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1.
Saudi Pharm J ; 32(6): 102063, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38650911

RESUMO

Purpose: Isotretinoin (ITN) is a poorly water-soluble drug. The objective of this study was to design a successful liquid self-nanoemulsifying drug delivery system (L-SNEDDS) for ITN to improve its solubility, dissolution rate, and antibacterial activity. Methods: According to solubility and emulsification studies, castor oil, Cremophor EL, and Transcutol HP were selected as system excipients. A pseudo ternary phase diagram was constructed to reveal the self-emulsification area. The developed SNEDDS were visually assessed, and the droplet size was measured. In vitro release studies and stability studies were conducted. The antimicrobial effectiveness against multiple bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and different accessory gene regulator (Agr) variants were investigated for the optimum ITN-loaded SNEDDS formulation. Results: Characterization studies showed emulsion homogeneity and stability (%T 95.40-99.20, A graded) with low droplet sizes (31.87 ± 1.23 nm-115.47 ± 0.36 nm). It was found that the developed ITN-SNEDDS provided significantly a higher release rate (>96 % in 1 h) as compared to the raw drug (<10 % in 1 h). The in vitro antimicrobial activities of pure ITN and ITN-loaded SNEDDS demonstrated a remarkable inhibitory effect on bacterial growth with statistically significant findings (p < 0.0001) for all tested strains when treated with ITN-SNEDDS as compared to the raw drug. Conclusion: These outcomes suggested that SNEDDS could be a potential approach for improving solubility, dissolution rates, and antibacterial activity of ITN.

2.
J Infect Public Health ; 17(2): 372-377, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38217931

RESUMO

BACKGROUND: Long-term effects of COVID-19 showed a wide range of symptoms. Also, it was found that older patients were five times more likely than younger patients to develop long-COVID symptoms (1). This study aimed to investigate the use of Nutrition Risk Screening 2002 (NRS-2002) and the Mini Nutrition Assessment-Short Form (MNA-sf) among COVID-19 in elderly patients in Saudi Arabia. METHODS: A total of (n = 159) COVID-19 elderly patients were recruited in the study; the relationship between patients' characteristics, including age, gender, Body Mass Index (BMI), infection history, vaccination and chronic disease were evaluated using NRS-2002 and MNA-sf. Multivariate logistic regression to estimate the Odd Ratio (OR) by comparing the OR of different variables between normal nutritional Status and at-risk and Cohen's kappa (κ) coefficient was assessed to analyse the agreement between both tools. RESULTS: MNA-sf showed a positive association between age and malnutrition risk ≥ 66 years old P = 0.035. Both tools showed a negative association between BMI (P < 0.001 and P = 0.046), respectively and vaccination (P = 0.002 and P = 0.01), respectively, with risk for malnutrition. There was no significant association between Diabetes (DM) and malnutrition risk, but elderly Cardiovascular Disease (CVD) were at malnutrition risk using the NRS- 2002 tool P = 0.003. Inversely, people infected six months or more before malnutrition assessment have a lower risk of malnutrition P = 0.05. CONCLUSIONS: Both tools were valuable and practical tools for screening elderly people with COVID-19 who are at nutritional risk and those in need of additional nutritional intervention. Further research needed to be applied in the relationship between nutritional status during and post-infectious disease for elderly people using cross-sectional and intervention studies in order to prevent malnutrition complications in Saudi Arabia.


Assuntos
COVID-19 , Desnutrição , Humanos , Idoso , Estado Nutricional , Avaliação Nutricional , Síndrome de COVID-19 Pós-Aguda , Estudos Transversais , COVID-19/epidemiologia , Medição de Risco , Desnutrição/complicações , Desnutrição/epidemiologia , Desnutrição/diagnóstico
3.
Saudi Pharm J ; 32(2): 101932, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38261946

