Alternative Routes Of Administration Research Articles

Investigating the benefits and harms of hypodermoclysis of patients in palliative care: A consecutive cohort study

Background: Palliative populations are at risk for dehydration which can cause discomfort, distress and cognitive symptoms. Subcutaneous hydration (‘hypodermoclysis’) has been used as an alternative administration route to the more invasive intravenous route, but research is lacking on its net clinical effects (harms and benefits) for palliative populations, particularly in real world settings. Aim: To quantify prospectively the net clinical effects of hypodermoclysis in palliative patients with advanced disease who required supplementary fluids. Design: Multisite, multinational consecutive cohort study. Setting/participants: Patients receiving hypodermoclysis in an inpatient palliative care setting. Results: Twenty sites contributed data for 99 patients, of which 88 had complete benefits and harms data. The most common primary target symptom for infusion was generalised weakness (18.2%), and the most common non-symptom indication was supplemental hydration (31.8%). Benefits were experienced in 33% of patients in their primary target symptom, and in any symptom in 56.8%. Harms were experienced in 38.7% of patients (42% at Grade 1). Benefits increased with higher performance status, while harms were more frequent in patients with lower performance status (Australia-modified Karnofsky performance status ⩽40). Patients in the terminal phase of their illness experienced the least benefit (15.4% in any indication only) and had more frequent harms (38%). Conclusions: Hypodermoclysis may improve certain symptoms in patients in palliative care but frequency of harms and benefits may differ at certain timepoints in the illness trajectory. Further research is needed to better delineate which patients will derive the most net clinical benefit from hypodermoclysis.

Preclinical Safety and Pharmacokinetics of Heat Stable Oxytocin in Sublingual Fast-Dissolving Tablet Formulation.

The work reported here focuses on an evaluation of a novel heat stable formulation of a uterotonic peptide drug oxytocin involving stability testing under elevated temperatures and toxicokinetic response generated by sublingual (SL) administration in rabbits. The formulation was thermotolerant, maintaining the potency of oxytocin in the form of a fast-dissolving tablet at the end of 2-year storage at 30 °C/65% relative humidity with less than 5% loss in oxytocin content based on analytical high performance liquid chromatography (HPLC). The toxicokinetic results in rabbits showed that the fast-dissolving tablet was safe without any reactogenicity or toxicity associated with SL administration or the excipients present in the formulation. The SL route elicited rapid absorption of oxytocin in plasma within 5 min of administration although lower than intramuscular (IM) administration. IM resulted in area under the curve (AUC) values approximately 5 times higher than SL oxytocin. However, due to the limitations encountered during SL administration in an anesthetized rabbit model, the relevance of heat stable oxytocin formulation that has the flexibility to be adapted in different formats may warrant a human clinical study to determine whether therapeutically relevant plasma levels for treating postpartum hemorrhage can be generated via alternate non-injectable routes of administration.

Esketamine inhaled as dry powder: Pharmacokinetic, pharmacodynamic and safety assessment in a preclinical study

Ketamine and its enantiomer esketamine have gained much attention in recent years as potent, fast-acting agents for the management of treatment-resistant depression. However, an alternative to oral ketamine administration is required to ensure adequate systemic exposure as the drug undergoes extensive first-pass metabolism. We propose dry powder inhalation as a new esketamine delivery route. Here, we examine the pharmacokinetics, pharmacodynamics, toxicology and safety of this novel esketamine administration method. Esketamine (10 mg/kg) and ketamine racemate (20 mg/kg) were administered to rats by dry powder inhalation, intravenous injection or intratracheal instillation and the pharmacokinetics of these treatments were compared. Analyte concentration of ketamine stereoisomers and their metabolites was assessed by LC-MS/MS method. Esketamine showed a clinically relevant pharmacokinetic profile, with high bioavailability (62%) and relatively low maximum concentration peaks. Esketamine exhibited high penetration of the blood-brain barrier, but pharmacodynamic examinations of brain homogenates showed no changes in selected protein phosphorylation or expression analyzed by the immunoblotting method. We conducted GLP-compliant 14-day and 28-day general toxicity studies in rats and dogs, respectively, subjected to dry esketamine powder inhalation. The maximum daily dosages were 46.5 mg/kg and 36.5 mg/kg, respectively. We also performed pharmacological safety studies. Esketamine inhaled as dry powder had an expected safety profile consistent with its known pharmacological action. None of its observed effects were considered toxicologically significant. The pharmacological safety studies confirmed that the observed effects were transient and that inhaled esketamine had a good safety profile. Hence, our preclinical studies demonstrated that dry powder inhalation is a highly efficacious and safe delivery route for esketamine and may be a viable alternative administration route meriting further clinical development.

