Alternative Delivery Systems Research Articles

Blooming of insecticides from polyethylene mesh and film

Malaria remains a public health concern with vector control still the vital component of disease prevention, control, and elimination strategies. Recent years has seen a “stalling” in the progress made towards the reduction in the global malaria burden, highlighting the need to develop new, innovative, and safe alternative tools and delivery systems to achieve global malaria elimination. Interventions based on the use of indoor residual spraying (IRS) and long-life insecticidal bed nets (LLINs), i.e. insecticide-containing wall linings (IWLs), can contribute towards the reduction of malaria. Both LLINs and IWLs rely on the presence of insecticides on the fibre or filament surfaces. However, materials directly incorporating the insecticides into the polymer melt during extrusion, allows for effective killing of the mosquitoes when they come into contact with the surface of the material, only if there is insecticide present there. This means that the insecticide must migrate to the surface and precipitate there (bloom). Over time the internal concentration of insecticide will decay. This investigation was done using Fourier transform infrared spectroscopy (FTIR) in both the transmission and attenuated total reflection (ATR) modes to better understand the blooming of three World Health Organization-approved contact insecticides, i.e. alphacypermethrin, fipronil and chlorfenapyr, from mesh or film to better understand the likeliness of insecticides within the materials to migrate to the surface. Film-based samples were prepared in addition to wall lining mesh, because of their easier characterisation than the irregular shaped mesh filaments. FTIR, in ATR and in transmission modes, enabled the tracking of the migration of the three insecticides, over time to the surface of polyethylene mesh or film. This made it possible to estimate the apparent solubility of the insecticides in the polymer matrix. However, scanning electron microscopy (SEM) revealed that a portion of the insecticide is trapped, in a crystalline state, inside the polymer matrix. These results suggest the possibility of developing products-based insecticides for protection against infective mosquito bites in malaria-endemic regions.

Is the Covid-19 pandemic strong enough to change the online order delivery methods? Changes in the relationship between attitude and behavior towards order delivery by drone

Delivery of products in online orders by drones has begun to be tested by major retailers. How about consumers? Are they ready for this? Due to the emergence of Covid-19 and its easy transmission from person to person, considering the risks in the streets, a lot of people have started to place their orders online. However, the interaction between the courier and the consumer during the order delivery has become a problem over time. Reducing people's anxiousness in such pandemic situations brings uncertainty about the delivery of the orders. The object of the research is to create a drone delivery system, which is an alternative delivery system that will be solution to these problems and is also used in a limited way around the world. With this study, whose theoretical background is based on the diffusion of innovations theory, technology acceptance model and protection motivation theory, it is aimed to test the relationship between consumer's perceptions, attitudes and behavioral intentions towards drone delivery of online orders. In this research, questionnaire method has been used for data collection and measurement. Moreover, the Structural Equation Modeling approach has been used for data analysis and validation of models. According to the results of this study, significant relationships have been identified between the consumers' perception of benefit and risk, and attitudes and behavioral intentions towards drone delivery of online orders during pandemics.

Tumor-Derived Exosomes Enriched by miRNA-124 Promote Anti-tumor Immune Response in CT-26 Tumor-Bearing Mice.

Exosomes have been introduced as a new alternative delivery system for the transmission of small molecules. Tumor-derived exosomes (TEXs) not only contain tumor-associated antigens to stimulate antitumor immune responses but also act as natural carriers of microRNAs. The aim of the current study was to evaluate the efficacy of miR-124-3p-enriched TEX (TEXomiR) as cell-free vaccine in the induction of antitumor immune responses in a mouse model of colorectal cancer. Briefly, the exosomes were isolated from cultured CT-26 cell line, and modified calcium chloride method was used to deliver miR-124-3p mimic into the exosomes. We used a CT-26-induced BALB/c mouse model of colorectal cancer and analyzed the effect of TEXomiR on survival, tumor size, spleen and tumor-infiltrated lymphocytes, and splenocyte proliferation. Furthermore, intra-tumor regulatory T cells, cytotoxic activity of the splenocytes, and cytokine secretion was also evaluated to describe the anti-tumor immune response. When the tumor size reached 100 mm3, the mice were injected with TEXomiR, TEX, and/or phosphate-buffered saline (PBS) subcutaneously three times with 3-day interval, and then tumor size was monitored every 2 days. The in vitro results indicated that TEXs could efficiently deliver functional miR-124-3p mimic. The in vivo evaluation in tumor-bearing mice showed that treatment with TEXomiR can elicit a stronger anti-tumor immune response than unloaded TEX and PBS. Significant tumor growth inhibition and increased median survival time was achieved in tumor-bearing mice treated with TEXomiR. A significant decrease in CD4/CD8 and Treg/CD8 ratio in tumor tissue was demonstrated. Moreover, increased cytotoxicity and proliferation of splenocytes in the TEXomiR group compared to the TEX and PBS groups were identified. Taken together, our data demonstrated that tumor-derived exosomes efficiently deliver miR-124-3p mimic, and TEXomiR promotes anti-tumor immune responses.