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant concern in both healthcare and community settings, as it causes numerous infections worldwide with high morbidity and mortality rates. One promising strategy is to target the quorum sensing (QS) system of MRSA using a dendrimer loaded with kinase inhibitor peptide. The present investigation has formulated a poly-amidoamine dendrimer (PAMAM) G5 dendrimer that is loaded with Quorum Quencher (QQ) peptide, which functions as a histidine kinase inhibitor. The particle average size of the formulated G5-QQ3 complex was determined to be 276 nm, and polydispersity index values of 0.33. The MIC50 for the formulated nanoparticles was 18 µM as demonstrated by a growth assay. Furthermore, the G5-QQ3 complex was able to inhibit the hemolysis activity of the MRSA with a concentration of 10 µM, and for Staphylococcus aureus was 3 µM. The G5-QQ3 complex possesses the ability to inhibit, penetrate, and eradicate biofilm in MRSA, Staphylococcus aureus, and different agr mutants with inhibition percentages ranging from 60 to 72%. Furthermore, live/dead viability assay confirmed the ability of the formulated nanoparticles to effectively kill all strains within the biofilm structure as evidenced by a confocal microscope, and the cytotoxicity of the G5-QQ3 complex was dose-dependent (p < 0.05). against RAW 264.7 cells. In general, the study confirmed that encapsulating QQ3 peptide within PAMAM G5 dendrimer results in a potent anti-virulence and anti-bacterial action and suggests a synergistic effect. The findings of this study have significant implications for the development of new treatments for MRSA infections, which are a major public health concern.

4.
Int J Nanomedicine ; 19: 609-631, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38264736

RESUMO

Introduction: The emergence of Neisseria gonorrhoeae-resistant strains represents one of the most urgent global threats. In this regard, C7-3 peptide is one of the anti-virulence therapies that has demonstrated promising anti-gonococcal activity. Accordingly, this research aimed to formulate C7-3 peptide and its derivatives in chitosan nanoparticles. Methods: The peptide loaded chitosan nanoparticles were prepared using ion gelation method, and their physicochemical characteristics were investigated. The anti-gonococcal and antibiofilm activity of prepared NPs was assessed, and their cytotoxicity in human ovarian cells was evaluated. Results: All prepared NPs were optimized for the smallest particle size of 136.9 to 168.3 nm. The EE% of C7-3, C7-3m1, and C7-3m2 CNPs reached 90.2, 92.5, and 91.8%, respectively. An in vitro release study demonstrated a continuous sustained-release pattern of C7-3 peptide from NPs. The SDS-PAGE assay confirmed the integrity of C7-3 peptide after the fabrication process. When comparing each peptide alone, the generated NPs demonstrated higher anti-gonococcal and anti-biofilm effectiveness against standard and resistant bacterial strains under anaerobic conditions. The cytotoxicity experiments revealed the cytocompatibility of NPs in HeLa cell lines. Given the advantages of enhanced anti-gonococcal activity of the C7-3 peptide and its derivatives when loaded with CNPs, as well as the antimicrobial properties of chitosan NPs, the reported NPs have great potential in the treatment of gonococcal infection.


Assuntos
Quitosana , Nanopartículas , Humanos , Neisseria gonorrhoeae , Células HeLa , Biofilmes
5.
Molecules ; 28(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37175381

RESUMO

Lung cancer is the main cause of cancer-related mortality globally. Erlotinib is a tyrosine kinase inhibitor, affecting both cancerous cell proliferation and survival. The emergence of oncological nanotechnology has provided a novel drug delivery system for erlotinib. The aims of this current investigation were to formulate two different polyamidoamine (PAMAM) dendrimer generations-generation 4 (G4) and generation 5 (G5) PAMAM dendrimer-to study the impact of two different PAMAM dendrimer formulations on entrapment by drug loading and encapsulation efficiency tests; to assess various characterizations, including particle size distribution, polydispersity index, and zeta potential; and to evaluate in vitro drug release along with assessing in situ human lung adenocarcinoma cell culture. The results showed that the average particle size of G4 and G5 nanocomposites were 200 nm and 224.8 nm, with polydispersity index values of 0.05 and 0.300, zeta potential values of 11.54 and 4.26 mV of G4 and G5 PAMAM dendrimer, respectively. Comparative in situ study showed that cationic G4 erlotinib-loaded dendrimer was more selective and had higher antiproliferation activity against A549 lung cells compared to neutral G5 erlotinib-loaded dendrimers and erlotinib alone. These conclusions highlight the potential effect of cationic G4 dendrimer as a targeting-sustained-release carrier for erlotinib.


