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Mohyeldin SM, Samy WM, Ragab D, Abdelmonsif DA, Aly RG, Elgindy NA. Int J Nanomed. 2021;16:2013–2044 The authors have advised that Figure 10A on page 2041 is incorrect owing to an inadvertent error during the preparation of representative images for Figure 10. The corrected version of Figure 10 is shown below. Figure 10 Photomicrograph of representative tissues within normal histologic limits of the brain (A,F and K), intestinal mucosa (B,G and L), gastric mucosa (C,H and M), kidney (D,I and N) and liver (E,J and O) in the negative control, blank, and SUL-LPS, respectively, ×200, H&E.Abbreviations: H&E, hematoxylin and eosin; SUL-LPS, sulpiride-loaded lipospheres. The authors sincerely apologize for this error and affirm that it does not affect the data interpretation and the conclusion of the study.

Salma M Mohyeldin,1 Wael M Samy,1 Doaa Ragab,1 Doaa A Abdelmonsif,2,3 Rania G Aly,4 Nazik A Elgindy1,5 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 3Centre of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 4Department of Surgical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 5Department of Industrial Pharmacy, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria, EgyptCorrespondence: Salma M MohyeldinDepartment of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, 1-Azarita Square, Alexandria, EgyptTel +20 1008024214Fax +20 3 4873273Email salma.eldin@alexu.edu.egBackground: Sulpiride (SUL), is a selective antidopaminergic drug that had extensive biological activities. However, its sparingly aqueous solubility and limited gastrointestinal permeability lead to scanty oral bioavailability which hinders its clinical efficacy.Objective: SUL-loaded lipospheres (SUL-LPS) were designed to serve as an oral biocompatible nanovector for improving SUL permeability as well as conquering its low oral absorption and then in turn enhancing its antidepressant action.Methods: SUL-LPS were fabricated via two processing techniques namely, melt emulsification and solvent evaporation. The impact of different lipid cores, phospholipid shells together with various surfactant concentrations and types on the lipospheres properties were screened. Detailed physicochemical elucidations were performed followed by ex vivo permeation appraisal using the non-everted intestine model. The pharmacokinetic parameters of SUL-LPS, free SUL and marketed product were assessed following oral administration to healthy rats. Reserpine-induced depression rat model was used to assess the antidepressant action of SUL-LPS on which full behavioural and biochemical analysis was conducted. Safety attributes of nanoencapsulated SUL on the brain and other internal organs were evaluated.Results: The optimum LPS revealed an excellent nanosize with a narrow PdI, negative zeta potential and acceptable entrapment efficiency of 68.62 nm, 0.242, − 30.4 mV and 84.12%, respectively. SUL-LPS showed a sustained release pattern and 2.1-fold enhancement in the intestinal permeation parameters with low mucin interaction. Oral pharmacokinetic appraisal exhibited that LPS provided 3.4-fold improvement in SUL oral bioavailability together with long-circulating properties, relative to the free drug. Pharmacodynamic study confirmed the superior antidepressant action of SUL-LPS as evident by 1.6 and 1.25-fold elevation in the serotonin and dopamine expressions, respectively. Meanwhile, nanotoxicological appraisal proved the biocompatibility of SUL-LPS upon repetitive oral administration.Conclusion: Rationally designed lipospheres hold promising in vitro and in vivo characteristics for efficient delivery of SUL with high oral bioavailability, antidepressant activity together with a good safety profile.Keywords: sulpiride, lipospheres, ex vivo permeation, bioavailability, depression, toxicity

Mohammed M Mehanna,1,2 Salma M Mohyeldin,1 Nazik A Elgindy1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, LebanonCorrespondence: Mohammed M MehannaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, P.O.Box 11 - 50 - 20 Riad El Solh, Beirut 11072809, LebanonTel +96171708661Email mmhanna@bau.edu.lbPurpose: Rifampicin, a first-line anti-tuberculosis drug, was loaded into a carbohydrate-based spray-dried nanocomposite with the aim to design a dry powder inhalation formulation. This strategy can enable efficient distribution of rifampicin within the lungs, localizing its action, enhancing its bioavailability and reducing its systemic exposure consequently side effects.Methods: The respirable nanocomposite was developed utilizing spray drying of rifampicin nanosuspension employing a combination of mannitol, maltodextrin and leucine as microparticles matrix formers. Detailed physicochemical characterization and in-vitro inhalation properties of the nanocomposite particles were investigated. Compatibility studies were carried out using differential scanning calorimetry and Infrared spectroscopy techniques. Moreover, pulmonary in-vitro cytotoxicity on alveolar basal epithelial cells was performed and evaluated.Results: Nanocomposite-based rifampicin-loaded dry inhalable powder containing maltodextrin, mannitol and leucine at a ratio of 2:1:1 was successfully formulated. Rifampicin loading efficiency into the carbohydrate nanocomposite was in the range of 89.3% to 99.2% w/w with a suitable particle size (3.47–6.80 μm) and unimodal size distribution. Inhalation efficiency of the spray-dried nanosuspension was significantly improved after transforming into an inhalable carbohydrate composite. Specifically, mannitol-based powder had higher respirable fraction (49.91%) relative to the corresponding formulation of maltodextrin. Additionally, IC50 value of rifampicin nanocomposite was statistically significantly higher than that of free drug thus providing superior safety profile on lung tissues.Conclusion: The obtained results suggested that spray drying of rifampicin nanosuspension utilizing carbohydrates as matrix formers can enhance drug inhalation performance and reduce cellular toxicity. Thus, representing an effective safer pulmonary delivery of anti-tuberculosis drugs.Keywords: carbohydrate, inhalation, nanocomposite, rifampicin, tuberculosis

Salma M Mohyeldin, Mohammed M Mehanna, Nazik A Elgindy Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Purpose: This article investigated the influence of novel rifampicin nanosuspension (RIF NS) for enhancing drug delivery properties. Methods: RIF NS was fabricated using the antisolvent precipitation technique. The impact of solvent type and flow rate, stabilizer type and concentration, and stirring time and apparatus together with the solvent–antisolvent volume ratio on its controlled nanocrystallization has been evaluated. NSs were characterized by transmission electron microscopy, particle size and zeta potential analysis, solubility, and dissolution profiles. The compatibility between RIF and the stabilizer was investigated via Fourier transform infrared spectroscopy and the differential scanning calorimetry techniques. The shelf-life stability of the RIF NS was assessed within a period of 3 months at different storage temperatures. Cell cytotoxicity was evaluated using 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on lung epithelial cells. Results: Polyvinyl alcohol at 0.4% w/v, 1:15 methanol to deionized water volume ratio and 30-minutes sonication were the optimal parameters for RIF NS preparation. Nanocrystals were obtained with a nanometeric particle size (101 nm) and a negative zeta potential (-26 mV). NS exhibited a 50-fold enhancement in RIF solubility and 97% of RIF was dissolved after 10 minutes. The RIF NS was stable at 4±0.5°C with no significant change in particle size or zeta potential. The MTT cytotoxicity assay of RIF NS demonstrated a good safety profile and reduction in cell cytotoxicity with half maximal inhibitory concentration values of 0.5 and 0.8 mg/mL for free RIF and RIF NS, respectively. Conclusion: A novel RIF NS could be followed as an approach for enhancing RIF physicochemical characteristics with a prominence of a safer and better drug delivery. Keywords: controlled nanocrystallization, cytotoxicity, nanosuspension, polyvinyl alcohol, rifampicin