Route Of Drug Delivery Research Articles

Review Artikel: Metode Teknologi Dalam Sistem Penghantaran Obat Transdermal Sediaan Patch


 
 
 
 Transdermal is a route of drug administration through the skin, where many lipid layers are difficult to penetrate so that transdermal preparations are needed as a place for drug entry, for example creams and gels. The mechanism of drug delivery is through diffusion of the stratum corneum layer through lipid molecules, before releasing the drug in a controlled and constant manner followed by various other benefits and aims to increase the pharmacological effect in order to reach the maximum level. However, the permeability of the drug is not strong enough to pass through the stratum corneum. So we need a transdermal preparation that can work optimally and overcome the obstacles. This study aims to demonstrate the form, evaluation, formulation, and application of transdermal preparations in new drug delivery systems. Method used literature review of the 10 most journal articles and contains related information. Based on the research results, transdermal dosage forms differ depending on the level of concentration and each technological method needs adapted to the characteristics drug and the route of drug delivery given.
 
 
 

Polymers used in mouth dissolving film: A review

The oral route is one of the most important routes for local and systemic drug delivery, as it has a large surface, high permeability, and rich blood supply. Mouth dissolving films, are now becoming more popular than fast-dissolving tablets. The films are designed to disintegrate quickly when they come into touch with a surface that contains water, such the tongue. This allows the consumer to consume the product without the use of water. It can boost patient compliance and provide you a marketing advantage. The polymer used in mouth dissolving films is crucial to their quick dissolution and disintegration. The polymer must be non-toxic, non-irritating, flavorless, and simple to use. Natural and synthetic polymers are the two types of polymers that are employed. Natural polymers used in formulation of film include chitosan, gaur gum, xanthan gum, soy polysaccharide, gellan gum, locust bean gum, maltodextrin, and rosin. Hydroxypropyl cellulose, polyvinyl pyrrolidone, Hydroxypropyl Methylcellulose, Polyethylene Oxide, and Polyvinyl Alcohol are synthetic polymers that are frequently used to make films. The current overview gives a description of the numerous polymers that are utilized to make films that dissolve in the mouth.

Polymeric Biomaterials for Topical Drug Delivery in the Oral Cavity: Advances on Devices and Manufacturing Technologies.

There are several routes of drug administration, and each one has advantages and limitations. In the case of the topical application in the oral cavity, comprising the buccal, sublingual, palatal, and gingival regions, the advantage is that it is painless, non-invasive, allows easy application of the formulation, and it is capable of avoiding the need of drug swallowing by the patient, a matter of relevance for children and the elderly. Another advantage is the high permeability of the oral mucosa, which may deliver very high amounts of medication rapidly to the bloodstream without significant damage to the stomach. This route also allows the local treatment of lesions that affect the oral cavity, as an alternative to systemic approaches involving injection-based methods and oral medications that require drug swallowing. Thus, this drug delivery route has been arousing great interest in the pharmaceutical industry. This review aims to condense information on the types of biomaterials and polymers used for this functionality, as well as on production methods and market perspectives of this topical drug delivery route.

A Comprehensive Review: Transdermal Drug Delivery System: A Tool For Novel Drug Delivery System

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery and interest in life cycle management strategies among pharmaceutical companies. Transdermal drug delivery system was presented to overcome the difficulties of drug delivery especially oral route. Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of delivery system such as oral, topical, intravenous (i.v.), intramuscular (i.m.), etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin composition offers very effective barrier that allow only small molecule based drugs to penetrate the skin and pass through the barrier. Sildenafil citrate (SLD) is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor used for the oral treatment of erectile dysfunction and more recently, it has been used for the treatment of pulmonary arterial hypertension and the enhancement of uteroplacental perfusion in case of fetal growth retardation. The challenges facing the oral administration of the drug include poor bioavailability and short duration of action that requires frequent administration. The main objective of transdermal drug delivery system is to deliver drugs into systemic circulation through skin at predetermined rate with minimal inter and intrapatient variations. Keyword: Skin delivery, Transdermal drug delivery, Oral rout, Sildenafil citrate, Pulmonary arterial hypertension

Promising Role of Silk-Based Biomaterials for Ocular-Based Drug Delivery and Tissue Engineering.

Silk is a wonderful biopolymer that has a long history of medical applications. Surgical cords and medically authorised human analogues made of silk have a long history of use in management. We describe the use of silk in the treatment of eye diseases in this review by looking at the usage of silk fibroin for eye-related drug delivery applications and medication transfer to the eyes. During this ancient art endeavour, a reduced engineering project that employed silk as a platform for medicine delivery or a cell-filled matrix helped reignite interest. With considerable attention, this study explores the present usage of silk in ocular-based drug delivery. This paper also examines emerging developments with the use of silk as a biopolymer for the treatment of eye ailments. As treatment options for glaucoma, diabetic retinopathy, retinitis pigmentosa, and other retinal diseases and degenerations are developed, the trans-scleral route of drug delivery holds great promise for the selective, sustained-release delivery of these novel therapeutic compounds. We should expect a swarm of silk-inspired materials to enter clinical testing and use on the surface as the secrets of silk are unveiled. This article finishes with a discussion on potential silk power, which adds to better ideas and enhanced ocular medicine delivery.