Development of Apremilast Solid Dispersion Using TPGS and PVPVA with Enhanced Solubility and Bioavailability.

Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilast's low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its Cmax and AUClast were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.

Physiotherapists\u2019 perceptions of and willingness to use telerehabilitation in Kuwait during the COVID-19 pandemic

BackgroundTelerehabilitation has been considered a suitable alternative healthcare delivery system during the COVID-19 outbreak, and many studies have promoted its feasibility in delivering physical care to patients who live with pain and disability. Physiotherapists’ perceptions and willingness are two key factors that influence the provision of remote physiotherapy.AimTo investigate physiotherapists’ perceptions of and willingness to use telerehabilitation in Kuwait during the COVID-19 pandemic and to explore the barriers that may hinder the use of telerehabilitation in this sector.MethodsThe following methods were used: (1) a cross-sectional survey and (2) face-to-face semi-structured interviews. In the cross-sectional survey, an electronic questionnaire was sent to 747 physiotherapists who were working in the governmental health sector. The questionnaire included four sections: perceptions of telerehabilitation, comfort with technology, willingness to use telerehabilitation, and barriers to using telerehabilitation. Six interviews were conducted with physiotherapy managers to explore the barriers and facilitators of telerehabilitation practice.Data analysisIn this study, descriptive data analysis was conducted, and a cross-tabulation technique was used to find the associations between the variables, in which chi-square tests were used to identify the significance of the results, where p < 0.05. Thematic content analysis was used for the interviews.ResultsOnly 273 completed questionnaires were received, giving a response rate of 36.5%. Most of the respondents (237; 86.8%) considered telerehabilitation a viable option to deliver healthcare to patients during the COVID-19 pandemic. In spite of the lack of information and communication technology (ICT) (156; 57.1%), 89% (243) of the respondents were willing to integrate telerehabilitation into their conventional practice, as cultural and social norms were not against the use of telerehabilitation systems. The results indicate that the more the physiotherapists used the internet and email in their work and the more comfortable they were with technology, the more willing they were to use telerehabilitation systems (p = 0.01). The physiotherapy managers reported that patients’ privacy and the confidentiality of their data were considered barriers.ConclusionIn Kuwait, physiotherapists show overall positive perceptions towards and a willingness to use telerehabilitation to facilitate patients’ access to physiotherapy services. There are several barriers to employing telerehabilitation. Accordingly, recommendations are suggested.

Investigating the Drivers of Smoking Cessation: A Role of Alternative Nicotine Delivery Systems?

Since 2010, several nations with impressive histories of smoking cessation have witnessed the proliferation of Alternative Nicotine Delivery Systems (ANDS). Advocates suggest that ANDS offer an effective and safer substitute for combustible tobacco. Critics fear that ANDS could expose consumers to novel harms, discourage smoking cessation and may even renormalize tobacco use. Different nations have adopted radically different regulatory strategies ranging from outright bans to active encouragement of ANDS-led smoking cessation. Economic, social and political factors also influence rates of smoking and uptake of ANDS. An investigation into the national-specific context for smoking cessation; including the role of ANDS in reducing cigarette consumption, is likely of value to regulators around the world hoping to reduce smoking-related morbidity and mortality in their own communities. Five case studies were conducted to review the evidence from Australia, Canada, Japan, South Korea and the UK, drawing on an interdisciplinary framework for investigation combining sociological, ethnographic, policy analytic and econometric disciplinary approaches into a schema for studying the drivers of smoking cessation at the individual, micro, meso and macro levels. Data on smoking, and cessation from four decades was combined with more recent data on ANDS use, to investigate the relationship between tobacco control policies, ANDS use and smoking cessation, as well as other salient aspects of the national tobacco control landscape. Each case study developed specific recommendations for policy makers and the research agenda. This report summarizes the findings of those studies. Taxation and Stop Smoking Services (SSS) were among the most effective cessation drivers. Smoke-free laws were also found to be of value, though the evidence for their efficacy in reducing smoking prevalence is mixed. Other policies that sought to reduce the appeal or opportunity to smoke such as plain pack legislation and health warnings, etc. were less associated with short term reductions in smoking prevalence, though these may yet reduce national smoking rates by discouraging uptake among future generations. Tobacco use continues to be concentrated in socially and economically disadvantaged groups. Where regulations allowed, ANDS (e-cigarettes and heated tobacco in particular) were associated with smoking cessation. Moreover, instances of tobacco use declining even as e-cigarette use increased suggests that e-cigarettes do not necessarily re-normalize tobacco use as feared. The results demonstrate how policy decisions affect ANDS use and the latter’s value as a cessation mechanism. The authors recommend that regulators continue to increase tobacco taxes carefully and study how to integrate ANDS with well-funded SSS provision. Regulators should also seek policies that differentiate among nicotine products with respect to their harms profiles. Future cessation programs should target socially and economically disadvantaged groups where tobacco harms continue to be concentrated. This research highlights the need for high quality open-access data collection and analysis, especially regarding use of ANDS.

