Yousry, C., M. Goyal, and V. Gupta, "Excipients for Novel Inhaled Dosage Forms: An Overview.", AAPS PharmSciTech, vol. 25, issue 2, pp. 36, 2024. Abstract

Pulmonary drug delivery is a form of local targeting to the lungs in patients with respiratory disorders like cystic fibrosis, pulmonary arterial hypertension (PAH), asthma, chronic pulmonary infections, and lung cancer. In addition, noninvasive pulmonary delivery also presents an attractive alternative to systemically administered therapeutics, not only for localized respiratory disorders but also for systemic absorption. Pulmonary delivery offers the advantages of a relatively low dose, low incidence of systemic side effects, and rapid onset of action for some drugs compared to other systemic administration routes. While promising, inhaled delivery of therapeutics is often complex owing to factors encompassing mechanical barriers, chemical barriers, selection of inhalation device, and limited choice of dosage form excipients. There are very few excipients that are approved by the FDA for use in developing inhaled drug products. Depending upon the dosage form, and inhalation devices such as pMDIs, DPIs, and nebulizers, different excipients can be used to provide physical and chemical stability and to deliver the dose efficiently to the lungs. This review article focuses on discussing a variety of excipients that have been used in novel inhaled dosage forms as well as inhalation devices.

Ammar, H. O., R. N. Shamma, C. Yousry, and R. S. Elbatanony, "Characterization, cellular uptake in Caco-2 cells and physiologically based pharmacokinetic modeling of baicalin-loaded solid lipid nanoparticles", Future Journal of Pharmaceutical Sciences, vol. 9, pp. 61, 2023.
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rofida albash, C. Yousry, A. M. Al-mahallawi, and A. A. Alaa-Eldin, "Utilization of PEGylated cerosomes for effective topical delivery of fenticonazole nitrate: characterization, statistical optimization, and assessment.", Drug delivery, vol. 28, issue 1, pp. 1-9, 2021. Abstractutilization_of_pegylated_cerosomes_for_effective_topical_delivery_of_fenticonazole_nitrate_in_vitro_characterization_statistical_optimization_and_in.pdf

In this investigation, we focused on ceramide IIIB, a skin component whose depletion tends to augment multiple skin disorders and fungal infections. Ceramide IIIB was included into PEGylated surfactant-based vesicular phospholipid system to formulate 'PEGylated cerosomes' (PCs) loaded with fenticonazole nitrate (FTN). FTN is a potent antifungal agent adopted in the treatment of mixed mycotic and bacterial infections. The ceramide content of the vesicles may provide protective and regenerative skin activity whereas Brij; the PEGylated surfactant, can enhance drug deposition and skin hydration. Both components are expected to augment the topical effect of FTN. PCs were prepared by thin-film hydration technique. A 2 full-factorial design was applied to study the effect of ceramide amount (X), Brij type (X) and Brij amount (X) on the physicochemical properties of the formulated PCs namely; entrapment efficiency (EE%;Y), particle size (PS;Y), polydispersity index (PDI;Y) and zeta potential (ZP;Y). The optimal formula was selected for further dermatokinetic and histopathological study. The optimal FTN-loaded PC (PC6) showed nanosized cerosomes (551.60 nm) with high EE% (83.00%w/w), and an acceptable ZP value of 20.90 mV. Transmission electron micrographs of the optimal formula illustrated intertwined tubulation form deviated from the conventional spherical vesicles. Finally, the dermatokinetic study of PC6 showed higher drug concentration and localization of FTN in skin layers when compared with FTN suspension and the histopathological study confirmed its safety for topical application. The overall findings of our study verified the effectiveness of utilizing PEGylated cerosomes to augment the activity of FTN as a topical antifungal agent.