Assuntos
Dendrímeros , Neoplasias Pulmonares , Humanos , Cloridrato de Erlotinib/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Pulmão
6.
Saudi Pharm J ; 31(4): 547-553, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37063445

RESUMO

Background: Ruboxistaurin (RBX) used to treat retinopathy in diabetic patients which caused by microvascular damage and leakage which contributes to visual loss. There are no published studies on the use of liquid chromatography-tandem mass spectrometry for development and validation of a simple, sensitive, and accurate method for measuring RBX in rat plasma. Method: Chromatographic separation of RBX was achieved using ultra-performance liquid chromatography. Multiple-reaction monitoring quantification used RBX [M + H] + ion at m/z 469.18 and daughter ions at m/z 84, 58.12, and 98.10. Atorvastatin was used as internal standard (IS), has a single daughter ion, and was identified using m/z 559.6 â†’ 249.9. Validation of the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for RBX in rat plasma for linearity (greater than0.997) was carried out at 25-1000 ng/mL. Results: In rat plasma, the accuracy was within 3.4%, and the intra- and inter-day precision was within 11.8%. Stability, recovery, and matrix effect were all within acceptable limits. The drug retention time (0.85 ± 0.03 min) was remarkably short. Conclusion: The method developed in the current study is suitable to quantify RBX in plasma or bulk doses.

7.
Saudi Pharm J ; 31(1): 170-179, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685302

RESUMO

Background: Multidrug-resistant (MDR) bacterial infections have become an emerging health concern around the world. Antibiotics resistance among S. pneumoniae strains increased recently contributing to increase in incidence of pneumococcal infection. This necessitates the discovery of novel antipnemococcal such as compound C3-005 which target the interaction between RNA polymerase and σ factors. Chitosan nanoparticles (CNPs) exhibited antibacterial activity including S. pneumonia. Therefore, the aims of the current investigation were to formulate CNPs loaded with C3-005 and characteristic their antimicrobial properties against S. pneumonia. Methods: The CNPs and C3-005 loaded CNPs were produced utilizing ionic gelation method, and their physicochemical characteristics including particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency (EE%), and in vitro release profile were studied. Both differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) were used for chemical characterization. The synthesized NPs' minimum inhibitory concentration (MIC) was determined using killing assay and broth dilution method, and their impact on bacteria induced hemolysis were also studied. Results: The NPs encapsulating C3-005 were successfully prepared with particle size of 343.5 nm ± 1.3, zeta potential of 29.8 ± 0.37, and PDI of 0.20 ± 0.03. 70 % of C3-005 were encapsulated in CNPs and sustained release pattern of C3-005 from CNPs was revealed by an in vitro release study. CNPs containing C3-005 exhibited higher antipnomcoccal activity with MIC50 of 30 µg/ml when compared with C3-005 and empty CNPs alone. The prepared C3-CNPs showed a reduction of bacterial hemolysis in a concentration-related (dependent) manner and was higher than C3-005 alone. Conclusions: The findings of this study showed the potential for using C3-005 loaded CNPs to treat pneumococcal infection.

