Inpatient allergy delabeling of pediatric patients with low-risk penicillin allergy status through direct oral amoxicillin challenge.

Background: Less than 5% of children who report penicillin allergy have clinically pertinent type 1 immunoglobulin E mediated hypersensitivity reaction by using direct oral amoxicillin challenge. Several pathways have been developed to delabel penicillin allergy by using direct oral amoxicillin challenge, mostly in the outpatient settings, but there is relative scarcity on published outcomes of these pathways, especially in the inpatient pediatric settings. Objective: This study aimed to evaluate the performance of an institutionally derived inpatient penicillin allergy screening tool. Methods: Patients were stratified into three penicillin allergy risk categories by using an institutional screening questionnaire. Patients with a no-risk status were delabeled without challenge testing. Patients with low-risk status underwent direct graded oral amoxicillin challenge and delabeled based on their response. Patients with high-risk status were referred to allergy service. Results: Ninety-two patients were identified with penicillin allergy. Forty of the 92 patients (43%) were screened. Of the 40 patients screened, 6 (15%) were identified as no risk, 28 (70%) were identified as low risk, and 6 (15%) were identified as high risk. Twenty-four of the 28 patients at low risk (86%) were eligible for direct amoxicillin oral challenge. Seventeen of the 24 (71%) consented to oral challenge but only 12 (71%) underwent direct amoxicillin oral challenge. Eleven of the 12 who underwent oral challenge (92%) were successfully delabeled. Five of the six patients at no risk (83%) were successfully delabeled. Three of the six patients at high risk (50%) were referred for further allergy evaluation. Overall, 16 of the 40 patients screened (40%) were successfully delabeled. Conclusion: In this small pediatric inpatient study, our institutional risk stratification screening tool identified patients at low risk for penicillin allergy and direct graded oral amoxicillin challenge was safely administered to delabel penicillin allergy in these patients.Clinical trial NCT05020327, www.clinicaltrials.gov.

Integrating HIV Pre-Exposure Prophylaxis (PrEP) Education During Medical Residency: Training Outcomes and Suggestions for Learning Effectiveness.

Human immunodeficiency virus (HIV) infection is now preventable with pre-exposure prophylaxis (PrEP) drugs, however, barriers to PrEP implementation include primary-care physician (PCP) knowledge-gap and lack of comfort prescribing and managing PrEP. We hypothesized that integrating HIV-PrEP education during medical-residency would help address these problems and developed a 40-minute case-based lecture focused on the 2021 United States Preventative Services Taskforce (USPSTF) oral HIV-PrEP guidelines and integrated this into our residency's core curriculum. We analyzed data from physician-trainees who voluntarily completed a pre- and post-lecture survey measuring HIV-PrEP "knowledge" and "self-assessed readiness to independently initiate and manage PrEP." Independent group analysis was completed via the Mann-Whitney U and Pearson Chi-square 2-sided test with P-value <0.05 deemed significant. Of the total of 189 residents invited to the lecture, 130 (69%) completed the pre-survey while 107 (57%) completed the post-survey. Per knowledge-assessment: the median number of correctly answered questions rose from a pre-lecture baseline of 4/9 (44%) to 8/9 (89%) following the education intervention (P < .001). When asked about comfort initiating and managing HIV-PrEP on their own, 7/130 (5.4%) responded in agreement pre-lecture, but this rose to 55/107 (51.4%) post-lecture (P < .001). Our study revealed PrEP training during residency was effective per stated objectives and may be an important tool to increase PrEP delivery/uptake to achieve the target goals for the National HIV/AIDS Strategy.

Severe COVID-19 outcomes in pediatrics: An observational cohort analysis comparing Alpha, Delta, and Omicron variants.