Chauhan, G., X. Wang, C. Yousry, and V. Gupta, "Scalable Production and In Vitro Efficacy of Inhaled Erlotinib Nanoemulsion for Enhanced Efficacy in Non-Small Cell Lung Cancer (NSCLC).", Pharmaceutics, vol. 15, issue 3, 2023. Abstractpharmaceutics-15-00996.pdf

Non-small cell lung cancer (NSCLC) is a global concern as one of the leading causes of cancer deaths. The treatment options for NSCLC are limited to systemic chemotherapy, administered either orally or intravenously, with no local chemotherapies to target NSCLC. In this study, we have prepared nanoemulsions of tyrosine kinase inhibitor (TKI), erlotinib, using the single step, continuous manufacturing, and easily scalable hot melt extrusion (HME) technique without additional size reduction step. The formulated nanoemulsions were optimized and evaluated for their physiochemical properties, in vitro aerosol deposition behavior, and therapeutic activity against NSCLC cell lines both in vitro and ex vivo. The optimized nanoemulsion showed suitable aerosolization characteristics for deep lung deposition. The in vitro anti-cancer activity was tested against the NSCLC A549 cell line which exhibited 2.8-fold lower IC for erlotinib-loaded nanoemulsion, as compared to erlotinib-free solution. Furthermore, ex vivo studies using a 3D spheroid model also revealed higher efficacy of erlotinib-loaded nanoemulsion against NSCLC. Hence, inhalable nanoemulsion can be considered as a potential therapeutic approach for the local lung delivery of erlotinib to NSCLC.

Fathi, H. A., C. Yousry, M. Elsabahy, Mahmoud El-Badry, and O. N. Elgazayerly, "Effective Loading of Incompatible Drugs into Nanosized Vesicles: A Strategy to Allow Concurrent Administration of Furosemide and Midazolam in Simulated Clinical Settings.", International journal of pharmaceutics, vol. 636, pp. 122852, 2023. Abstract

The current study aims to assess the use of nanocarriers to limit drug incompatibilities in clinical settings, and thus eliminating serious clinical consequences (e.g., catheter obstruction and embolism), and enhancing in vivo bioavailability and efficacy. As a proof-of-concept, the impact of loading well-documented physically incompatible drugs (i.e., furosemide and midazolam) into nanosized vesicles on in vitro stability and in vivo bioavailability of the two drugs was investigated. Furosemide and midazolam were loaded into nanosized spherical vesicles at high entrapment efficiency (ca. 62-69%). The drug-loaded vesicles demonstrated a sustained drug release patterns, high physical stability and negligible hemolytic activity. Physical incompatibility was assessed by exploiting microscopic technique coupled with image processing and analysis, dynamic light scattering and laser Doppler anemometry. Incorporation of drugs separately inside the nanosized vesicles dramatically decreased size and number of the precipitated particles. In vivo, the niosomal drug mixture demonstrated a significant improvement in pharmacokinetic profiles of furosemide and midazolam compared to the mixed free drug solutions, as evidenced by their longer circulation half-lives and higher area under the plasma-concentration time curves of both drugs. Nanocarriers could provide an auspicious strategy for circumventing drug incompatibilities, thus reducing adverse reactions, hospitalization period and improving therapeutic outcomes.

Ali, M. M., R. A. Shoukri, and C. Yousry, "Thin film hydration versus modified spraying technique to fabricate intranasal spanlastic nanovesicles for rasagiline mesylate brain delivery: Characterization, statistical optimization, and in vivo pharmacokinetic evaluation.", Drug delivery and translational research, vol. 13, issue 4, pp. 1153-1168, 2023. Abstracttfh_vs_mst_ddtr.pdf

