Dereje Kebebe - Academia.edu (original) (raw)

Papers by Dereje Kebebe

Journal of Herbal Medicine, Aug 1, 2023

Journal of Aerosol Medicine and Pulmonary Drug Delivery, Apr 1, 2020

Background: Salvia miltiorrhiza polyphenolic acid (SMPA) is effective in the treatment of cardiov... more Background: Salvia miltiorrhiza polyphenolic acid (SMPA) is effective in the treatment of cardiovascular diseases and currently it is administered orally or intravenously. However, SMPA is poorly absorbed orally and quickly eliminated in vivo. A long-term frequent intravenous administration leads to poor patient compliance. Therefore, it is urgently demanded to find a new alternative route of noninjection drug delivery system for SMPA. Methods: Two dry powder inhalation (DPI) formulations of spray-dried SMPA formulation (P1) and spray-dried SMPA-L-leucine formulation (P2) were prepared by spray drying method and their physicochemical properties were assessed by thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, particle size distribution analysis, and in vitro aerodynamic analysis. Moreover, In vitro cytotoxicity of SMPA and P2 was conducted with NR8383 cells. In vivo pharmacokinetics were carried out by Penn-Century endotracheal intubation technique to deliver P2 to the lungs of rats. Results and Conclusions: The moisture content of P1 and P2 were 5.81% ± 0.005%, and 4.08% ± 0.002%, respectively. P1 and P2 were in an amorphous state. Moreover, P1 had slightly corrugated surfaces, whereas P2 exhibited severely corrugated surfaces with invagination due to the presence of L-leucine. In addition, there were more hollow particles with smooth surface in P1 than that in P2. Compared with P1, P2 has shown optimal physical particle size and aerosolization behavior with D (v, 50) of 2.64 ± 0.01 μm and fine particle fraction of 37.55% ± 2.63%. The findings of in vitro cytotoxicity showed that P2 did not inhibit cell viability and could be safe for pulmonary administration. The absolute bioavailability of salvianolic acid B (Sal B) for pulmonary administration was 19.15% ± 7.44%, which is significantly higher than the oral bioavailability of Sal B (<5.56%). In this study, we have shown the feasibleness of pulmonary administration of SMPA in the form of DPIs for systemic delivery to treat cardiovascular diseases.

Journal of experimental pharmacology, Feb 1, 2023

The emergence and spread of resistant microbes continue to be a major public health concern. Effe... more The emergence and spread of resistant microbes continue to be a major public health concern. Effective treatment alternatives, particularly from traditionally used medicinal plants, are needed. Objective: The main objective of this study was to conduct phytochemical screening and antimicrobial activity evaluation of selected traditionally used medicinal plants in Ethiopia. Methods: The ethnomedicinal use value frequency index (FI) was used to select twelve medicinal plants. Phytochemical classes of compounds were screened using different standard methods. Anti-microbial activities of plant extracts were evaluated against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Candida albicans. Minimum inhibitory concentrations were measured using the broth micro-dilution method. The data were analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0 and the findings were presented descriptively and using non parametric one-way ANOVA analysis (Kruskal-Wallis/Ddunn's test). Results: The phytochemical constituents identified were flavonoids, alkaloids, glycosides, phenols, saponins, steroids, and terpenoids, with flavonoids, alkaloids, and phenols being the most abundant. The crude extracts and chloroform fractions of the extracts showed an activity against the tested strains. The crude extract of Thalictrum rhynchocarpum Quart.-Dill. and A.Rich root demonstrated superior activity against all the tested strains with the lowest minimum inhibitory concentrations of 0.48 μg/mL against Staphylococcus aureus and Escherichia coli; 0.98 μg/mL against Klebsiella pneumoniae, Pseudomonas aeruginosa; and 3.90 μg/mL against Candida albicans, which are even better than the reference drug, gentamicin and clotrimazole. Conclusion: The majority of evaluated medicinal plants demonstrated remarkable activity against tested microbial strains, which can be attributed to the presence of secondary metabolites of different classes of compounds. The finding provided scientific evidence for the use of these traditionally used medicinal plants.

