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Rabab Kamel,1 Nahla A El-Wakil,2 Nermeen A Elkasabgy3 1Pharmaceutical Technology Department, National Research Centre, Cairo, Egypt; 2Cellulose and Paper Department, National Research Centre, Cairo, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, EgyptCorrespondence: Nermeen A ElkasabgyFaculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, EgyptTel +20 1141404144Email nermeen.ahmed.elkasabgy@pharma.cu.edu.eg; nermeenadelahmed@outlook.comPurpose: TEMPO-oxidized nanofibrillated cellulose (TONFC) originating from an agricultural waste (sugar cane) was utilized to prepare injectable in-situ forming hydrogel scaffolds (IHS) for regenerative medicine.Methods: TONFC was prepared and characterized for its morphology and chemical structure using TEM and FT-IR, respectively. The cold method was applied to prepare hydrogels. Various concentrations of poloxamer 407 were added to the prepared TONFC (0.5%w/w). Different sources of calcium, Fujicalin® (DCP) or hydroxyapatite (TCP), were used to formulate the aimed calcium-enriched raloxifene hydrochloride-loaded IHS. Gelation temperature, drug content, injectability and in-vitro drug release were evaluated along with the morphological characters. Cytocompatibility studies and tissue regeneration properties were assessed on Saos-2 cells.Results: TEM photograph of TONFC showed fibrous nanostructure. The selected formulation “Ca-IHS4” composed of TONFC+15% P407+10% TCP showed the most prolonged release pattern for 12 days with the least burst effect (about 25% within 24 h). SEM micro-photographs of the in-situ formed scaffolds showed a highly porous 3D structure. Cytocompatibility studies of formulation “Ca-IHS4” revealed the biocompatibility as well as improved cell adhesion, alkaline phosphatase enzyme activity and calcium ion deposition.Conclusion: The outcomes suggest that Ca-IHS4 presents a simple, safe-line and non-invasive strategy for bone regeneration.Keywords: nanofibrillated cellulose, raloxifene hydrochloride, calcium phosphate, in-situ forming hydrogel scaffolds, bone regeneration

Islam M Adel,1 Mohamed F ElMeligy,1 Mohamed EA Abdelrahim,2 Amr Maged,3,4 AbdelFattah A Abdelkhalek,5 Azza MM Abdelmoteleb,6 Nermeen A Elkasabgy1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; 2Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt; 4Pharmaceutical Factory, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt; 5Department of Microbiology of Supplementary General Science, Faculty of Oral & Dental Medicine, Future University in Egypt, Cairo, Egypt; 6Department of Chemistry, Toxicology and Feed Deficiency, Animal Health Research Institute, Agricultural Research Center, Giza, EgyptCorrespondence: Islam M AdelFaculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, EgyptTel +20 1226445511Email islam.hashim@pharma.cu.edu.egPurpose: The goal was to directly deliver curcumin, a natural polyphenolic anticancer and anti-inflammatory compound, to the lung tissues with minimal systemic exposure through the fabrication of proliposomes, overcoming its poor aqueous solubility and oral bioavailability.Methods: Nano-spray drying was employed to prepare proliposomes using hydroxypropyl beta-cyclodextrin as a carrier. Lecithin and cholesterol were used as lipids, stearylamine and Poloxamer 188 were added as positive charge inducer and a surfactant, respectively. Different characterization parameters were evaluated like percentage yield, entrapment efficiency, drug loading, aerodynamic particle size, in vitro release besides morphological examination. Cytotoxicity studies on cell line A549 lung tumor cells as well as in vivo lung pharmacokinetic studies were also carried.Results: The optimized formulations showed superior aerosolization properties coupled their enhanced ability to reach deep lung tissues with a high % of fine particle fraction. Cytotoxicity studies using MTT assay demonstrated enhanced growth inhibitory effect on lung tumor cells A549 and significant reduction of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6 and interleukin-10 compared to the pure drug. Results of lung pharmacokinetic tests confirmed the superiority of proliposomal curcumin over curcumin powder in both, the rate and extent of lung tissue absorption, as well as the mean residence time within the lung tissues.Conclusion: The pulmonary delivery of curcumin-loaded proliposomes as dry powder provides a direct approach to lung tissues targeting while avoiding the limitations of the oral route and offering a non-invasive alternative to the parenteral one.Keywords: curcumin, proliposomes, cyclodextrin, dry powder inhalers, human epithelial cell line, pulmonary delivery