Objective: COVID-19 can rarely lead to severe illness in pediatric patients. The aim of this study was to determine if severe outcomes in pediatric COVID-19 have changed over the course of the pandemic. Methods: This was a multicenter, observational cohort analysis from a large regional healthcare system in metro Detroit using electronic health record data to evaluate emergency visits, hospitalization, and severe COVID-19 disease in pediatric patients. Consecutive pediatric patients presenting to the emergency department with a primary diagnosis of COVID-19 were included. Outcomes data was gathered from three distinct time intervals that coincided with Alpha, Delta, and Omicron variant predominance (Time interval 1 (T1) 1/1/2021-6/30/2021: Alpha, T2 7/1/2021-12/31/2021: Delta, T3 1/1/2022-6/16/2022): Omicron. The primary outcome was severe disease inclusive of composite intensive care unit admission, mechanical ventilation, multisystem inflammatory syndrome in children (MIS-C), myocarditis, or death. Secondary outcomes included severe outcomes considering viral coinfection and vaccination status. Results: Between 1/1/2021 and 6/16/2022, there were 4517 emergency COVID-19 visits, of which 12.5% (566) of children were hospitalized. 24.4% (138), 31.6% (179), and 44.0% (249) of admissions occurred during T1, T2 and T3 respectively. Most patients were male (55.1%) and 59.9% identified as Caucasian. The median age was 5.0 (interquartile range 1.0, 13.0) with infants comprising 22.8% (129), toddlers 25.1% (142), children 23.0% (130), and teenagers 29.2% (165). Over the course of the pandemic, the proportion of infants in hospitalization increased from 16.7% in T1 to 19.6% in T2 to 28.5% in T3 (p < 0.01) while the proportion of teenagers in hospitalization decreased from 39.1% in T1 to 31.3% in T2 to 22.1% in T3 (p < 0.001). Oxygen therapy was required in a minority (29.9%) of cases with supplemental oxygen utilized the least in T3 (16.5%) and most in T2 (30.2%). Composite severe disease decreased throughout the pandemic occurring in 36.2% in T1, 27.4% in T2, and 18.9% in T3. A multivariable logistic regression analysis revealed the odds of composite severe disease was significantly lower in T3 compared to T1 (adjusted odds ratio [aOR] 0.35, 95% Confidence Interval 0.21-0.60, p < 0.001). Fully vaccinated or fully vaccinated and boosted admission rates remained low throughout all periods with 4.4% in T1, 4.5% in T2 and 8.4% in T3. Viral coinfection was most common during T2 (16.8%) followed by T3 (12.5%) and least common in T1 (5.1%) (p = 0.006). Coinfection occurred more commonly in younger children with a median age of 1.2 (0.0, 4.5) compared to those with mono-infection with a median age of 6 (1.0, 14.0) (p < 0.001). Severe outcomes occurred in 45.6% of coinfection cases compared to 22.1% without coinfection (p < 0.001). Conclusions: While Omicron cases had the highest admission frequency, severe illness was lower than Delta and Alpha variants. Coinfection with respiratory viruses increased the risk of severe outcomes and impacted infants more than older children. Funding: None.

Determining the Clinical Utility of 16S rRNA Sequencing in the Management of Culture-Negative Pediatric Infections.

The use of 16S rRNA sequencing in culture-negative infections has improved identification of bacterial pathogens in select scenarios, but its clinical impact requires further elucidation, especially in the pediatric population. This retrospective study aims to determine the clinical utility of 16S rRNA sequencing on the clinical management of pediatric culture-negative infections in our institution. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples (p < 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility (n = 9, 30%), followed equally by joint fluid (n = 6, 20%) and bone (n = 6, 20%), with no difference between fluid and fresh tissue specimens (p = 0.346). Although the difference was not statistically significant (p = 0.4111), the overall use of broad-spectrum coverage was decreased. The median number of antibiotics was decreased from two to one (p < 0.0001) based on 16S rRNA sequencing results. The results suggest that 16S rRNA sequencing has a significant impact on decreasing the number of antibiotics used in the treatment of pediatric culture-negative infections. 16S rRNA sequencing performed on pulmonary specimens has the highest likelihood of identifying a pathogen compared to other specimen types. Additional cost-benefit analysis needs to be completed to further determine clinical benefit.

Clinical Characteristics and Etiology of Community-acquired Pneumonia in US Children, 2015-2018.