Ethiopian Pharmaceutical Journal, Jul 24, 2012

Olibanum is an oleo-gum resin which is economically and culturally valuable product obtained from... more Olibanum is an oleo-gum resin which is economically and culturally valuable product obtained from several species of the genus Boswellia. In this study, the resins extracted from local olibanum: Boswellia papyrifera (Tigray type) and Boswellia rivae (Ogaden type) were evaluated as matrix forming agents in sustained release tablet formulations employing diclofenac sodium as a model drug. Some physico-chemical characterization of the resins revealed low solubility, moisture content and swelling ratio. Sustained release matrix tablets containing 100 mg of diclofenac sodium were then prepared using different proportions of the olibanum resins by wet granulation and direct compression methods, and evaluated for their pharmacotechnical properties and in vitro drug release kinetics. Both resins produced matrix tablets with acceptable weight variation, hardness and friability. Dissolution studies showed that the olibanum resins sustain the drug release beyond 12 h. Drug release from the olibanum resins matrix tablets were best fitted to the Korsmeyer-Peppas model with the mechanism of drug release generally following non-Fickian diffusion process. Diclofenac release profiles from some of the formulated tablets were comparable to that of the commercial sustained release tablet Diclo-Denk® Retard. Keywords: Olibanum resin, matrix tablet, diclofenac sodium, sustained release, release kinetics

Journal of Nanobiotechnology, Aug 23, 2021

Although nanomedicine have greatly developed and human life span has been extended, we have witne... more Although nanomedicine have greatly developed and human life span has been extended, we have witnessed the soared incidence of central nervous system (CNS) diseases including neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), ischemic stroke, and brain tumors, which have severely damaged the quality of life and greatly increased the economic and social burdens. Moreover, partial small molecule drugs and almost all large molecule drugs (such as recombinant protein, therapeutic antibody, and nucleic acid) cannot cross the blood-brain barrier. Therefore, it is especially important to develop a drug delivery system that can effectively deliver therapeutic drugs to the central nervous system for the treatment of central nervous system diseases. Cell penetrating peptides (CPPs) provide a potential strategy for the transport of macromolecules through the blood-brain barrier. This study analyzed and summarized the progress of CPPs in CNS diseases from three aspects: CPPs, the conjugates of CPPs and drug, and CPPs modified nanoparticles to provide scientific basis for the application of CPPs for CNS diseases.

Journal of Experimental Pharmacology

Evidence-Based Complementary and Alternative Medicine

Fructus Gleditsiae Abnormalis (FGA) has been used as a traditional Chinese medicine (TCM) for the... more Fructus Gleditsiae Abnormalis (FGA) has been used as a traditional Chinese medicine (TCM) for the treatment of stroke caused by phlegm and blood stasis. However, its substance basis and mechanism of action are currently unknown. This study is aimed to analyze the constituents of the volatile oil in FGA (VOFGA) using gas chromatography coupled with mass spectrometry (GC-MS) and explore the underlying effects and mechanisms of VOFGA in the prevention and treatment of ischemia stroke. An in vivo ischemia model was constructed by combination treatment of high-fat diet (HFD) and middle cerebral artery occlusion (MCAO) method. After administration, the cerebral infarction volume, the brain water content, hemorheology, blood lipids, inflammatory factors, oxidative stress indicators, Bax, Bcl-2, and cleaved caspase-3 and histological examination (HE) were determined and observed to explore the underlying effects and mechanisms of VOFGA against ischemia stroke. The results showed that forty ...

BMC Health Services Research

Background Pharmaceutical compounding ensures access of individuals with specific requirements to... more Background Pharmaceutical compounding ensures access of individuals with specific requirements to individualized therapy. However, there is an inconsistency of compounded medication quality. Therefore, advancing the rational use of compounded medication is essential for patient safety and medication effectiveness. Objective The presented study was aimed to investigate the healthcare practitioners’ knowledge, perception, and practice of extemporaneous compounding and its contribution to the prevalence of antimicrobial resistance. Method A descriptive cross-sectional survey using a structured questionnaire was conducted. The study participants were 300 healthcare practitioners working in Jimma University Medical Center, hospital pharmacies, and community pharmacies in Jimma and Mettu Town, Southwest Ethiopia. Results Most respondents were pharmacists (62.7%) and first-degree holders (48.3%). The majority of them had experience in administering (57.7%), preparing (38%), prescribing (21...