8.
Int J Mol Sci ; 25(1)2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38203711

RESUMO

The genotoxicity of AuNPs has sparked a scientific debate, with one perspective attributing it to direct DNA damage and another to oxidative damage through reactive oxygen species (ROS) activation. This controversy poses challenges for the widespread use of AuNPs in biomedical applications. To address this debate, we employed four-dimensional atomic force microscopy (4DAFM) to examine the ability of AuNPs to damage DNA in vitro in the absence of ROS. To further examine whether the size and chemical coupling of these AuNPs are properties that control their toxicity, we exposed individual DNA molecules to three different types of AuNPs: small (average diameter = 10 nm), large (average diameter = 22 nm), and large conjugated (average diameter = 39 nm) AuNPs. We found that all types of AuNPs caused rapid (within minutes) and direct damage to the DNA molecules without the involvement of ROS. This research holds significant promise for advancing nanomedicines in diverse areas like viral therapy (including COVID-19), cancer treatment, and biosensor development for detecting DNA damage or mutations by resolving the ongoing debate regarding the genotoxicity mechanism. Moreover, it actively contributes to the continuous endeavors aimed at fully harnessing the capabilities of AuNPs across diverse biomedical fields, promising transformative healthcare solutions.


Assuntos
COVID-19 , Nanopartículas Metálicas , Humanos , Ouro , Espécies Reativas de Oxigênio , DNA
9.
Medicine (Baltimore) ; 101(48): e31949, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36482609

RESUMO

The coronavirus 2019 (COVID-19) pandemic has globally impacted all aspects of life since its emergence and spread. There is a strong biological assumption and progressing epidemiological data supporting the role of vitamin D (VD) in COVID-19 infection. This study aims to determine the knowledge about VD supplements to boost immunity against COVID-19 and if participation in specific behaviors has increased the consumption of VD supplements during social distance restriction in Saudi Arabia (SA) in May 2021. This cross-sectional study used a structured online questionnaire for 2369 SA people, including demographic characteristics and knowledge about VD supplements to boost immunity against COVID-19 showed that there was a significant association between sex and vitamin D deficiency (VDD) (P = .000), and having VDD was strongly associated with having another vitamin deficiency (P = .008). Additionally, there was a statistically significant difference between VDD and cardiovascular (P = .027) and respiratory diseases (P = .019). Almost half of the participants used VD supplements to reduce or heal their COVID-19 symptoms. The adverse association between having VDD and understanding of COVID-19 symptoms was statistically significant (P = .01). Ginger is commonly used as an alternative medicine for the treatment of VD. The administration of VD is now known to be of physiological significance for general health, and evidence suggesting the beneficial role of VD in the prevention and/or treatment of diseases, particularly infectious diseases, such as COVID-19, is increasing.


Assuntos
COVID-19 , Pandemias , Humanos , Vitamina D , Estudos Transversais , COVID-19/epidemiologia , Arábia Saudita/epidemiologia
10.
Antibiotics (Basel) ; 11(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36358133

RESUMO

This study aims to assess the prevalence and antibiotic-treatment patterns of respiratory tract infections (RTIs), prevalence and types of antibiotic-prescribing errors, and the cost of inappropriate antibiotic use among emergency department (ED) patients. A cross-sectional study was conducted at the ED in King Abdulaziz Medical City, Riyadh, Saudi Arabia. Patient characteristics (age, sex, weight, allergies, diagnostic tests (CX-Ray), cultures, microorganism types, and prescription characteristics) were studied. During the study, 3185 cases were diagnosed with RTIs: adults (>15 years) 55% and pediatrics (<15 years) 44%. The overall prevalence of RTIs was 21%, differentiated by upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) (URTI 13.4%; LRTI 8.4%), of total visits. Three main antibiotics (ATB) categories were prescribed in both age groups: penicillin (pediatrics 43%; adults 26%), cephalosporin (pediatrics 29%; adults 19%), and macrolide (pediatrics 26%; adults 38%). The prevalence of inappropriate ATB prescriptions was 53% (pediatrics 35%; adults 67%). Errors in ATB included selection (3.3%), dosage (22%), frequency (3%), and duration (32%). There is a compelling need to create antimicrobial stewardship (AMS) programs to improve antibiotic use due to the high number of prescriptions in the ED deemed as inappropriate. This will help to prevent unwanted consequences on the patients and the community associated with antibiotic use.