BACKGROUND: Pneumonia has a major impact on childhood health and health care costs. This study was designed to obtain contemporary information on the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children from both inpatient and outpatient settings in the USA. METHODS: We conducted a prospective, multicenter, observational study of CAP among previously healthy children 2 months to 18 years of age in 6 children's hospitals in Ohio from 2015 to 2018. For pathogen detection, nasopharyngeal swabs were collected from all subjects. Blood and pleural fluid cultures were available per standard of care. RESULTS: We enrolled a convenience sample of 441 patients: 380 hospitalized and 61 outpatients. Tachypnea and radiologic findings of consolidation and pleural effusion were more frequent among inpatients than outpatients. A pathogen was detected in 64.6% of patients: viruses in 55.6%, atypical bacteria in 8.8% and pyogenic bacteria in 4.3%. Eighteen (4.1%) patients had both viruses and bacteria detected. Rhinovirus/enterovirus (RV; 18.6%) and respiratory syncytial virus (RSV; 16.8%) were the viruses most frequently detected, and Mycoplasma pneumoniae (8.2%) and Streptococcus pneumoniae (2.3%) were the most common bacteria. Except for S. pneumoniae, which was identified more frequently in inpatients, there were no significant differences between inpatients and outpatients in the proportions of children with specific pathogens detected. CONCLUSIONS: Rhinovirus/enterovirus and RSV among viruses and M. pneumoniae and S. pneumoniae among bacteria were the most common pathogens detected in children with CAP. Tachypnea and chest radiographs with consolidation and/or pleural effusion were associated with hospitalization.

In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses.

Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.

Vitamin K & D Deficiencies Are Independently Associated With COVID-19 Disease Severity.

BACKGROUND: We investigated the association of vitamin K and vitamin D with coronavirus disease 2019 (COVID-19) outcomes. METHODS: Levels of inactive vitamin K-dependent dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP; marker of vitamin K status) and 25-hydroxyvitamin D (25(OH)D; vitamin D status) were measured in plasma samples from participants with confirmed acute COVID-19 and were age- and sex-matched to healthy controls. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% CIs were computed using cumulative logistic regression. RESULTS: One hundred fifty subjects were included, 100 COVID-19+ and 50 controls. The median age (interquartile range) was 55 (48-63) years, and 50% were females. Thirty-four percent had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (ie, worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL; P < .0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL; P = .09). Participants who were vitamin D deficient (<20 ng/mL) had the worse vitamin K status (dp-ucMGP >780 ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every 1-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death (AOR, 1.84; 95% CI, 1.01-3.45), and every 1-unit decrease in the natural log 25(OH)D was associated with >3 times the likelihood of severe COVID-19 disease (AOR, 0.29; 95% CI, 0.11-0.67). CONCLUSIONS: Early in acute COVID-19, both vitamin K and vitamin D deficiency were independently associated with worse COVID-19 disease severity, suggesting a potential synergistic interplay between these 2 vitamins in COVID-19.

Controlled bimatoprost release from graphene oxide laden contact lenses: In vitro and in vivo studies.

Ocular drug delivery using contact lenses may be able to substitute for eye drop therapy. However, issues with hydrophobic drugs (like bimatoprost that is used to treat glaucoma) such as low drug uptake using a simple soaking method into preformed contact lenses and alteration in the swelling and transmittance of lenses restricts the application for drug delivery. This research uses graphene oxide (GO) to control the release of bimatoprost from contact lenses along with improvements in the drug uptake, and lens swelling and transmittance. GO was loaded into silicone hydrogel contact lenses by adding the GO at the same time as lenses were polymerized. These lenses were soaked in bimatoprost. Alternatively contact lenses, either with or without GO, were produced by adding bimatoprost during lens polymerization. GO improved contact lens swelling due to its water binding capacity and lens transmittance due to the molecular dispersion of bimatoprost on the surface of the GO which prevented the local precipitation of the drug. The bimatoprost uptake was not improved in the presence of GO. However, its in vitro release profile was improved. Adding bimatoprost and GO at the same time as lenses were polymerized (DL-GO-BMT) significantly decreased the loss of drug during extraction and sterilization in comparison to contact lenses (DL-BMT) without GO. As the amount of GO was increased, the DL-GO-BMT lenses showed a significant decrease in the burst and cumulative release of bimatoprost. Ocular irritation and histopathology reports demonstrated the safety of GO contact lens. The in vivo pharmacokinetic studies in the rabbit tear fluid showed significant improvement in mean residence time (MRT) and area under the curve (AUC) with DL-GO-0.2 µg-BMT-100 contact lens in comparison to eye drop solution. The study demonstrated that the addition of GO to contact lenses can control the release of bimatoprost as well as improved the lens swelling and transmittance. However, further optimization is needed to modulate the release of drug within the therapeutic level to manage glaucoma.