Formulation and Evaluation of Baclofen Polymeric Nanoparticles for Transdermal Delivery In-vitro and Ex-vivo Optimization

Objectives: Baclofen is a skeletal muscle relaxant with an anti-inflammatory effect. The current market products of baclofen are oral tablets and intrathecal injection which cause many undesirable systemic side effects. This study aimed to formulate topical formula of baclofen to decrease systemic side effects. Topical drug delivery systems formulated as nanoparticles (NPs) enhanced the low drug release and the low bioavailability of the traditional gels. This occurs by prolonging the contact time and increasing the permeability of the drug through the skin. Methods: In this study, formulae of the baclofen-loaded Eudragit® RL100 (ERL) NPs were prepared by nanoprecipitation method. Polyvinyl alcohol (PVA) was added as a stabilizer. The NPs were characterized by measuring their particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency percent (EE %) values. Their spherical morphology was confirmed using transmission electron microscopy (TEM). Viscosity was also measured. In vitro release and permeation studies were done to evaluate the release of the drug from the NPs gel and the permeability of the drug through the skin. The results were compared with formulated baclofen traditional gel. Results: ERL concentrationand organic phase ratio were the main factors affecting the NPs formulation. A decrease in the particle size was observed with an increase in ERL% while the smallest particle size was observed with formulae containing organic phase (acetone: methanol) in the ratio of 1: 3. The highest EE% was observed with the highest ERL concentration and the same organic phase ratio (acetone: methanol 1:3). Formulae B3, B6, B9 were selected for their most promising results. Their particle size was 187.4 ±2.81, 126.3 ±1.47, 120.0 ±1.06 nm and their EE% was 78.9 ±0.30, 83.3 ±0.26, and 86.6 ±1.12, respectively. The percentages of the drug released from the selected formulae as well as the percentage of the permeated drug were significantly higher than that of the baclofen traditional gel. Conclusion: ERL NPs were capable of releasing baclofen and improving its permeability through the skin so it may be considered as a suitable promising alternative drug delivery system.

Kidney-accumulating olmesartan-loaded nanomicelles ameliorate the organ damage in a murine model of Alport syndrome

ACE inhibitors or angiotensin II receptor blockers (ACEi/ARBs) have been a cornerstone of the management in kidney disease, but their use is often limited by undesired systemic effects, such as symptomatic hypotension. To minimize the extra-renal effects of ACEi/ARBs, we formulated hydrophobically modified glycol chitosan (HGC) nanomicelles releasing olmesartan (HGC-Olm) that specifically accumulated in the kidney, and investigated whether kidney-specific delivery of olmesartan by HGC nanomicelles could ameliorate organ damage in Col4a3−/− mouse, a murine model of progressive chronic kidney disease mimicking human Alport syndrome. Ex vivo tracing demonstrated that intravenously injected HGC-Olm nanomicelles were specifically delivered to the kidney, with sustained release of olmesartan for more than 48 h. Contrary to the conventional delivery of olmesartan via oral route, injection of HGC-Olm nanomicelles did not alter blood pressure in Col4a3−/− mice. Immunohistochemistry revealed that HGC nanomicelles were diffusely distributed from the cortex and glomeruli to the outer medulla, sparing the inner medulla. Phenotypic analysis showed that the attenuation of kidney fibrosis in the kidney of Col4a3−/− mice by HGC-Olm nanomicelles was comparable to that noted with conventionally delivered olmesartan. Therefore, our results suggest that HGC-Olm nanomicelles could be a safe and effective alternative drug delivery system for kidney diseases.