Literature Review Article: Drug Delivery System Held in the Stomach (Gastroretentive)

Background: Medicine is a substance that through its chemical effects brings about changes in biological functions. The GRDDS delivery system is a sustained drug delivery system that can hold drugs back in the stomach for a longer time. The advantages of GRDDS include being able to increase bioavailability, increase the solubility of drugs that are poorly soluble in high pH, can control of therapeutic levels to reduce the occurrence of fluctuations, can extend the half-life so that the frequency of drug administration can be reduced.
 
 Objectives: This study aims to describe the types of GRDDS preparations. The variation is due to a combination of differences in mechanisms and technology.
 
 Method: The design in this study uses a systematic review of the review process that identifies, assesses, and interprets all findings on a research topic.
 
 Result: Floating systems can use expandable polymeric materials such as HPMC and chitosan. The floating mechanism begins with the contact of gastric juices with tablets which causes the polymer to hydrate to form a gel layer that can withstand CO2 gas formed due to the interaction of sodium bicarbonate with citric acid so that the tablets can expand and can float. The oral drug delivery route is the most preferred because it is easy to use. Absorption of oral drugs mostly occurs in the stomach and the intestines.
 
 Conclusion: Therefore, it is necessary to have a drug delivery system that can extend the contact time with the stomach, namely the Gastroretentive Drug Delivery System (GRDDS).

Safety and efficacy of a novel double-lumen tracheal tube in neonates with RDS: A prospective cohort study.

The purpose of this study was to assess the safety and efficacy of a new double-lumen tracheal tube for neonates, with a conventional tracheal tube as a control. Newborns with respiratory distress syndrome (RDS) requiring endotracheal intubation admitted to the tertiary neonatal intensive care unit (NICU) of Qujing Maternal and Child Healthcare Hospital in Yunnan Province between March 2021 and May 2022 were enrolled in this prospective cohort study. Outcome indicators related to effectiveness included mainly the number of intubations, duration of ventilation, duration of oxygenation, and length of stay; safety indicators included any clinical adverse effects during and after intubation. Appropriate stratified and subgroup analyses were performed according to the purpose of intubation, gestational age, and whether the drug was administered via endotracheal tube. A total of 101 neonates were included and divided into two groups based on the choice of tracheal tube: the conventional (n = 50) and new (n = 51) tracheal tube groups. There was no statistical difference between the two groups in terms of adverse effects during and after intubation (p > 0.05). In neonates who were mechanically ventilated without endotracheal surfactant therapy or newborns receiving InSurE technique followed by non-invasive ventilation, no significant differences were found between the two groups regarding any of the efficacy indicators (p > 0.05). However, for neonates on invasive mechanical ventilation, the new tracheal tube allowed for a significant reduction in the duration of mechanical ventilation (96.50[74.00, 144.00] vs. 121.00[96.00, 196.50] hours, p = 0.037) and total ventilation (205.71 ± 80.24 vs. 277.56 ± 117.84 h, p = 0.027), when used as a route for endotracheal drug delivery. Further analysis was performed according to gestational age for newborns requiring intratracheal surfactant administration during mechanical ventilation, and the data showed that for preterm infants, the new tracheal tube not only shortened the duration of mechanical ventilation (101.75 ± 39.72 vs. 155.50 ± 51.49 h, p = 0.026) and total ventilation (216.00 ± 81.60 vs. 351.50 ± 113.79 h, p = 0.010), but also demonstrated significant advantages in reducing the duration of oxygen therapy (9.75 ± 6.02 vs. 17.33 ± 8.43 days, p = 0.042); however, there was no statistical difference in efficacy outcomes between the two groups in full-term infants (p > 0.05). The efficacy and safety of this new tracheal tube are promising in neonates with RDS, especially those requiring surfactant administration via a tracheal tube during mechanical ventilation. Given the limitations of this study, however, the clinical feasibility of this catheter needs to be further confirmed in prospective randomized trials with larger sample sizes. http://www.chictr.org.cn/showproj.aspx?proj=122073.

Chitosan Aerogel Particles as Nasal Drug Delivery Systems.