The emerging role of cannabidiol (CBD) products; a survey exploring the public's use and perceptions of CBD.

The market value of cannabidiol (CBD) is growing as people seek holistic ways of managing their health. The aim of this study was to explore the public's perceptions and use of CBD products, including where products were sourced, knowledge transfer and opinions on quality, safety and efficacy of CBD products. An online questionnaire was distributed via social and professional networks, in addition to face-to-face data collection days, which employed convenience and snowball sampling methods. A total of 597 participant responses were analysed, of which 10.9% (n = 65) claimed to use CBD products for a range of ailments, including anxiety and pain. CBD products were bought from healthcare stores, vape stores, pharmacies and online. Of those who did not personally use CBD (n = 532), 35% claimed they would like to try it. A positive attitude towards the safety and efficacy of CBD was attributed to CBD being a natural product. The study highlighted that the public continue to seek natural alternatives to supplement and maintain their health; hence, the popularity of CBD continues to rise. The lack of clinical evidence and regulation of CBD needs to be addressed to facilitate safe and effective use of CBD.

Pediatric Patients with SARS-CoV-2 Infection: Clinical Characteristics in the United States from a Large Global Health Research Network.

Background Few reports have been published on the clinical presentation of pediatric patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aim to shed more light on the clinical presentation of pediatric patients infected with coronavirus disease 2019 (COVID-19), and also potential risk factors for more severe clinical case presentation. Methods We used a large global health research network to gather clinical data extracted from the electronic medical records of pediatric patients aged < 18 years with confirmed SARS-CoV-2 from January 1, 2020 to May 7, 2020. Clinical symptoms at presentation, hospitalization status, associated co-morbidities, and treatments received were reviewed. Results A total of 627 patients with COVID-19 diagnosis (334 were outpatient, 293 were inpatient) were included from a total of 20 organizations across the United States. The mean age of patients was seven years, 48% were females. Inpatients were younger than outpatients (mean age of 5.6 years vs 8.2 years, p<0.001). Sixty-one percent of patients in the inpatient group were < 5 years of age vs. 44% in the outpatient group. Amongst 293 inpatients, 90% (n=265) were non-severe and 10% (n=28) were classified as severe. The percentage of patients <5 years was higher in severe inpatients vs. non-severe (71% vs 60%.) Significantly more patients with a severe illness vs. non-severe illness had a history of co-morbidity including non-congenital heart disease (50% vs 11%, p<0.001) and disease of the respiratory system (86% vs 53%, p< 0.001). Conclusion Clinicians should closely monitor young children with underlying conditions and COVID-19, as they may be more likely to be hospitalized and have a higher severity of the disease.

Novel Poly(vinylpyrrolidone)-Coated Silicone Contact Lenses to Improve Tear Volume During Lens Wear: In Vitro and In Vivo Studies.

Poly(vinylpyrrolidone) (PVP-K90) is widely used to manage dry eye syndrome (DES). The marketed eye drop solutions (high dose) need frequent instillation, affecting the routine lifestyle of patients. PVP-K90-laden contact lenses can be used to overcome the limitations of eye drop solutions (low bioavailability and frequent instillation). However, the conventional methods of PVP-K90 loading show poor loading capacity and short duration of effect. In the present study, we have developed PVP-K90-coated contact lenses via a short curing approach to increase the PVP-K90 loading capacity with a sustained release profile to manage dry eye syndrome. PVP-K90 was loaded by a soaking method (SM-PVP), direct loading (during fabrication, DL-PVP), a combination of soaking and direct loading (DL-SM-PVP), and a novel coating process (SM-PVP-C and DL-SM-PVP-C). The swelling studies suggested improvement in the water uptake (hydration) property of the contact lenses due to the presence of PVP-K90. The optical transparency was within an acceptable range. The in vitro release of PVP-K90 was in the following order: PVP-coated contact lens (168 h) > DL-SM-PVP (168 h) > DL-PVP (96 h) > SM-PVP (72-96 h). PVP-coated contact lenses showed a high burst effect (lubricating effect) and sustained release (3161-448 ng/h between 24 and 168 h) due to high PVP loading/coating in comparison to the uncoated respective contact lenses (964-113 ng/h between 24 and 96 h). In animal studies, the PVP-K90-coated contact lens showed higher tear volume in comparison to the respective uncoated contact lenses and an eye drop solution. This study demonstrates a novel approach of coating a high amount of PVP-K90 on contact lenses for sustained release to manage several ocular diseases like dry eye syndrome, conjunctivitis, and other ocular injuries.

Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release.

A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.

Tailored gatifloxacin Pluronic® F-68-loaded contact lens: Addressing the issue of transmittance and swelling.

Loading of gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and gatifloxacin loading capacity as well as sustained drug delivery. Optimization of gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and gatifloxacin loading capacity of 92.56 µg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo gatifloxacin release data for rabbit tear fluid showed sustained release with a high gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.

Lidocaine tripotassium phosphate complex laden microemulsion for prolonged local anaesthesia: In vitro and in vivo studies.

Lidocaine is widely used as a local anaesthetic in the clinical practice to manage pre- and post-operative pain, skin burns, etc. However, the short duration of action (< 2 h) of marketed dosage forms limit their ability to meet clinical needs. Herein, we prepared a lidocaine-tPP(tri potassium phosphate)-complex loaded microemulsion to achieve greater penetration, followed by destabilization of microemulsion in the skin layer to precipitate oil-complex to produce a depot effect in the skin for prolonging the effects of anaesthesia. The lidocaine-tPP-complex-microemulsion was compared with lidocaine base loaded microemulsion, marketed ointment USP and lidocaine HCl. The pseudo ternary phase diagrams at three Smix ratios (1:2, 1:3 and 1:4; Pluronic F127: PEG 400) were constructed using Capmul MCM C8 EP as oil phase. The Smix at 1:4 ratio showed large microemulsion area in comparison to 1:2 and 1:6 ratio. The lidocaine base (LD-1:4-ME10O45SM and LD-1:4-ME20O45SM) and lidocaine-tPP-complex (LDC-1:4-ME10O45SM and LDC-1:4-ME20O45SM) loaded microemulsion batches (1:4 ratio) were thermodynamically stable. The ex vivo diffusion study showed sustained release up to 12 h with microemulsion batches, in comparison to lidocaine HCl (4 h) and ointment base (7 h). The selected LDC-1:4-ME20O45SM batch was non-irritating on the rabbit skin. In drug retention studies, LD-1:4-ME20O45SM and LDC-1:4-ME20O45SM batches showed 2.68- and 3.93-fold greater lidocaine retention in comparison to ointment USP. The radiant heat tail-flick test showed prolong local anaesthesia using LDC-1:4-ME20O45SM in comparison to ointment USP. The findings suggest that lidocaine-tPP-complex loaded microemulsion could be a potential strategy for providing prolong local anaesthesia.

Plackett-Burman design for screening of critical variables and their effects on the optical transparency and swelling of gatifloxacin-Pluronic-loaded contact lens.

The optical and swelling properties of gatifloxacin-loaded contact lens decrease owing to the precipitation of gatifloxacin (on hydration) in the matrix structure of the contact lens. This paper focuses on the use of Pluronic F68 both inside and outside (in the packaging solution) the contact lens to form micelles to dissolve the gatifloxacin precipitates and not limited to sustain the release of gatifloxacin. The aim of this study was to screen the critical variables affecting the optical and swelling properties of gatifloxacin-loaded contact lens. The independent variables investigated were the concentration of Pluronic F68 incorporated in the monomer solution to fabricate the lens (X1, %w/v), the concentration of Pluronic F68 in the packaging solution (X2, %w/v), the concentration of gatifloxacin incorporated in the monomer solution (X3, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during autoclave (X4, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during extraction (X5, %w/v), the time (stabilization time) after the addition of gatifloxacin and Pluronic F68 to the monomer solution before the fabrication of the lens (X6, h), the pH of the packaging solution (X7), the temperature of the extracted solution (X8, °C), and the curing time for fabricating the contact lens (X9, min). The gatifloxacin-loaded contact lenses were characterized for their optical transmittances after sterilization on day 1 (Y1, %), optical transmittances after 7 days of sterilization (Y2, %) and swelling percentages after 7 days of sterilization (Y3, %). The selected variables showed responses that were in the ranges 53.5% to 97.2%, 51.3% to 92.6%, and 50.3% to 83.7% for Y1, Y2, and Y3, respectively. The data suggest that the presence of Pluronic F68 inside the contact lens (X1) reduced the optical and swelling properties of the contact lens, whereas the presence of Pluronic F68 in the packaging solution (X2) improved them through micelle formation. The other variables (X3 to X9) did not exhibit significant effects on the swelling and transmittance. This study revealed the potential of Plackett-Burman design to screen the selected critical variables that affected the optical and swelling properties of gatifloxacin-loaded contact lens.