11.
Polymers (Basel) ; 14(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36080730

RESUMO

Pseudomonas aeruginosa contributes to many chronic infections and has been found to be resistant to multiple antibiotics. Pseudomonas use a quorum sensing system (QS) to control biofilm establishment and virulence factors, and, thus, quorum sensing inhibitors (QSIs), such as meta-bromo-thiolactone (mBTL), are promising anti-infective agents. Accordingly, this study intended to investigate the antibacterial and anti-virulence activity of mBTL-loaded calcium alginate nanoparticles (CANPs) against Pseudomonas aeruginosa and different QS mutants. The results show that the mBTL-CANPs had higher antibacterial activity, which was made evident by decreases in all tested strains except the ∆lasR/∆rhlR double mutant, with MIC50 (0.5 mg/mL) of mBTL-CANPs compared with free mBTL at MIC50 (˃1 mg/mL). The biofilm formation of P. aeruginosa and some QS-deficient mutants were reduced in response to 0.5-0.125 mg/mL of mBTL-encapsulating CANPs. The pyocyanin production of the tested strains except ∆lasA and ∆rhlR decreased when challenged with 0.5 mg/mL of mBTL-loaded NPs. The subsequent characterization of the cytotoxic effect of these NPs on human lung epithelial cells (A549) and cystic fibrosis fibroblast cells (LL 29) demonstrated that synthesized NPs were cytocompatible at MIC50 in both cell lines and markedly reduced the cytotoxic effect observed with mBTL alone on these cells. The resulting formulation reduced the P. aeruginosa strains' adhesion to A549 comparably with mBTL, suggesting their potential anti-adhesive effect. Given the virulence suppressing action, cytocompatibility, and enhanced anti-biofilm effect of mBTL-CANPs, and the advantage of alginate-based NPs as an antimicrobial delivery system these nanoparticles have great potential in the prophylaxis and treatment of infection caused by Pseudomonas aeruginosa.

12.
Pharmaceutics ; 14(7)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35890338

RESUMO

Ruboxistaurin (RBX) is an anti-vascular endothelial growth factor (anti-VEGF) agent that is used in the treatment of diabetic retinopathy and is mainly given intravitreally. To provide a safe and effective method for RBX administration, this study was designed to develop RBX nanoparticles using polyamidoamine (PAMAM) dendrimer generation 5 for the treatment of diabetic retinopathy. Drug loading efficiency, and in vitro release of proposed complexes of RBX: PAMAM dendrimers were determined and the complexation ratio that showed the highest possible loading efficiency was selected. The drug loading efficiency (%) of 1:1, 2.5:1, and 5:1 complexes was 89.2%, 96.4%, and 97.6%, respectively. Loading capacities of 1:1, 2.5:1, and 5:1 complexes were 1.6%, 4.0%, and 7.2% respectively. In comparison, the 5:1 complex showed the best results in the aforementioned measurements. The in vitro release studies showed that in 8 h, the RBX release from 1:1, 2.5:1, and 5:1 complexes was 37.5%, 35.9%, and 77.0%, respectively. In particular, 5:1 complex showed the highest drug release. In addition, particle size measurements showed that the diameter of empty PAMAM dendrimers was 214.9 ± 8.5 nm, whereas the diameters of loaded PAMAM dendrimers in 1:1, 2.5:1, 5:1 complexes were found to be 461.0 ± 6.4, 482.4 ± 12.5, and 420.0 ± 7.1 nm, respectively. Polydispersity index (PDI) showed that there were no significant changes in the PDI between the free and loaded PAMAM dendrimers. The zeta potential measurements showed that the free and loaded nanoparticles possessed neutral charges due to the presence of anionic and cationic terminal structures. Furthermore, the safety of this formulation was apparent on the viability of the MIO-M1 cell lines. This nanoformulation will improve the therapeutic outcomes of anti-VEGF therapy and the bioavailability of RBX to prevent vision loss in patients with diabetic retinopathy.