Fabrication and Modelling of a Reservoir-Based Drug Delivery System for Customizable Release.

Localized therapy approaches have emerged as an alternative drug administration route to overcome the limitations of systemic therapies, such as the crossing of the blood–brain barrier in the case of brain tumor treatment. For this, implantable drug delivery systems (DDS) have been developed and extensively researched. However, to achieve an effective localized treatment, the release kinetics of DDS needs to be controlled in a defined manner, so that the concentration at the tumor site is within the therapeutic window. Thus, a DDS, with patient-specific release kinetics, is crucial for the improvement of therapy. Here, we present a computationally supported reservoir-based DDS (rDDS) development towards patient-specific release kinetics. The rDDS consists of a reservoir surrounded by a polydimethylsiloxane (PDMS) microchannel membrane. By tailoring the rDDS, in terms of membrane porosity, geometry, and drug concentration, the release profiles can be precisely adapted, with respect to the maximum concentration, release rate, and release time. The release is investigated using a model dye for varying parameters, leading to different distinct release profiles, with a maximum release of up to 60 days. Finally, a computational simulation, considering exemplary in vivo conditions (e.g., exchange of cerebrospinal fluid), is used to study the resulting drug release profiles, demonstrating the customizability of the system. The establishment of a computationally supported workflow, for development towards a patient-specific rDDS, in combination with the transfer to suitable drugs, could significantly improve the efficacy of localized therapy approaches.

Formulation and evaluation of different hydrogels loaded with Florite®-based etodolac adsorbate: In vitro and in vivo correlation

Owing to its poor solubility and oral bioavailability, etodolac (ETD), a selective COX-2 inhibitor, was formulated in high-dose oral tablets, which affect the gastrointestinal tract and cause a peptic ulcer and bleeding. Therefore, the topical administration of such a drug is an alternative route of administration. In the present work, we aimed to increase the solubility and enhance the dissolution rate of ETD through its adsorption on the surface of an inert adsorbent carrier, Flourite R (FR). Three ratios of ETD:FR were 1:1, 5:1, and 10:1, w/w. The ETD-FR adsorbates were characterized and evaluated, using different techniques such as X-ray and DSC. Three different gelling bases were used to construct the different hydrogel systems loaded with the medicated adsorbates. The hydrogel systems were subjected to different physicochemical characterizations, such as visual inspection, pH determination, and the studies of viscosity, spreadability, and extrudability. Moreover, the in vitro release and in vivo anti-inflammatory effects on rats were studied and correlated. The results revealed that the solubility of ETD adsorbates was significantly improved, with an excellent dissolution rate of 100% was achieved within 5 minutes compared to its original dissolution profile of 50% after 3 h. The data output of the DSC and X-ray indicated the conversion of ETD from the crystalline form into an amorphous one via the adsorption process had a major role in ETD improvement solubility. The hydrogels’ bases-incorporated ETD-adsorbates were significantly providing a remarkable improvement of its in vitro release rates compared to the plain ETD. The in vivo anti-inflammatory activities of constructed hydrogel systems were recorded at higher values compared with indomethacin capsules, with an extended duration of action (8 h). In conclusion, the obtained data confirmed that the modified hydrogel systems are promising vehicles for topical application of ETD in an effective and safe manner.

Managing Pain and Discomfort in Children with Cancer.

