Development and In Vivo Evaluation of Sustained Release Microparticles Loaded with Levothyroxine for Hypothyroidism Treatment.

Hypothyroidism is a chronic condition combated by a daily oral supplementation of levothyroxine. In addition to the need for frequent dosing, oral administration may result in variable absorption of the drug leading to a failure in achieving normal thyroid function. Therefore, the development of a long-acting injectable system capable of delivering the drug is necessary. This work was aimed at developing sustained release microparticles loaded with levothyroxine. The microparticles were produced through the emulsification-solvent evaporation method using 2 grades of biocompatible and biodegradable polyesters: poly(ᴅ,ʟ-lactide-co-glycolide) (PLGA) and poly(ᴅ,ʟ-lactide) (PLA). Both polymers produced microparticles with very similar sizes (1.9 µm) and zeta potential values (around -22.0 mV). However, PLA microparticles had a significantly higher drug loading (6.1% vs. 4.4%, respectively) and encapsulation efficiency (36.8%, vs. 26.1%, respectively) when compared to PLGA counterparts. While both types of microparticles displayed a biphasic release pattern in vitro, a slower rate of release was observed with PLA microparticles. Moreover, a similar biphasic release pattern was found in vivo, with an initial phase of rapid release followed by a slower phase in the subsequent 10 days. These results indicate the possibility of developing levothyroxine loaded polyester microparticles as a potential long-acting thyroid hormone replacement therapy.

Nanocomposite orthopaedic bone cement combining long-acting dual antimicrobial drugs.

Antibiotic loaded bone cements are widely used in total joint replacement (TJR); despite many limitations such as a burst release which leads to antibiotic concentration below inhibitory levels and possibly contributing to the selection of antibiotic resistant strains. In order to address such limitations and to simultaneously address antibiotic resistance and short-term antimicrobial activity, we developed a nanocomposite bone cement capable of providing a controlled release of antimicrobial agents from bone cement to act as prophylaxis or treatment against prosthetic joint infections (PJIs). Gentamicin and chlorhexidine were loaded in combination on silica nanoparticles surface using layer-by-layer coating technique (LbL) combining hydrolysable and non-hydrolysable polymers. The drug release from the nanocomposite continued for >50 days at concentrations higher than the commercial formulation containing the same amount of antimicrobial drugs, where burst release for few days were observed. Moreover, the nanocomposite bone cement showed superior antimicrobial inhibition without adversely affecting the mechanical properties or the ability of osteoblasts to grow. In vivo experiments with an infected bone lesion model along with mass-spectrometric analysis also provided further evidence of efficacy and safety of the implanted nanocomposite material as well as its prolonged drug eluting profile. The developed nanocomposite bone cement has the potential to reduce PJIs and enable treatment of resistant established infections; moreover, the newly developed LbL based nano-delivery system may also have wider applications in reducing the threat posed by antimicrobial resistance.

Correlation of skin cancer and actinic keratosis-related knowledge and sun protection behaviors and sunscreen use among a sample of Jordanian population.

BACKGROUND: The incidence of skin cancer and actinic keratosis has increased worldwide. Measuring the public awareness, attitude, and knowledge about these diseases and the skin protection behaviors are highly important to undertake preventive measures. METHODS: To investigate skin cancer and actinic keratosis-related knowledge, sun protection behaviors, and sunscreen usage among Jordanians, a questionnaire was developed. The questionnaire was provided as a google form to individuals via social media and the data were analyzed using SPSS® 23. RESULTS: A total of 1277 individuals, aged 18-65 years filled the questionnaire. The median melanoma and actinic keratosis knowledge score were 7 (4-9) and 4 (0-9), respectively. The melanoma knowledge was higher among females, those with a medical background, a high level of education, and in the central region, whereas the AK knowledge was higher among those with a medical background. Overall, 75.9% of the participants used sunscreen at least often to prevent sunburn, uneven skin tone, or tanning, 72% were using sunscreen with an SPF of 30 at least. However, 45.3% and 49.2% of sunscreen users did not comply with application, and reapplication times, respectively. Moreover, 58.4% of participants applied less than the recommended amount of sunscreen. CONCLUSION: Our study revealed that public awareness of actinic keratosis is low among Jordanians. Although it was found that a high proportion of Jordanians use sunscreens there are deficits in sunscreen practice indicating an urgent need to design effective interventions to increase awareness of actinic keratosis and correct use of sunscreen via health campaigns or healthcare professions.