13.
Saudi Pharm J ; 30(7): 946-953, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35903530

RESUMO

Recently, the focus has been shifting toward Quorum sensing inhibitors which reduce Pseudomonas aeruginosa virulence factors, alleviating infections. In this work, me-ta-bromo-thiolactone (mBTL), a potent quorum and virulence inhibitor for the Pseudomonas aeruginosa strains, were formulated in calcium alginate nanoparticles (CANPs). Alginate is used as nutrients and as backbone virulence aspect for Pseudomonas and therefore was chosen. mBTL-loaded-CANPs were characterized for particle size, polydispersity index, zeta potential, morphology visualized by Transmission Electron Microscopy (TEM) and drug release profile. Chemical and physical analysis of formulated mBTL-loaded-CANPs were evaluated using Fourier transform infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC) and Physical stability of mBTL-loaded-CANPs assessed at various temperature 25 ± 1 °C, 4 ± 0.5 °C and -30° ± 1 °C over a period of 4 and 9 months. Synthesized CANPs showed nano-size particles ranging from 140 to 200 nm with spherical particles for plain CANPS and irregular shape for mBTL-loaded-CANPs with a sustainable release profile over 48hrs. FTIR showed stable structure of loaded-mBTL and DSC displayed no interaction between mBTL and polymer. State of released mBTL from CANPs kept at 25 °C, 4 °C and -30 °C over 4 and 9 months showed stable formula at room temperature which kept as a goal of nanoparticles storage. The findings of this study revealed successful preparation of mBTL-loaded-CANPs.

14.
IJID Reg ; 3: 268-274, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35720150

RESUMO

Objective: To evaluate the preparedness of Saudi healthcare facilities to handle the coronavirus disease 2019 (COVID-19) pandemic. Methods: Between April and June 2020, a cross-sectional study was conducted among Saudi hospitals using an online-administered English-language questionnaire by the Saudi Commission for Health Specialties. The questionnaire evaluates all aspects of risk management, infection control and preventative programmes that should be known and practised by all healthcare workers (HCWs). All HCWs in Saudi hospitals designated to accept patients with COVID-19 were involved in the study. Results: In total, 161 HCWs responded to the survey. General understanding of hospital risk management plans and infection prevention measures was found to be outstanding (80.4%), with no differences in responses by gender, education or occupation. Some differences in responses were found by age group and years of working experience. Most responses were from hospitals located in the Central Province (72.7%) and governmental hospitals (88%), and most provided family services (68%). Furthermore, the results showed that medical professionals received adequate training, which is recognized as the baseline for effective risk management and infection control and prevention procedures, policies and recommendations. Conclusions: Notwithstanding small differences between HCWs, this study found that all HCWs in Saudi hospitals had excellent knowledge of risk management plans and pandemic sub-plans of infection control and prevention policies, procedures and principles, which has aided the health authorities in Saudi Arabia in mitigating COVID-19 effectively.

15.
Artif Cells Nanomed Biotechnol ; 50(1): 198-207, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35762105

RESUMO

Recent evidence has implicated microRNA-219 (miR-219) in regulation of gene contributed in glioblastoma (GBM) pathogenesis. This study aimed to prepare miR-219 in chitosan (CS) nanoparticles (NPs), characterize and investigate their efficacy on human GBM cell line (U87 MG). NPs were prepared using ionic gelation method. The influence of process parameters on physicochemical characteristics of NPs was investigated. Apoptotic effect of miR-219 was examined on U87 MG cells. Formulated NPs showed particle size of 109 ± 2.18 nm, with poly dispersity index equal to 0.2 ± 0.05, and zeta potential of +20.5 ± 0.7 mV. Entrapment efficiency of miR-219 in loaded NP has reached 95%. The in vitro release study demonstrated sustained release pattern of miR-219 from CS-NPs. Gel retardation assay has confirmed the integrity of miR-219 after production process. The fabricated NPs reduced the survival of U87 MG cells to 78% after 24 h of post-transfection, and into 67.5% after 48 h. However, fibroblasts were not affected by the NPs, revealing their specificity for GBM cells. Given the tumour suppressing function of miR-219, and advantage of CS-NPs for gene delivery to the central nervous system, the presented NPs have a great potential for treatment of GBM.