Approximately 15,600 children are diagnosed with cancer annually. Many of these children have cancer-related pain that improves with cancer treatment, but some develop intractable pain from cancer progression or sequelae from treatment modalities. The purpose of this paper is to provide a critical evaluation of the literature relevant to pain management in children with cancer. We intend to emphasize important and up-to-date findings in pharmacology, interventional pain management, and complementary and alternative medicine. Alternative medications and routes of administration, complementary and alternative medicine techniques, and interventional pain procedures offer possible routes for a multi-pronged pediatric cancer pain management plan, although high-level data is often lacking. To improve pediatric cancer pain management, a multifaceted approach embracing the biopsychosocial model of pain is recommended, incorporating evidence-based pharmacology, complementary and alternative medicine techniques, and if needed, interventional pain procedures.

Optimizing regional chemotherapy for epithelial ovarian cancer.

The response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the malignancy is not durable, and a majority of patients succumb to this disease process. It is possible that alternative types of chemotherapy and alternative routes of chemotherapy administration can improve the results of treatment and perhaps, reduce the morbidity and mortality that patients experience. Regional chemotherapy treatments previously presented in the ovarian cancer literature were reviewed and critically analyzed. New methods for chemotherapy delivery for both advanced primary and recurrent ovarian cancer were reviewed. This included hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) long-term. An important addition to perioperative chemotherapy delivery is the simultaneous use of heat with intraperitoneal drug delivery after a complete cytoreductive surgery. Drugs to be considered for HIPEC are cisplatin, gemcitabine, and melphalan. For EPIC, chemotherapy agents to consider include paclitaxel, pemetrexed, gemcitabine, and liposomal doxorubicin. For NIPEC, paclitaxel is the drug of choice usually combined with a systemic agent as bidirectional chemotherapy. Also, pemetrexed, gemcitabine, and liposomal doxorubicin are drugs to be considered for NIPEC in phase I/II trials. Innovative regimens of regional chemotherapy may improve the outcome of patients with advanced ovarian cancer. These chemotherapy treatments must be integrated with complete cytoreductive surgery and the availability of peritoneal access for repeated delivery of chemotherapy solutions.

Systemic immune response development in Albino rats after retrograde instillation of COVID-19 vaccine to submandibular salivary gland: An experimental study

ObjectiveThis study aimed to investigate whether using the submandibular gland duct (SMD) as an alternative mucosal route for vaccine administration induced anti-COVID-19 specific immunity. Material and methodsForty rats were randomized equally into four groups; Group I: Rats did not receive any intervention. Group II: Rats were subjected to intramuscular (IM) injection of COVID-19 vaccine. Group III: Rats were subjected to ductal cannulation by retrograde instillation of sterile saline into right SMD. Group IV: Rats in this group who had 0.5 ml of COVID-19 vaccine retrogradely injected into the right SMD. Subsequently, rats were examined for anti-COVID-19 specific antibodies (IgG). Also, light microscopic observation of glandular changes and immunohistochemical staining for CD20 was performed. ResultsThe obtained results demonstrated a significant increase in anti-COVID-19 IgG levels in all rats vaccinated via intraductal immunization (group IV) compared to group II. Histologically, ectopic follicles were found within the glandular lobules of the inoculated submandibular gland (SMG) in group IV. In addition, the nearby lymph node in group IV demonstrated reactive follicle characteristics in the form of activated secondary follicles with germinal centers (GCs). Immunohistochemically, CD20 was localized in group IV in GCs of the ectopic lymphoid tissue and the nearby lymph nodes while group I, group II, and III demonstrated negative immunoreactivity. ConclusionThe immune response demonstrated by intraductal SG immunization is generally more significant than that elicited by IM inoculation of the same vaccine.

Design and Development of Levodopa Loaded Polymeric Nanoparticles for Intranasal Delivery.