Ciprofloxacin-loaded dissolving polymeric microneedles as a potential therapeutic for the treatment of S. aureus skin infections.

Microneedles have been widely studied for many topical and transdermal therapeutics due to their ability to painlessly puncture the skin, thereby bypassing the stratum corneum, the main skin barrier. In this study, ciprofloxacin (CIP) was loaded into dissolving polymeric microneedles prepared by a two-layer centrifugation method as a potential treatment of skin infections such as cellulitis. The polymers used were polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Two formulations were investigated, namely CIP_MN1, composed of 10 mg ciprofloxacin incorporated into a polymer matrix of PVA and PVP with a weight ratio of (9:1), and CIP_MN2, composed of 10 mg ciprofloxacin incorporated into PVA polymer. CIP_MN1 and CIP_MN2 showed a mean microneedle height of 188 and 179 µm, respectively. Since Parafilm has been proven as a model to examine the perforation of microneedles in skin, it was used to evaluate the ability of microneedles to perforate the skin. CIP_MN1 showed almost complete perforation of Parafilm, 190 pores, compared to CIP_MN2 which created only 85 pores in Parafilm, and therefore CIP_MN1 was used for subsequent studies. Examining CIP_MN1 on agarose gel as an in vitro model of human skin showed that the formula was able to fully perforate the agarose gel. Moreover, this formula showed significantly greater antimicrobial activity (p < 0.0001) compared to a free gel of ciprofloxacin against Staphylococcus aureus in an agarose gel-based model. This was evidenced by a zone of inhibition of 29 mm for the microneedle formulation of ciprofloxacin (CIP_MN1) compared to 2 mm for the free gel of ciprofloxacin. Furthermore, the CIP_MN1 showed complete dissolution in human skin after 60 min from application. Finally, the skin deposition of CIP_MN1 was investigated in ex vivo excised human skin. CIP_MN1 showed significantly more deposition of ciprofloxacin in deeper skin layers compared to the free gel of ciprofloxacin, and the released ciprofloxacin from the microneedles tends to migrate to deeper layers with time. Collectively, these results suggest that CIP_MN1 can be a potential delivery system for the treatment of S. aureus skin infections.

Measuring a panic buying behavior: the role of awareness, demographic factors, development, and verification.

In this study, a new panic buying behavior (PBB) and awareness scales were established and verified during the Coronavirus Disease 2019 (COVID-19) pandemic. The PBB scales measured the relationship between people's awareness about COVID-19 and PBB. Moreover, this study investigated the potential association of some demographic factors with PBB. The online descriptive cross-sectional survey was collected from 429 Jordanians who were selected using the snowball sampling technique. The online survey started from April 1st to April 10th, 2020. Pearson correlation coefficient, one-way analysis of variance, independent sample t-test, and linear regression were used in this study. Findings indicated that both established scales were valid and reliable for achieving the required level of validity and reliability. In the current study, participants' awareness of COVID-19 was high; but, their PBB was low. Single and young individuals were positively associated with PBB. Awareness about COVID-19 and age were found to be the main predictors of PBB. This study concluded that the higher the awareness level about COVID-19, the lower PBB. High PBB may affect the world economy, highlighting the importance of COVID-19 awareness.

Workplace Violence among Healthcare Providers during the COVID-19 Health Emergency: A Cross-Sectional Study.

(1) Background: Workplace violence among healthcare providers (HCPs) is a tangible barrier to patient care. The purpose of this study was to gain insight into physicians' and nurses' perceptions of workplace violence and their perceptions of communication skills during the COVID-19 health emergency. We also sought to assess and compare the association between types of workplace violence, communication skills, and several sociodemographic factors of physicians and nurses including gender, marital status, site of work, age, and educational level during this era. (2) Methods: We performed a cross-sectional study of a selected hospital in Jordan using the Arabic version of the workplace violence and communication skills scales for September to November 2020. We included a total of 102 physicians and 190 nurses via a self-reported questionnaire. (3) Results: During the COVID-19 health emergency, physicians (48%) experienced workplace violence more than nurses (31.6%). More than two-thirds of the participants did not formally report any type of violence. Multinomial logistic regression analysis showed that marital status, gender, age, site of work, educational levels, and communication skills were associated with different types of violence among the two samples. (4) Conclusions: A high prevalence of workplace violence is noted among HCPs in Jordan compared with before the pandemic, which highlights the importance of promoting public awareness during crises.

Antimicrobial PMMA Bone Cement Containing Long Releasing Multi-Walled Carbon Nanotubes.