NANOPARTICLE INSULIN DRUG DELIVERY-APPLICATIONS AND NEW ASPECTS

Diabetes mellitus is a chronic metabolic disorder caused via the deficiency of pancreatic hormone insulin (Type1 diabetes mellitus) or due to the resistance of cells to insulin secreted by using the body (Type 2 diabetes mellitus). It is a rapidly growing serious situation that inspires a lot of global concern. Exogenous insulin administration is many times used therapy for Type 1 Diabetes Mellitus and gestational diabetes. The traditional subcutaneous insulin injections cause a lot of suffering to the affected person, exceptionally due to pain and secondarily due to dose sensitivity and in additional complications. Hence alternate delivery systems are an area of recreation for medical professionals and a convenient alternative system will be a boon to the patients. As an end result of the technological advances, various invasive and non-invasive delivery systems have been brought in the previous years. Nanotechnology, particle-mediated delivery, pulmonary delivery, buccal spray, etc. are the most current advances.

Carrier‐Based Systems as Strategies for Oral Delivery of Therapeutic Peptides and Proteins: A Mini‐Review

Peptides and proteins play an essential role in biological systems and the human body. Deficiency or dysfunction of peptides and proteins such as insulin can lead to various illnesses. The therapeutic use of peptides and proteins in some illnesses such as diabetes, cardiovascular disease, autoimmunity, and cancer, among others, is highly considered. Peptides and proteins have large molecular structures and are generally hydrophilic, and maintaining their spatial composition or tertiary configurations are necessary for their pharmacological activities. Maintaining the stability of the protein structure and composition is therefore very important and necessary to maintain functionality. There are different routes for peptides and proteins administration such as injection (subcutaneous, intravenous, and intramuscular), oral, nasal, pulmonary, rectal, and ocular routes. The oral administration route is better accepted by the patient due to safety and ease of use. However, oral administration often is unsuitable because of the physicochemical properties and macromolecular structure of proteins and the presence of gastrointestinal (GI) enzymes under an acidic environment within the stomach. Proteins and peptides undergo enzymatic degradation, tertiary structural alteration, and low absorption. This necessitates the need to use alternative oral drug delivery systems for peptides and proteins that maintain their overall structure and enhances their absorption and bioavailability. In this article, we review carrier-based oral drug delivery systems that were suitable for peptides and proteins.

FORMULATION AND EVALUATION OF TRANSDERMAL PATCH OF PLUMBAGIN FOR ANTI-FUNGAL ACTIVITIES

The objective of the current study is to improve the patient compliance and sustained drug release action by herbal medicine which can be achieved by developing alternative drug delivery system. The matrix type transdermal patches containing plumbagin were prepared by solvent evaporation method with different ratios of polymers (HPMC 50cps, PVP K29-32 and EUDRAGIT RS-100). In these matrix type transdermal patches, the PEG (Polyethylene glycol) was used as plasticizer and DMSO (Dimethyl sulfoxide) used as a penetration enhancer. The formulated patches were evaluated for physicochemical parameters like thickness, weight variation, % moisture content, % moisture uptake, % flatness, folding endurance and drug content. In vitro drug release studies were carried out by using the Franz diffusion cell. The cumulative % of drug released in 10 hours from the six batch formulations were 95.66%, 94.2%, 97.33%, 90.13%, 83.75% and 85.71%, respectively. On the basis of in-vitro drug release, formulation (HE-2) was found to be better than other formulation and these were selected for further evaluation such as anti-fungal activity and stability studies.

Intranasal drug delivery for treatment of Alzheimer's disease.

The Alzheimer's disease is a neurodegenerative condition with severe consequences interfering with patient quality of life. It is characterized as a progressive and irreversible brain disorder hampering memory and thinking, affecting the capacity to perform daily tasks leading to physical and cognitive incapacitation. The conventional treatment occurs by the oral route, but it presents relevant drawbacks such as low bioavailability, fast metabolism, limited brain exposure, and undesirable side effects. The intranasal route has been proposed as a promising alternative to deliver drugs and improve the Alzheimer's disease treatment. Still, there is not a clear alternative delivery system available in the market with advantageous bioavailability and safety. The aim of this review is to perform an overview on the strategies for drug intranasal delivery for Alzheimer's disease treatment. The advantages and disadvantages of this delivery route and the delivery systems developed so far are discussed. A special focus is given on the use of permeation enhancers, the types of intranasal drug delivery devices, as well as possible toxicity concerns.