Assuntos
Quitosana , Glioblastoma , MicroRNAs , Nanopartículas , Quitosana/química , Portadores de Fármacos/química , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Nanopartículas/química
16.
Molecules ; 27(10)2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35630561

RESUMO

Psoriatic arthritis is an autoimmune disease of the joints that can lead to persistent inflammation, irreversible joint damage and disability. The current treatments are of limited efficacy and inconvenient. Apremilast (APR) immediate release tablets Otezla® have 20-33% bioavailability compared to the APR absolute bioavailability of 73%. As a result, self-nanoemulsifying drug delivery systems (SNEDDS) of APR were formulated to enhance APR's solubility, dissolution, and oral bioavailability. The drug assay was carried out using a developed and validated HPLC method. Various thermodynamic tests were carried out on APR-SNEDDS. Stable SNEDDS were characterized then subjected to in vitro drug release studies via dialysis membrane. The optimum formulation was F9, which showed the maximum in vitro drug release (94.9%) over 24 h, and this was further investigated in in vivo studies. F9 was composed of 15% oil, 60% Smix, and 25% water and had the lowest droplet size (17.505 ± 0.247 nm), low PDI (0.147 ± 0.014), low ZP (-13.35 mV), highest %T (99.15 ± 0.131) and optimum increases in the relative bioavailability (703.66%) compared to APR suspension (100%) over 24 h. These findings showed that APR-SNEDDS is a possible alternative delivery system for APR. Further studies are warranted to evaluate the major factors that influence the encapsulation efficiency and stability of APR-containing SNEDDS.


Assuntos
Nanopartículas , Sistemas de Liberação de Medicamentos , Emulsões , Tamanho da Partícula , Diálise Renal , Talidomida/análogos & derivados
17.
Diabetes Metab Syndr Obes ; 15: 1527-1535, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600752

RESUMO

Background: The persistent coronavirus disease 2019 (COVID-19) outbreak has placed a significant burden on the scientific and medical professions. The study examined the association between body mass index (BMI), stratified by category, and severe form of COVID-19, and to explore the influence of demographic characteristics and other known risk factors. Methods: This was a retrospective analysis based on COVID-19 data from the Saudi Arabian Ministry of Health. Data were collected for all patients admitted to three main hospitals in Riyadh region between March 1st and July 30, 2020. The effects of BMI, demographic characteristics, clinical presentation, and comorbidities on infection severity were investigated. Results: A total of 950 patients were included in the study (70% male, 85% aged younger than 60 years old). A total of 55 (5.8%) patients were underweight, 263 (27.7%) were normal weight, 351 (37%) were overweight, 161 (17%) were obese class I, 76 (8%) were obese class II, and 44 (4.6%) were obese class III. Cough, fever, and shortness of breath were the most common symptoms among overweight patients. According to the findings of a bivariate logistic regression study, class III obesity was significantly associated with a more severe form of COVID-19 (odds ratio, 2.874; 95% confidence interval, 1.344-6.149). Conclusion: This study revealed that patients with a BMI ≥40 kg/m2 had a higher risk of severe COVID-19 than those with normal weight. This suggests that obesity is a risk factor for severe COVID-19 and influences disease presentation.

18.
Pharmaceutics ; 14(2)2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35213977

RESUMO

Choroidal neovascularization (CNV) is a major cause of visual impairment that results from excessive growth of blood vessels in the eye's choroid. The limited clinical efficacy of the current therapy for this condition requires the emergence of new treatment modalities such as microRNA (miRNAs). A recent study identified microRNA-539-5p (miR-539) as an angiogenic suppressor in a CNV animal model; however, its therapeutic delivery is limited. Therefore, this study aims to formulate miR-539 in targeted nanoparticles (NPs) prepared from polylactic-co-glycolic acid (PLGA). The NPs were decorated with internalizing arginylglycylaspartic (RGD) peptide (iRGD), which specifically targets the alpha-v-beta-3 (αvß3) integrin receptor that is overexpressed in blood vessels of ocular tissue in CNV patients. The 1H NMR spectra results revealed successful conjugation of iRGD peptide into PLGA NPs. The miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs were prepared and showed a particle size of 300 ± 3 and 306.40 ± 4 nm, respectively. A reduction in human retinal microvascular endothelial cell (HRMEC) viability was shown 48 and 72 h post transfection with miR-539 incorporated in PLGA NPs and iRGD-PLGA.NPs. iRGD-functionalized PLGA NPs caused further significant reduction in cell viability when compared with plain ones, revealing an enhancement in the NP uptake with iRGD-grafted NPs. The current study showed that miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs are promising approaches that reduced the viability of HRMECs, suggesting their therapeutic potential in the treatment of CNV.