Acupuncture and Herbal Medicine, 2021

Supplemental Digital Content is available in the text Abstract Objective: This study aimed to lay... more Supplemental Digital Content is available in the text Abstract Objective: This study aimed to lay the foundation for the research on Panax notoginseng saponins (PNS) in pH-sensitive in situ gel and the development and improvement of related preparations. Methods: We used Carbopol®940, a commonly used pH-sensitive polymer, and the thickener hydroxypropyl methylcellulose (HPMC E4M) as an ophthalmic gel matrix to prepare an ophthalmic in situ gel of PNS. In addition, formula optimization was performed by assessing gelling capability with the results of in vitro release studies. In vitro (corneal permeation, rheological, and stability) and in vivo (ocular irritation and preliminary pharmacokinetics in the vitreous) studies were also performed. Results: The results demonstrated that the in situ gelling systems containing PNS showed a sustained release of the drug, making it an ideal ocular delivery system for improving posterior ocular bioavailability. Conclusions: This study lays the foundation for the research of PNS contained in an in situ pH-triggered gel as well as the development and improvement of related preparations. It concurrently traditional Chinese medicine with a contemporary in situ gelling approach to provide new directions for the treatment of posterior ocular diseases such as diabetic retinopathy.

Additional file 1. The descriptions, formula, interpretation, and data sources of the main indica... more Additional file 1. The descriptions, formula, interpretation, and data sources of the main indicators/variables used in the current study.

Blindness and vision impairment are the most devastating global health problems resulting in a su... more Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden. Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system. Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability (< 5%). The designing of a novel approach for a safe, simple, and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem. Over the past decades, several novel approaches involving different strategies have been developed to improve the ocular delivery system. Among these, the ophthalmic in-situ gel has attained a great attention over the past few years. This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.

Efavirenz, a widely prescribed HIV-1 specific non-n ucleoside reverse transcriptase inhibitor [An... more Efavirenz, a widely prescribed HIV-1 specific non-n ucleoside reverse transcriptase inhibitor [Anti-ret roviral drug] belongs to Class II under BCS and exhibit low and v ariable oral bioavailability due to its poor aqueou s solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and diss olution rate for increasing oral bioavailability. The objective of t he study is to evaluate the dissolution rate of for mulated Efavirenz tablets in different dissolution media. A Comparati ve evaluation was made for the dissolution of prepa red tablets in 1% SLS,2 % SLS, Phosphate buffer PH 7.4. The tablet s were evaluated for dissolution rate and other phy sical properties. Efavirenz dissolution was rapid and hig her in 2% SLS when compared to Phosphate buffer and 1% SLS. Among the three media, 2% SLS gave highest enhancem ent in the dissolution rate and dissolution efficiency of Efavirenz tablets.

Journal of Pharmaceutical Policy and Practice, 2020

Background Maintaining an efficient and effective inventory management system ensures a reliable ... more Background Maintaining an efficient and effective inventory management system ensures a reliable supply of laboratory commodities. The aim of this study was, therefore, to assess the performance of inventory management for laboratory commodities in public hospitals in the Jimma zone. Methods A facility-based cross-sectional descriptive study, accompanied by a qualitative method, was conducted in seven public hospitals between April 30 and May 29, 2019. We collected data through document reviews (225 bin-cards), physical observation, self-administered questionnaires, and in-depth interviews. The quantitative data were analyzed using Excel spreadsheets and SPSS version 24. Fifteen key informants of different backgrounds took part in the qualitative study. The data were then analyzed using thematic analysis techniques. Results All the public hospitals in the zone were included in the study, making a response rate of 100%. Of the total estimated bin-cards, 225 (69.9%) of them held along...

Mini-Reviews in Medicinal Chemistry, 2020

Pulmonary pharmaceutical formulations are targeted for the treatment of respiratory diseases. How... more Pulmonary pharmaceutical formulations are targeted for the treatment of respiratory diseases. However, their application is limited due to the physiological characteristics of the lungs, such as branching structure, mucociliary and macrophages, as well as certain properties of the drugs like particle size and solubility. Nano-formulations can ameliorate particle sizes and improve drug solubility to enhance bioavailability in the lungs. The nano-formulations for lungs reviewed in this article can be classified into nanocarriers, no-carrier-added nanosuspensions and polymer-drug conjugates. Compared with conventional inhalation preparations, these novel pulmonary pharmaceutical formulations have their own advantages, such as increasing drug solubility for better absorption and less inflammatory reaction caused by the aggregation of insoluble drugs; prolonging pulmonary retention time and reducing drug clearance; improving the patient compliance by avoiding multiple repeated administra...