Brain targeting of agomelatine egg lecithin based chitosan coated nanoemulsion

Intranasal drug delivery system has been proposed as an alternative delivery system to target agomelatine (AGO) to the brain and improving its bioavailability. Mucoadhesive egg lecithin nanoemulsions were optimized using D-optimal design and by investigating the effect of four independent variables: oil concentration (A), chitosan concentration (B), type of oil (C) and egg lecithin: oil (D). The responses of globule size, polydispersity index, zeta potential and drug content were evaluated. The optimized agomelatine mucoadhesive nanoemulsion (AGO MNE) with a desirability value of 0.856 was subjected to further investigations for mucoadhesion, in vitro diffusion, transmission electron microscopy and in vivo biodistribution. It showed significantly successful distribution to the brain, the optimized AGO MNE intranasal gave a brain targeting efficiency (BTE) of 278.71% indicating increased drug brain targeting by the nasal route compared with the intravenous route. Additionally, the optimized AGO MNE by intranasal had a direct transport percentage (DTP) of 64.109%, which indicates a significant contribution of the direct nose-to-brain pathway in the brain drug delivery. The study proposed egg lecithin mucoadhesive nanoemulsion as a successful and promising strategy to directly and efficiently deliver drug to the brain.

Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling.

Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At −20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.

Covid-19 shocks to education supply: how 200,000 U.S. households dealt with the sudden shift to distance learning.

Among the extraordinary shocks to household life caused by the Covid-19 pandemic was the sudden shift to distance learning in K-12 schools. Gone were Monday through Friday routines of school day, extracurricular activities, and evening homework; schools scrambled to launch alternative delivery systems, expecting parents to step in and spend significant amounts of time helping children continue to learn. This study examines the sudden shift to distance learning using data from U.S. Census Bureau’s Household Pulse Survey. Conducted weekly from April through July 2020, the survey tracked COVID-related shocks to employment, health, food and housing security, and education in the U.S. population. We use Pulse data on 200,000 households with K-12 children to examine how school systems shifted, how parents stepped up and spent time helping children learn, how parental time inputs varied with parent education, and how education changes intersected with other pandemic shocks, including job loss and food insecurity. We find that parents and children spent significantly more time in learning activities when their schools provided diversified educational inputs, especially live contact time with teachers; live contact hours also facilitated children learning on their own. Given the type of alternative schooling, less educated parents spent no less time helping children than better educated parents, although they faced significantly more problems with computer and internet access. Thus, parents generally tried to help children continue learning in the pandemic, albeit with potentially wide variation in the resources they could supply to mitigate the drop in learning.

Development and characterization of nano-emulsions and nano-emulgels for transdermal delivery of statins

ABSTRACT Background Oral administration of statins for the treatment of familial hypercholesterolemia results in poor therapeutic outcomes and patient compliance. An alternative administration route is proposed to circumvent the current limitations. This research is aimed at developing nano-emulsions and nano-emulgels as the ultimate potential delivery systems of statins for administration via the transdermal route. Methods Oil-in-water (o/w) nano-formulations (nano-emulsions and nano-emulgels) containing 2% (w/w) of the selected statin and 8% apricot kernel oil as oil phase were formulated. The nano-formulations were characterized using transmission electron microscopy (TEM), pH, viscosity, droplet size and zeta-potential. Results Nano-emulsions’ and nano-emulgels’ droplet size ranged between 114.23–169.83 nm and 149.83–267.53 nm, respectively. The addition of Carbopol® Ultrez 20 increased the nano-emulsions’ viscosity (3.59–8.38 cP) resulting in the formation of nano-emulgels (viscosity: 1911.00–46,090.00 cP). The entrapment efficiency (90.77–99.55%) confirmed the incorporation of the statins. Membrane release studies indicated that statins were released at higher flux values in nano-emulsions compared to their respective nano-emulgels. Ex vivo (skin diffusion) studies indicated higher median values in the nano-emulgels compared to their nano-emulsion counterparts. Conclusions The results indicate the benefits of nano-emulsions and nano-emulgels as potential alternative delivery systems for the transdermal delivery of statins.