Effect of gold nanoparticles on timolol uptake and its release kinetics from contact lenses: In vitro and in vivo evaluation.

Contact lenses are ideally suited for extended drug delivery to the ocular tissues, but incorporation of any particulate system affects the critical properties of the contact lens. Timolol loading by the conventional soaking method does not significantly alter the critical properties of the contact lens. However, there are challenges of low drug loading and high burst release. This research work aimed to investigate the effect of gold nanoparticles (GNPs) on loading and its release kinetics from the contact lens using the soaking method. In one approach, GNPs were loaded into the timolol soaking solution (GNPs-SS), and in another approach, GNPs were incorporated into the contact lenses (GNPs-CL) during fabrication. The contact lenses were soaked at two different concentrations of timolol (i.e., 2 mg/ml and 4 mg/ml). Swelling and optical transmittance were not significantly affected by the presence of GNPs in the contact lenses. A significant uptake/loading of timolol using the GNPs in both the approaches was observed. The in vitro flux data showed no significant improvement in the release rate profiles of timolol when using both approaches. However, the in vivo study in the rabbit tear fluid showed high timolol concentration with the GNPs-laden contact lens at all timepoints in comparison to the soaked contact lenses without GNPs. The in vivo pharmacodynamic study in rabbits showed a 2 mmHg average fall in intraocular pressure (72 h) using the GNPs-laden contact lenses, while the soaked contact lenses without GNPs and eye drops solution (0.5 %w/v) showed 2 mmHg. The drug distribution study in the ocular tissue showed a significant improvement in the drug deposition with the GNPs-laden contact lenses in the ciliary muscle and conjunctiva. This study successfully demonstrated the potential of GNPs to enhance the uptake of drug from the drug soaking solution to treat glaucoma without compromising the critical properties of contact lens. STATEMENT OF SIGNIFICANCE: In this study, we have overcome the limitation of the conventional soaking method of low drug loading and high burst release from the contact lenses. We have investigated the effect of gold nanoparticles (GNPs) on the timolol loading and its release kinetics from the contact lenses. The study revealed the potential of GNPs to enhance the uptake of timolol from the timolol soaking solution to treat glaucoma without compromising the critical lens properties.

Contact lenses with dual drug delivery for the treatment of bacterial conjunctivitis.

Currently, bacterial conjunctivitis is treated by frequent administration of antibiotic eye drop solutions, which is tedious and patient noncompliant. Contact lenses could be ideal medical devices to sustain the release of ophthalmic drugs, but the incorporation of the latter can alter the optical and physical properties of the lenses. In addition, many contact lens users have reported the pink eye syndrome, making them unsuitable as ocular medical devices. In the present study, we have designed a novel type of lenses containing semi-circular rings loaded with moxifloxacin HCl (a broad spectrum antibiotic) and hyaluronic acid (a comfort agent), respectively, in order to treat bacterial conjunctivitis without altering the critical lens properties. The drug loaded rings were implanted separately within the periphery of the contact lenses using the modified cast moulding technology. The atomic force microscopy report showed an average roughness of 22.27 nm for the implant lens, which was significantly lower in comparison to the marketed Freshlook® (116.27 nm) contact lens. The major amount of moxifloxacin HCl was leached (68.16-74.55%) during the monomer extraction and wet sterilization (autoclave) steps; hence the lenses were terminally sterilized by radiation and packaged under dry condition (dehydrated). The in vitro release data showed release for moxifloxacin HCl and hyaluronic acid up to 96 h. The in vivo drug release studies showed significant improvement [>MIC for Staphylococcus aureus] in the drug residence time in comparison to the eye drop therapy. The in vivo efficacy study in the staphylococcus aureus induced conjunctivitis showed equivalent healing effect with the single implant contact lens in comparison to the frequent high dose eye drop therapy. The study demonstrated the successful application of the implantation technology to co-deliver moxifloxacin HCl and hyaluronic acid from the contact lenses for the extended period of time to treat conjunctivitis.