Journal of Parasitology Research, 2017

Background. Currently, antimalarial drug resistance poses a serious challenge. This stresses the ... more Background. Currently, antimalarial drug resistance poses a serious challenge. This stresses the need for newer antimalarial compounds. Carica papaya is used traditionally and showed in vitro antimalarial activity. This study attempted to evaluate in vivo antimalarial activity of C. papaya in mice. Methods. In vivo antimalarial activity of solvent fractions of the plant was carried out against early P. berghei infection in mice. Parasitemia, temperature, PCV, and body weight of mice were recorded. Windows SPSS version 16 (one-way ANOVA followed by Tukey’s post hoc test) was used for data analysis. Results. The pet ether and chloroform fractions of C. papaya fruit rind and root produced a significant (p<0.001) chemosuppressive effect. A maximum parasite suppression of 61.78% was produced by pet ether fraction of C. papaya fruit rind in the highest dose (400 mg/kg/day). Only 400 mg/kg/day dose of chloroform fraction of C. papaya root exhibited a parasite suppression effect (48.11%)...

Chinese Herbal Medicines, 2018

Objective A selective and sensitive ultra performance liquid chromatography-tandem mass spectrome... more Objective A selective and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was employed to study the pharmacokinetics of ginsenoside Re (GRe) in rabbits after vaginal administration of Xiaomi suppository to evaluate the systemic exposure of the suppository for the local treatment. Methods Chromatographic separation was on an ACQUITY UPLC ® BEH C 18 column, and acetonitrile-0.1% formic acid was used as mobile phase in gradient elution. The plasma samples were deproteinized by acetonitrile, and the pharmacokinetic parameters were calculated by Winnonlin 6.4. Results Calibration curve of GRe showed a good linearity over the concentration range from 5 ng/mL to 500 ng/mL (r = 0.9999). The low limit of quantification of 5 ng/mL could satisfy the experimental requirement. The intra-day and inter-day precision of GRe at three concentrations were less than 1.96%, and the average recoveries of GRe were >64.0%. The pharmacokinetic parameters for vaginal administration were as follows: T max , 0.5 h; C max , 20.88 ng/mL; AUC 0-t , 64.71 h•ng/mL and the residence time was 3.06 h. By using deconvolution calculation method, the cumulative absorption fraction of GRe was about 0.89%. Conclusion The systemic exposure of GRe was precious little after the vaginal administration of Xiaomi suppository.

International Journal of Pharmaceutics, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

International Journal of Nanomedicine, 2019

Background and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi... more Background and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cellspecific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK) 2 ]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity. Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice. Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1 H-NMR spectra confirmed the successful conjugation of the peptides with the NLC. The in-vitro cytotoxicity study on 4T1 cells revealed that c(RGD) peptides modified GA-NLCs showed significantly higher cytotoxicity at 0.25 and 0.5 µg/mL as compared to unmodified GA-NLC. Furthermore, the cell uptake study demonstrated that better accumulation of E-[c(RGDfK) 2 ] peptides modified NLC in 4T1 cell after 12 h incubation. Moreover, the in-vivo study showed that c(RGD)s functionalized GA-NLC exhibited better accumulation in tumor tissue and tumor growth inhibition. In contrast to the monomeric c(RGD) peptide, the dimeric c(RGD) peptide (E-[c (RGDfK) 2 ]) conjugated GA-NLC showed the improved antitumor activity and tumor targeting ability of GA-NLC. Conclusion: These data provide further support for the potential clinical applications of E-[c (RGDfK) 2 ]-GA-NLC in breast cancer therapy.

Biomedicine & Pharmacotherapy, 2019

Liver diseases are clinically common and present a substantial public health issue. Many of the c... more Liver diseases are clinically common and present a substantial public health issue. Many of the currently available drugs for the treatment of liver diseases suffer from limitations that include low hepatic distribution, lack of target effects, poor in vivo stability and adverse effects on other organs. Consequently, conventional treatment of hepatic diseases is ineffective. TCM is commonly used in the treatment of liver diseases worldwide, particularly in China, and has advantages over conventional therapy. HTDDS can be designed to enhance clinical efficacy in the treatment of liver diseases. We have conducted an extensive review of 335 studies reported since 1964. These included about 166 references involving the treatment of liver diseases with TCM (covering active components of TCM, single TCM and Chinese medicine formulas), 169 reports on HTDDS and background studies on liver-related diseases. Here we review the long history of TCM in the treatment of liver diseases.We have also reviewed the status of studies on active components of TCM using nanotechnology-based targeted delivery systems to provide support for further research and development of TCM-based targeted preparations for the treatment of liver disease.