Prosthetic joint infections (PJIs) ensued from total joint replacement (TJR) pose a severe threat to patients that involve poor health outcomes, severe pain, death (in severe cases), and negative influence patients' quality of life. Antibiotic-loaded bone cement (ALBC) is frequently used for the prevention and treatment of PJI. This work aims to study gentamicin release from carbon nanotubes (CNTs) incorporated in polymethyl methacrylate (PMMA) bone cement to prolong release over several weeks to provide prophylaxis from PJIs after surgery. Different CNT concentrations were tested with the presence of gentamicin as a powder or preloaded onto carboxyl functionalized CNTs. The different types of bone cement were tested for drug release, mechanical properties, water uptake, antimicrobial properties, and cytocompatibility with human osteoblast cells (MTT, LDH, alizarin red, and morphology). Results showed prolonged release of gentamicin from CNT-loaded bone cements over several weeks compared to gentamicin-containing bone cement. Additionally, the presence of CNT enhanced the percentage of gentamicin released without adversely affecting the nanocomposite mechanical and antimicrobial properties needed for performance. Cytotoxicity testing showed non-inferior performance of the CNT-containing bone cement to the equivalent powder containing cement. Therefore, the developed nanocomposites may serve as a novel PMMA bone cement to prevent PJIs.

PMMA bone cement containing long releasing silica-based chlorhexidine nanocarriers.

Prosthetic joint infections (PJI) are still an extremely concerning eventuality after joint replacement surgery; growing antibiotic resistance is also limiting the prophylactic and treatment options. Chlorhexidine (a widely used topical non-antibiotic antimicrobial compound) coatings on silica nanoparticles capable of prolonged drug release have been successfully developed and characterised. Such nanocarriers were incorporated into commercial formulation PMMA bone cement (Cemex), without adversely affecting the mechanical performance. Moreover, the bone cement containing the developed nanocarriers showed superior antimicrobial activity against different bacterial species encountered in PJI, including clinical isolates already resistant to gentamicin. Cytocompatibility tests also showed non inferior performance of the bone cements containing chlorhexidine releasing silica nanocarriers to the equivalent commercial formulation.

Aqueous core microcapsules as potential long-acting release systems for hydrophilic drugs.

We have previously optimized the internal phase separation process to give rise to aqueous core microcapsules with polymeric shells composed of poly(lactide-co-glycolide) (PLGA) or poly(lactide) (PLA). In this study, the ability of these microcapsules to act as controlled release platforms of the model hydrophilic drug phenobarbital sodium was tested. Furthermore, the effect of the initial amounts of drug and water added to the system during microcapsule synthesis was investigated. Finally, the effect of varying polymer properties such as end functionalities, molecular weights, and lactide to glycolide ratios, on the characteristics of the produced microcapsules was studied. This was done by utilizing seven different grades of the polyester polymers. It was demonstrated that, within certain limits, drug loading is nearly proportional to the initial amounts of drug and water. Furthermore, drug encapsulation studies demonstrated that ester termination and increases in polymeric molecular weight result in lower drug loading and encapsulation efficiency. Moreover, drug release studies demonstrated that ester termination, increases in molecular weight, and increases in the lactide to glycolide ratio all result in slower drug release; this grants the ability to tailor the drug release duration from a few days to several weeks. In conclusion, such minor variations in polymer characteristics and formulation composition can result in dramatic changes in the properties of the produced microcapsules. These changes can be fine-tuned to obtain desirable long-acting microcapsules capable of encapsulating a variety of hydrophilic drugs which can be used in a wide range of applications.

Health-Related Quality of Life and Outcome after Total Knee Replacement: Results from a Cross-Sectional Survey in Jordan.

Total knee replacement (TKR) is a common procedure that is considered cost-effective with excellent long-term survivorship. This cross-sectional study, which includes 118 selected patients in Jordan from January 2020 to January 2021, aims to assess health-related quality of life (HQOL), functional status, and associated factors before and after 3 to 12 months of TKR. Furthermore, several demographical factors were included in this study to evaluate the potential association with the procedure's outcome. Western Ontario and McMaster Universities Osteoarthritis Index scale (WOMAC) and Short Form-36 (SF-36) scale were used in this study. It was found that the main change occurred 6-12 months after the procedure. Gender and age were found to be the primary predictor of quality of life among TKR patients. Patients before the TKR procedure experienced severe pain, joint stiffness, physical impairment, and psychological demand issues. After the TKR procedure, all symptoms were improved significantly. The TKR procedure can improve the quality of life for patients, which can be detected for several months after the procedure. Function and pain are the most critical indicators of improvement in quality of life. Assessing the quality of life is a key indicator for identifying patients without improvement, as well as improving the health care process and comparing other alternative interventions.