Intranasal delivery is an alternative administration route to deliver levodopa (L-Dopa) to the brain. This drug delivery route offers high drug permeability across the nasal epithelium and rapid absorption into the central nervous system (CNS) while bypassing first-pass metabolism. In this study, we developed a library of polymeric nanocarrier systems for L-Dopa utilising poly(lactic-co-glycolic acid) (PLGA) and chitosan. A total of three PLGA nanoparticles formulations (P1, P2 and P3) were prepared using a modified water-in-oil-in-water (W/O/W) solvent evaporation technique, while four formulations of chitosan nanoparticles (C1, C2, C3 and C4) were prepared by ionic gelation method with sodium tripolyphosphate (TPP) as a cross-linking agent. Upon characterising nanocarriers developed, it was discovered that C2 demonstrated the best results with regard to droplet size (553 ± 52 nm), polydispersity index (0.522), zeta potential (+46.2 ± 2.3 mV), and encapsulation efficiency (82.38% ± 1.63). Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) further corroborated the particle size analysis highlighting that C2 displayed uniform particle size with spherical morphology. Additionally, X-ray diffraction analysis (XRD) revealed that C2 was in an amorphous state while Fourier transform infrared (FTIR) analysis showed that there were no chemical interactions that might change the chemical structure of L-Dopa within the polymeric nanoparticle matrix. Lastly, an in-vivo intranasal study in male Wistar rats showed that the absorption of L-Dopa when formulated as chitosan nanoparticles was significantly enhanced (p < 0.05) by approximately two-fold compared to unmodified L-Dopa. Therefore, this work illustrates that formulating L-Dopa into chitosan nanoparticles for intranasal delivery is a potentially viable formulation strategy to improve the bioavailability of the drug for the treatment of Parkinson’s disease.

Development and optimization of Curcuma longa Linn. oleoresin non-aqueous gel for transdermal delivery

A long-term oral administration of NSAID and DMARD on rheumatoid arthritis (RA) treatment may cause gastritis, kidney, and cardiovascular disorder. One of the alternative therapies that have been investigated is by using herbal medicine such as Curcuma longa Linn. which contains curcumin and essential oils. Even though both compounds are quite effective in treating RA, poor aqueous solubility and low intestinal absorption limit their oral bioavailability. To overcome these drawbacks, transdermal delivery was chosen as an alternative route of administration. This study was aimed to formulate the Curcuma longa Linn. oleoresin into a transdermal non-aqueous gel system using Carbopol 934 and low substituted hydroxypropyl cellulose (4.25:0.75 %) as the gelling agent. In this study, multiple solvents (PEG 400, PG, glycerin, ethanol, and tween 20) were used in the system. The solvents were chosen based on their ability to dissolve the gelling agents. Optimization was done using a simplex lattice design based on the physical characteristics (viscosity, pH, spreadability, and adhesivity) of the prepared gel. The system with the optimum concentration of PEG 400 and PG was then observed for its stability and in vitro transport through snakeskin membrane using Franz diffusion cell with PBS pH 7.4 as acceptor medium. The optimal formula was comprised of 75% PEG and 25% PG which has a viscosity of 6.34 + 0.19 dPa.s, adhesivity of 6.05 + 0.11 seconds, pH of 5.16 + 0.09, spreadability of 6.94 + 0.06 cm, and quite stable after freeze-thaw cycling test, whilst around 26.85% curcumin was diffused through the membrane (flux = 0.084 mg.cm -2 ) after 2 hours. It can be concluded that the Curcuma longa Linn. oleoresin can be formulated into a non-aqueous gel system, which showed a fair gel physical characteristic with good stability and ability to permeate across the skin membrane, and is promising to be further developed as an alternative for RA treatment.

Apremilast in the Treatment of Plaque Psoriasis: Differential Use in Psoriasis.

Small molecule medications like apremilast are emerging as promising options for patients with psoriasis and other inflammatory conditions. Apremilast was approved by the Food and Drug Administration in 2014 for the management of both psoriasis and psoriatic arthritis. Apremilast inhibits phosphodiesterase-4, which increases the intracellular levels of cyclic AMP, thereby reducing inflammatory cytokine production. This review aims to discuss the published evidence and evaluate the differential use of apremilast in plaque psoriasis of the body and scalp, nail psoriasis, and palmoplantar psoriasis. In clinical trials, apremilast effectively reduced the severity of different dermatological manifestations of psoriasis and improved patients’ quality of life. It has an acceptable safety profile and is generally well-tolerated. Oral medications like apremilast offer an alternative route of administration which can be more convenient and appropriate for some patients. Additionally, pharmacoeconomic analyses of available anti-psoriatic systemic agents favor apremilast as a cost-effective therapeutic option.