19.
Nanomaterials (Basel) ; 12(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-35010119

RESUMO

Colorectal cancer (CRC) is a serious disease that affects millions of people throughout the world, despite considerable advances in therapy. The formation of colorectal adenomas and invasive adenocarcinomas is the consequence of a succession of genetic and epigenetic changes in the normal colonic epithelium. Genetic and epigenetic processes associated with the onset, development, and metastasis of sporadic CRC have been studied in depth, resulting in identifying biomarkers that might be used to predict behaviour and prognosis beyond staging and influence therapeutic options. A novel biomarker, or a group of biomarkers, must be discovered in order to build an accurate and clinically useful test that may be used as an alternative to conventional methods for the early detection of CRC and to identify prospective new therapeutic intervention targets. To minimise the mortality burden of colorectal cancer, new screening methods with higher accuracy and nano-based diagnostic precision are needed. Cytotoxic medication has negative side effects and is restricted by medication resistance. One of the most promising cancer treatment techniques is the use of nano-based carrier system as a medication delivery mechanism. To deliver cytotoxic medicines, targeted nanoparticles might take advantage of differently expressed molecules on the surface of cancer cells. The use of different compounds as ligands on the surface of nanoparticles to interact with cancer cells, enabling the efficient delivery of antitumor medicines. Formulations based on nanoparticles might aid in early cancer diagnosis and help to overcome the limitations of traditional treatments, including low water solubility, nonspecific biodistribution, and restricted bioavailability. This article addresses about the molecular pathogenesis of CRC and highlights about biomarkers. It also provides conceptual knowledge of nanotechnology-based diagnostic techniques and therapeutic approaches for malignant colorectal cancer.

20.
J Complement Integr Med ; 19(2): 383-388, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34022123

RESUMO

OBJECTIVES: This study aimed to describe the development and implementation of a separated pathway to check and treat patients with a suspected/confirmed coronavirus disease 2019 (COVID-19) in the emergency department (ED) at King Abdullah bin Abdulaziz University Hospital in Riyadh. METHODS: We conducted a retrospective, descriptive longitudinal study from March to July 2020 by analyzing data of all confirmed cases of COVID-19 among ED visitors and healthcare workers in King Abdullah bin Abdulaziz University Hospital. RESULTS: During the study period, a total of 1,182 swab samples were collected for testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 285 (24.1%) tested positive. Of the 285 cases of confirmed SARS-CoV-2 infection, 18 were healthcare workers and 267 were patients. As a result of using the respiratory pathway for COVID-19 patients, the hospital managed to limit transmission of SARS-CoV-2 not only between patients but also between patients and healthcare workers, while also containing the pandemic. There were no cases of nosocomial SARS-CoV-2 infection recorded among the patients who visited the ED or the flu clinic. All confirmed cases were community acquired and patients were cared for under constrained measures. CONCLUSIONS: Implementing infection control measures and restricting those with respiratory symptoms to the ED pathway prevented nosocomial spread of SARS-CoV-2 infection in the ED.


Assuntos
COVID-19 , Infecção Hospitalar , COVID-19/prevenção & controle , Infecção Hospitalar/prevenção & controle , Serviço Hospitalar de Emergência , Humanos , Estudos Longitudinais , Estudos Retrospectivos , SARS-CoV-2
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