LbL-assembled gentamicin delivery system for PMMA bone cements to prolong antimicrobial activity.

INTRODUCTION: Antibiotic-loaded poly(methyl methacrylate) bone cements (ALBCs) are widely used in total joint replacement (TJR), for local delivery of antibiotics to provide prophylaxis against prosthetic joint infections (PJI). One of the shortcomings of the current generation of ALBCs is that the antibiotic release profile is characterized by a burst over the first few hours followed by a sharp decrease in rate for the following several days (often below minimum inhibitory concentration (MIC)), and, finally, exhaustion (after, typically, ~ 20 d). This profile means that the ALBCs provide only short-term antimicrobial action against bacterial strains involved PJI. RATIONALE: The purpose of the present study was to develop an improved antibiotic delivery system for an ALBC. This system involved using a layer-by-layer technique to load the antibiotic (gentamicin sulphate) (GEN) on silica nanoparticles, which are then blended with the powder of the cement. Then, the powder was mixed with the liquid of the cement (NP-GEN cement). For controls, two GEN-loaded brands were used (Cemex Genta and Palacos R+G). Gentamicin release and a host of other relevant properties were determined for all the cements studied. RESULTS: Compared to control cement specimens, improved GEN release, longer antimicrobial activity (against clinically-relevant bacterial strains), and comparable setting time, cytocompatibility, compressive strength (both prior to and after aging in PBS at 37 oC for 30 d), 4-point bend strength and modulus, fracture toughness, and PBS uptake. CONCLUSIONS: NP-GEN cement may have a role in preventing or treating PJI.

Role of poly-beta-amino-esters hydrolysis and electrostatic attraction in gentamicin release from layer-by-layer coatings.

Layer-by-layer (LbL) deposition is a versatile technique that has been employed in numerous industrial applications i.e. biomaterials, drug delivery and electronics to confer peculiar properties to the system. When LbL is employed for drug delivery, the active molecule is sandwiched between layers of polyelectrolytes and the release is controlled by the diffusion of the drug through the layers and the possible hydrolysis of the coating (delamination). Poly-beta-amino-esters (PBAEs) are a class of hydrolysable polyelectrolytes that have been widely used in DNA delivery and for LbL on medical devices. Their use allowed the controlled release of antibiotics and other bioactive compounds from the surface of medical devices without cytotoxic effects. The general accepted consensus is that drug released from LbL coating assembled using PBAEs is the results of the polymer hydrolysis; however, no attention has been paid to the role of the electrostatic attraction between PBAE and the other polyelectrolyte utilised in the LbL assembly. In this work, we prepared LbL coatings on the surface of silica nanoparticles entrapping gentamicin as model drug and demonstrated that the drug release from PBAEs containing LbL coatings is predominantly controlled by the electrostatic attraction between opposite charged electrolytes. The positive charge of PBAE decreased from pH = 5 to pH = 7.4 while alginate negative charges remained unchanged in this pH range while PBAE hydrolysis kinetics was faster, as determined with Gel Permeation Chromatography (GPC), in acidic conditions. When PBAE were employed in the LbL construct higher levels of drug were released at pH = 7.4 than at pH = 5; additionally, replacing PBAE with chitosan (the charge of chitosan is not influenced in this pH range) resulted in comparable gentamicin release kinetics at pH = 5.

Nano-carrier based drug delivery systems for sustained antimicrobial agent release from orthopaedic cementous material.

Total joint replacement (TJR), such as hip and knee replacement, is a popular procedure worldwide. Prosthetic joint infections (PJI) after this procedure have been widely reported, where treatment of such infections is complex with high cost and prolonged hospital stay. In cemented arthroplasties, the use of antibiotic loaded bone cement (ALBC) is a standard practice for the prophylaxis and treatment of PJI. Recently, the development of bacterial resistance by pathogenic microorganisms against most commonly used antibiotics increased the interest in alternative approaches for antimicrobial delivery systems such as nanotechnology. This review summarizes the efforts made to improve the antimicrobial properties of PMMA bone cements using nanotechnology based antibiotic and non-antibiotic delivery systems to overcome drawbacks of ALBC in the prophylaxis and treatment of PJIs after hip and knee replacement.