Iontophoresis of Biological Macromolecular Drugs.

Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications.

Alternatives to Subcutaneous Immunotherapy for Allergic Rhinitis

Allergic rhinitis (AR) is an important public health issue worldwide due to its increasing prevalence and impact on quality of life, school performance, and work productivity. Subcutaneous immunotherapy (SCIT) is used to treat AR and involves repeated injections of allergen extracts. SCIT is used for cases of severe AR with symptoms that are not adequately controlled by medication, when the side effects of medication limit treatment options, or where the aim is to cure rather than symptomatically treat. Although SCIT is effective, it is not necessarily curative. Furthermore, there is also a low but present risk of systemic allergic reactions, with systemic side effects occurring in less than 0–1% of treated patients. Sublingual immunotherapy (SLIT) has emerged as an effective and safe alternative to SCIT. SCIT and SLIT are the only immunotherapies currently available for AR. In addition to sublingual administration as an alternative to SCIT, other routes of antigen administration have been attempted with the goal of increasing safety while maintaining efficacy. This review discusses the efficacies of SCIT and SLIT, their mechanisms, the utility of intralymphatic immunotherapy (ILIT) as an alternative route of antigen administration, and the potential for immunotherapy using other routes of antigen administration.

Alternative Routes of Administration of Clozapine.

Clozapine is the only antipsychotic with proven effectiveness in treatment-resistant schizophrenia. It is usually administered using commercially available oral tablets, but not all patients are willing or able to take medicines in this way. Orodispersible clozapine tablets are available from several manufacturers and may be useful where swallowing solid dosage forms is difficult, or as an aid to observe compliance. Liquid formulations of clozapine can be prepared extemporaneously or purchased commercially, but most preparations are suspensions (clozapine is poorly soluble) and patients may find them unpalatable. The administration of clozapine (suspension or crushed tablets) via enteral feeding tubes (predominantly nasogastric) has been reported both in medically unwell patients and in patients refusing clozapine. Enteral administration is likely to be superseded by intramuscular clozapine, which has recently been re-introduced and is being widely used in some countries. Successful use of this formulation in enforced treatment strategies has been described by several authors with good long-term outcomes when switched to oral treatment. Intramuscular clozapine has also been used in physically ill patients who are unable to take any form of enteral medication. Other methods of delivery (transdermal, nasal) are not yet commercially available, but offer promise of further treatment options for this group of seriously ill patients.

Opioids for Treatment of Pre-hospital Acute Pain: A Systematic Review.

IntroductionAcute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies.MethodsThe PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method.ResultsA total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine.ConclusionsAvailable evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00346-w.

Layer-by-Layer Assembly of Lipid Nanobubbles on Microneedles for Ultrasound-Assisted Transdermal Drug Delivery.

Microneedles as a typical device for transdermal drug delivery provide an alternative route for drug administration with minimal digestion by organs and better patient compliance. However, diffusion of passively released drug molecules within the skin tissue mainly depends on the interstitial fluid, which may be affected by different physiological conditions of individuals. Herein, we propose a nanobubble-modified microneedle patch for ultrasound-assisted drug delivery, which provides additional driving force for penetration and diffusion of the drug molecules. Layer-by-layer self-assembled drug-containing nanobubbles on the surfaces of microneedles trigger active drug release upon application of ultrasound. The concomitant microstreaming caused by cavitation effects facilitates the penetration and diffusion of drug molecules in the gelatin gel model and the ex vivo porcine skin model. The proposed drug delivery strategy holds great promise for rapid transdermal drug delivery with enhanced penetration and diffusion of the released drugs.