Rasagiline mesylate (RM) is a monoamine oxidase inhibitor that is commonly used to alleviate the symptoms of Parkinson's disease. However, it suffers from low oral bioavailability due to its extensive hepatic metabolism in addition to its hydrophilic nature which limits its ability to pass through the blood-brain barrier (BBB) and reach the central nervous system where it exerts its pharmacological effect. Thus, this study aims to form RM-loaded spanlastic vesicles for intranasal (IN) administration to overcome its hepatic metabolism and permit its direct delivery to the brain. RM-loaded spanlastics were prepared using thin film hydration (TFH) and modified spraying technique (MST). A 2 factorial design was constructed to study and optimize the effects of the independent formulation variables, namely, Span type, Span: Brij 35 ratio, and sonication time on the vesicles᾽ characteristics in each preparation technique. The optimized system prepared using MST (MST 2) has shown higher desirability factor with smaller PS and higher EE%; thus, it was selected for further in vivo evaluation where it revealed that the extent of RM distribution from the intranasally administered spanlastics to the brain was comparable to that of the IV drug solution with significantly high brain-targeting efficiency (458.47%). These results suggest that the IN administration of the optimized RM-loaded spanlastics could be a promising, non-invasive alternative for the efficient delivery of RM to brain tissues to exert its pharmacological activities without being dissipated to other body organs which subsequently may result in higher pharmacological efficiency and better safety profile.

Yousry, C., N. S. Farrag, and A. M. Amin, "Radiolabeling of statistically optimized nanosized atorvastatin suspension for liver targeting and extensive imaging of hepatocellular carcinoma", Journal of drug delivery science and technology, vol. 80, pp. 104171, 2023.
Yousry, C., M. M. Saber, and W. H. Abd-Elsalam, "A Cosmeceutical Topical Water-in-Oil Nanoemulsion of Natural Bioactives: Design of Experiment, in vitro Characterization, and in vivo Skin Performance Against UVB Irradiation-Induced Skin Damages.", International journal of nanomedicine, vol. 17, pp. 2995-3012, 2022. Abstract

Introduction: Damage to human skin occurs either chronologically or through repetitive exposure to ultraviolet (UV) radiation, where collagen photodegradation leads to the formation of wrinkles and skin imperfections. Consequently, cosmeceutical products containing natural bioactives to restore or regenerate collagen have gained a remarkable attention as an ameliorative remedy.

Methods: This study aimed to develop and optimize collagen-loaded water-in-oil nanoemulsion (W/O NE) through a D-optimal mixture design to achieve an ideal multifunctional nanosystem containing active constituents. Vit E was included as a constituent of the formulation for its antioxidant properties to minimize the destructive impact of UV radiation. The formulated systems were characterized in terms of their globule size, optical clarity, and viscosity. An optimized system was selected and evaluated for its physical stability, in vitro wound healing properties, and in vivo permeation and protection against UV radiation. In addition, the effect of collagen-loaded NE was compared to Vit C-loaded NE and collagen-/Vit C-loaded NEs mixture as Vit C is known to enhance collagen production within the skin.

Results: The optimized NE was formulated with 25% oils (Vit E: safflower oil, 1:3), 54.635% surfactant/cosurfactant (Span 80: Kolliphor EL: Arlasolve, 1:1:1), and 20.365% water. The optimized NE loaded with either collagen or Vit C exhibited a skin-friendly appearance with boosted permeability, and improved cell viability and wound healing properties on fibroblast cell lines. Moreover, the in vivo study and histopathological investigations confirmed the efficacy of the developed system to protect the skin against UV damage. The results revealed that the effect of collagen-/Vit C-loaded NEs mixture was more pronounced, as both drugs reduced the skin damage to an extent that it was free from any detectable alterations.

Conclusion: NE formulated using Vit E and containing collagen and/or Vit C could be a promising ameliorative remedy for skin protection against UVB irradiation.

Farag, D. B. E., C. Yousry, A. M. Al-mahallawi, H. I. El-Askary, M. R. Meselhy, and N. AbuBakr, "The efficacy of Origanum majorana nanocubosomal systems in ameliorating submandibular salivary gland alterations in streptozotocin-induced diabetic rats", Drug delivery, vol. 29, issue 1, pp. 62-74, 2022. origanum_majorana.pdf
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