplus® and phosphatidylcholine (PC) concentrations) and signif¬icant quality powers (entrapment efficiency (EE%), vesicle size (VS), and polydispersity index (PDI)). Fourier trans¬form infrared spectroscopy (FTIR), optical microscopy, and an in vitro diffusion study were performed on the revised formula. Results: The enhanced formulation exhibited a VS of 93.76 nm, an EE% of 83.65%, and PDI 0.3362 with the least amount of error between the projected and observed values. Conclusion: This study offered a feasible and efficient intranasal formulation appropriate for further brain delivery research.
Effect of Food on the Pharmacokinetics of Fluoxetine in Healthy Male Adult Volunteers Duaa J. Al-Tamimi, Khalid Kadhem Al-Kinani, Salam Shanta Taher, Ahmed A. Hussein Iraqi Journal of Pharmaceutical Sciences, 2022 Fluoxetine (FX) is an antidepressant drug administered only orally in humans. Despite the wide use of FX, until now, there is only limited literature concerning the pharmacokinetics (PK) of FX and the effect of food on its PK. Thus, the objective of this investigation was to study the PK of FX in Arabic healthy male adult volunteers under fasting and fed conditions. In the fasting study, FX 20 mg capsules (Prozac®, Eli Lilly, Canada) were administered to 41 volunteers after overnight fasting of 12 hours, followed by blood sampling from each volunteer immediately before dosing (zero time) and then at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 60, 72, 96, 120, and eventually at 144 hours after FX dosing. The fed study was conducted after 90 days wash-out period following the completion of the fasting study. The same subjects who received FX in the fasting study were administered the drug directly after a fatty breakfast (fed study), followed by blood sampling intervals similar to the schedule mentioned above for the fasting study. The current investigation demonstrated no statistical differences in the FX pharmacokinetic parameters Cmax, AUC0–t, AUC0–∞, Kel, T1/2, MRT, Cl/F, and Vd/F after fasting compared to the fed conditions, whereas there was statistically significant elongation in the Tmax values after food intake. Therefore, this study concludes the absence of food effect on the PK of FX (except Tmax) in the Arabic population and confirms the method of administration mentioned in the product information but also concludes high interindividual variation in FX exposure (AUC), which suggest that therapeutic drug monitoring (TDM) might be advisable when feasible.
Co-surfactant effect of polyethylene glycol 400 on microemulsion using BCS class II model drug Salam Shanta Taher, Khalid Kadhem Al-Kinani, Zahraa Mohsen Hammoudi, Mowafaq mohammed Ghareeb Journal of Advanced Pharmacy Education and Research, 2022 Microemulsions are an intriguing method for delivering poorly soluble drugs, protecting labile drugs, controlling drug release, and increasing drug bioavailability. They can be given topically, orally, or intravenously, and use polyethylene glycol (PEG-400) as a cosurfactant to improve the solubility and stability of biological classification system (BCS) class II drugs. The goal of this research is to develop and test an oil-in-water (O/W) microemulsion-based formulation to improve the solubility and possibly the stability of a hydrophobic medication (carvedilol) by using natural oil and PEG 400 as a co-surfactant. oil in water microemulsion was formulated using the water titration method. pH, particle size, zeta potential, and thermodynamic stability studies were carried out for optimization, followed by in vitro release experiments. Based on component solubility studies and pseudo-ternary phase diagrams, a 1:1 ratio of Tween80 to PEG400 (Smix) was chosen for the final microemulsion preparation. The optimized ME4 formula selected contains 10% oil, 42% Smix, and 48% water. The average globule size was found to be 58 nm, the pH was 6.95, the zeta potential was 28mV, and the percent transmittance was 97.1 percent. The thermodynamic stability study data shows better stability of the final formulation. The solubilization effect of the drug was enhanced by prepared ME formulation and hence confirms the utility of the ME system as a vehicle for better delivery of (BCS) class II.
SOLID LIPID NANOPARTICLES AS A PROMISING APPROACH FOR DELIVERY OF ANTICANCER AGENTS: REVIEW ARTICLE Salam Shanta Taher, Zainab Ahmed Sadeq, Khalid Kadhem Al-Kinani, Zahraa Salim Alwan Military Medical Science Letters Vojenske Zdravotnicke Listy, 2022 Cancer disease has a complicated pathophysiology and is one of the major causes of death and morbidity. Classical cancer therapies include chemotherapy, radiation therapy, and immunotherapy. A typical treatment is chemotherapy, which delivers cytotoxic medications to patients to suppress the uncontrolled growth of cancerous cells. Conventional oral medication has a number of drawbacks, including a lack of selectivity, cytotoxicity, and multi-drug resistance, all of which offer significant obstacles to effective cancer treatment. Multidrug resistance (MDR) remains a major challenge for effective cancer chemotherapeutic interventions. The advent of nanotechnology approach has developed the field of tumor diagnosis and treatment. Cancer nanotechnology enables direct access to tumor cells, resulting in enhanced drug localization and cellular uptake. Since the early 1990’s, several solid lipid nanoparticle (SLN) or SLN-based systems for the delivery of cytotoxic drugs have been manufactured and tested with success. High shear homogenization, microemulsionbased SLN, Supercritical fluid technology, spray drying, and solvent emulsification/evaporation methods can all be used to successfully formulate SLN.There is great potential to enhance cancer chemotherapy by incorporating it into a solid lipid nanoparticle (SLN) drug delivery system. Improving tumor diffusivity, improvement of body distribution, and inhibiting MDR are the main attributes. This type of review article discusses advantages and disadvantages of SLNs, their production techniques, and their potential usage in the treatment of various cancers.