Formulacije bioloških lekova za alternativne puteve administracije - trenutni problemi i perspektive

Introduction: Biologics (biopharmaceuticals) present new promising therapies for many diseases such as cancers, chronical inflammatory diseases and today's biggest challenge - COVID-19. Research: Today, most biologics have been synthetized using modern methods of biotechnology, in particular DNA recombinant technology. Current pharmaceutical forms of protein/peptide biopharmaceuticals are intended for parenteral route of administration due to their instability and large size of molecules. In order to improve patient compliance, many companies are working on developing adequate forms of biopharmaceuticals for alternative, non-invasive routes of administration. The aim of this work is to review current aspirations and problems in formulation of biopharmaceuticals for alternative (non-parenteral) routes of administration and to review the attempts to overcome them. These alternative routes of administration could be promising in prevention and treatment of COVID-19, among other serious diseases. Conclusion: The emphasis is on stabilizing monoclonal antibodies into special formulations and delivery systems; their application should be safer, more comfortable and reliable. When it comes to hormones, vaccines and smaller peptides, some companies have already registered drugs intended for nasal and oral delivery.

Recent Progress in Self-Emulsifying Drug Delivery Systems: A Systematic Patent Review (2011-2020)

Self-emulsifying drug delivery systems (SEDDS) are lipid-based isotropic mixtures that enhance the bioavailability of poorly water-soluble drugs and reduce the possible side effects, offering a wide variety of treatments for several pathologies. The aim of this review is to discuss the state of the art of patents for this drug delivery system by studying recent patent applications (2011 to 2020). We performed a thorough screening using the European Patent Office's Espacenet database, from which 37 inventions were selected and fully studied. China had more patent applications, and the articles published about SEDDS exceeds both in number and technological advance the submitted inventions. Nevertheless, the patents presented herein are innovative to address known issues to traditional SEDDS, including storage and formulation stability, solid formulations, acute gastrointestinal toxicity from surfactants, and drug delivery through alternative routes of administration. This study also revealed that release behavior for SEDDS and associated pharmacokinetics were not completely disclosed by the inventors of the patents and that further studies are required.

Nanocarrier based drug delivery system – Future of Alzheimer disease

Alzheimer’s disease (AD) has risen to the top most cause of mortality in the world. Every twenty years, the illness rate doubles, affecting about one in every 10 households. AD is characterized by a gradual loss of neurons in the cerebral cortex, resulting in brain shrinkage. Senile neuritic plaques and neurofibrillary tangles become the disease’s primary characteristic. However, a continuous strategy is customized to cure AD effectively. However, as a result of difficulties in the medication delivery system induced by different barriers such as blood–brain barrier and cerebrospinal fluid has become the primary cause of therapeutic failure. Thus, to address these problems, nanotechnology is a potential technique for overcoming them. This study discusses the use of targeted delivery of medicament for the successful remedy and diagnosis of AD that utilizes nanocarriers as an alternative administration route, thus allowing the release of the drug into central nervous system.

Nasal vaccine as a booster shot: a viable solution to restrict pandemic?

The coronavirus disease 2019 (COVID-19) pandemic revolutionized the vaccine market and initiated the momentum for alternative routes of administration for vaccines. The intranasal route of immunization is one such possibility that appears to be the most promising since it has some significant advantages, particularly in the prevention of respiratory infection. To analyze and summarize the role of nasal vaccines over conventional vaccines during COVID-19 and the need for the nasal vaccine as a booster shot. In this narrative review, the required data was retrieved using keywords “COVID-19,” “Intranasal,” “Immunity,” “Nasal spray,” and “Mucosal” in databases including PubMed, Scopus, Embase, Science Direct, and Web of Sciences. The results of the study showed that the nasal vaccines were both effective and protective according to the current researches approaching during the COVID-19 period and the preclinical and clinical phase trials prove the intranasal vaccination elicits more robust and cross-protective immunity than conventional vaccines. In this narrative review article, mechanisms across the nasal mucosa will be briefly presented and the current status of nasal vaccines during the COVID-19 pandemic is summarized, and advantages over traditional vaccines are provided. Furthermore, after exploring the primary benefits and kinetics of nasal vaccine, the potential for consideration of nasal vaccine as a booster dose is also discussed.