Quantitative Analysis of Eugenol in Clove Extract and Nanoparticle Formulation by a Validated High-Performance Thin-layer Chromatographic Method

Eugenol (4-allyl-2-methoxyphenol) is the aromatic compound of the essential oil with the potential to modulate neuronal excitability. Nose to brain route of drug delivery via nanoparticle formulation has emerged as an alternative route drug delivery system for treatment of epilepsy. A selective and sensitive analytical method is required for evaluation of eugenol-based novel drug delivery systems. The objective of present study is to develop and validate a high-performance thin-layer chromatographic (HPTLC) method for the quantitative analysis of eugenol as bulk, in clove extract and in developed eugenol-loaded nanoparticle formulation. Chromatographic separation was achieved on silica gel pre-coated TLC aluminium plates 60F254, using methanol:distilled water (6:4, v/v) as the mobile phase. Quantitative analysis was carried out by densitometry at a wavelength of 280 nm. The method was validated as per ICH guidelines, to analyse eugenol in clove extract and to evaluate eugenol-loaded nanoparticles. Eugenol spots were observed at Rf value 0.58 ± 0.02. The detector response was linear (r = 0.9991) between 0.5 and 5.0 ng/spot. The intra- and inter-day precisions were 1.08–2.17 and 1.95-3.86 %, respectively. The limit of detection was 50 ng/spot and the limit of quantification was 150 ng/spot. The method proved to be simple, accurate, reproducible and rugged for eugenol. Evaluation of eugenol-loaded nanoparticle formulation demonstrated drug loading of 35.0%, encapsulation efficiency of 47.0% and sustained drug release following biphasic pattern. The present method is useful for the quantitative and qualitative analysis of eugenol and eugenol-loaded nanoparticle formulation. It provides significant advantages in terms of greater specificity and rapid analysis. © 2020 iGlobal Research and Publishing Foundation. All rights reserved.

Comment on: Safety and efficacy of a nepafenac punctal plug delivery system in controlling postoperative ocular pain and inflammation after cataract surgery

We have read the article by Donnenfeld et al. regarding nepafenac sustained-delivery punctal plugs with great interest.1 The authors present promising results and significant efficacy of the alternative drug delivery system, to be used after cataract surgery instead of topical treatment. Because the outcomes in contemporary cataract surgery partially depend on patient compliance, new therapeutic approaches, such as the one presented in this study, represent an appealing alternative. In the study, patients were randomized after cataract surgery to receive a nepafenac intracanalicular insert or a placebo. Other anti-inflammatory treatment was not permitted preoperatively, intraoperatively, or postoperatively, as stated by the authors. This part of the study design raises some concerns. Routine anti-inflammatory management after cataract surgery, including corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs), was not administered in the placebo arm; therefore, the patients in this group were exposed to a higher risk for adverse events.3 Such concerns were confirmed by the results of the study. More patients in the placebo group experienced pain at both day 3 (62% in the placebo group vs 31% in the treatment group) and day 7 (69% in the placebo group vs 33% in the treatment group), and worse visual acuity at day 7.1 The rescue medication protocol appears to provide a safety net for alarming levels of inflammation or pain. However, the same therapeutic hypothesis could be tested in a different research model. We believe that using a noninferiority study design could be beneficial. Since the 1990s, placebo-controlled trials have become ethically controversial if a standard treatment exists.2 A noninferiority trial aims to show that an experimental treatment is not worse than the accepted one.3 The new treatment might be safer, have better secondary endpoints, be easier to administer, or simply be less expensive. In ophthalmology, noninferiority trials are commonly applied for analyzing outcomes of age-related macular degeneration therapy and glaucoma treatment with prostaglandins. We believe that comparing the efficacy of the nepafenac insert with the accepted topical anti-inflammatory treatment is a good alternative in studies such as this one. Patients in the placebo group had worse outcomes, at least short term, and this could have been prevented with a noninferiority study design, while still offering the possibility of robust scientific scrutiny of the proposed treatment.

Growth Factor Therapy for Parkinson's Disease: Alternative Delivery Systems.

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

Nicotine in various delivery systems of it and its effect on the heart-rate variability

n this experimental study heart rate variability (HRV) using electrocardiography was studied in a small group of volunteers (10 people) who have never smoked (4), ex-smokers (4) and active smokers (2). Different nicotine delivery systems and smoking simulators, including regular, nicotine-free and electronic cigarettes, tobacco heating systems, chewing gums and a completely new product on the domestic market – nicotine packs of oral fixation (NPOF) were used. Supplemented with hormonal studies (stress hormones in saliva and catecholamines in the blood), HRV analysis showed relatively small changes in HRV with systemic use of packs with moderate nicotine content (up to 6 mg), which makes this type of product a leader in biological safety among the studied alternative delivery systems nicotine.