The nasal drug delivery route has distinct advantages, such as high bioavailability, a rapid therapeutic effect, non-invasiveness, and ease of administration. This article presents the results of a study of the processes for obtaining chitosan aerogel particles that are promising as nasal or inhalation drug delivery systems. Obtaining chitosan aerogel particles includes the following steps: the preparation of a chitosan solution, gelation, solvent replacement, and supercritical drying. Particles of chitosan gels were obtained by spraying and homogenization. The produced chitosan aerogel particles had specific surface areas of up to 254 m2/g, pore volumes of up to 1.53 cm3/g, and porosities of up to 99%. The aerodynamic diameters of the obtained chitosan aerogel particles were calculated, the values of which ranged from 13 to 59 µm. According to the calculation results, a CS1 sample was used as a matrix for obtaining the pharmaceutical composition "chitosan aerogel-clomipramine". X-ray diffraction (XRD) analysis of the pharmaceutical composition determined the presence of clomipramine, predominantly in an amorphous form. Analysis of the high-performance liquid chromatography (HPLC) data showed that the mass loading of clomipramine was 35%. Experiments in vivo demonstrated the effectiveness of the pharmaceutical composition "chitosan aerogel-clomipramine" as carrier matrices for the targeted delivery of clomipramine by the "Nose-to-brain" mechanism of nasal administration. The maximum concentration of clomipramine in the frontal cortex and hippocampus was reached 30 min after administration.

Intrathecal pseudodelivery of Ab‐mAb alleviates pathology in an Alzheimer’s disease model

AbstractBackgroundIntrathecal pseudodelivery is a new route of drug delivery to the CNS based on an implantable device endowed with a smart system of nanoporous membranes. We have developed a miniaturized prototype of the device for rodents. Here we present preliminary results on the use of antiAbeta mAbs intrathecally pseudodelivered in the APP/PS1 mouse model of Alzheimer’s disease.Method28‐week‐old male mice, APP/PS1 and non‐transgenic were used. The device was implanted subcutaneously in the back of the mouse and connected to one of the lateral ventricles via a catheter, also subcutaneous. The reservoir of the devices was filled with artificial CSF (aCSF) or with a solution of anti‐amyloid beta (Ab) antibody (clone 6E10, Biolegend) in aLCR. The infusion period was three weeks, during which animal welfare aspects were assessed. After this time, the mice were sacrificed for histopathological evaluation. All procedures were performed in accordance with institutional guidelines approved by the Ethical Committee in Research of Universidad de Oviedo.Result Safety: The device was successfully implanted in a total of 18 mice. Three mice showed complications 3 days after surgery, including lethargy and significant weight loss. This could be due to the surgery itself or to the post‐operative medication. The rest of the mice recovered perfectly and returned to normal activity 4 days after surgery.Efficacy: Immunohistochemistry was performed to assess the size of Ab plaques, using a rabbit polyclonal anti‐Ab antibody (Invitrogen). The surface area occupied by the plaques in each of the APP/PS1 mice was determined. The results show a decrease in the area occupied by Ab‐positive plaques in the mice treated with the antibody. Although not statistically significant, there is a tendency for treated mice to have a smaller area occupied by plaques.ConclusionsOur results show that:• Intrathecal pseudodelivery of mAbs is a feasible route of drug delivery for neurodegenerative diseases.• Intrathecal pseudodelivery of Ab‐mAb alleviates pathology in an Alzheimer’s disease model.• Albeit preliminary efficacy and safety results are promising, further studies are needed.

Characterization of Eight Bacterial Biosensors for Microbial Diagnostic and Therapeutic Applications.

The engineering of microbial cells to produce and secrete therapeutics directly in the human body, known as advanced microbial therapeutics, is an exciting alternative to current drug delivery routes. These living therapeutics can be engineered to sense disease biomarkers and, in response, deliver a therapeutic activity. This strategy allows for precise and self-regulating delivery of a therapeutic that adapts to the disease state of the individual patient. Numerous sensing systems have been characterized for use in prokaryotes, but a very limited number of advanced microbial therapeutics have incorporated such sensors. We characterized eight different sensors that respond to physiologically relevant conditions and molecules found in the human body in the probiotic strain Escherichia coli Nissle 1917. The resulting sensors were characterized under aerobic and anaerobic conditions and were demonstrated to be functional under gut-like conditions using the nematode Caenorhabditis elegans as an in vivo model. We show for the first time how a biosensor is able to detect in vivo the bile acid-like molecule Δ4-dafachronic acid, a small molecule in C. elegans that regulates lifespan. Furthermore, we exemplify how bacterial sensors can be used to dynamically report on changes in the intestinal environment of C. elegans, by demonstrating the use of a biosensor able to detect changes in lactate concentrations in the gut lumen of individual C. elegans. The biosensors presented in this study allow for dynamic control of expression in vivo and represent a valuable tool in further developing advanced microbiome therapeutics.

Intranasal Administration of N-acetyl-L-cysteine Combined with Cell-Penetrating Peptide-Modified Polymer Nanomicelles as a Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis.

Intranasal administration is a promising route for direct drug delivery to the brain; its combination with nanocarriers enhances delivery. We have previously shown that intranasal administration combined with PEG-PCL-Tat (a nanocarrier) efficiently delivers drugs to the brain and exhibits excellent therapeutic efficacy against brain diseases. We aimed to clarify whether intranasal administration combined with PEG-PCL-Tat represents a useful drug delivery system (DDS) for amyotrophic lateral sclerosis (ALS) pharmacotherapy. We used N-acetyl-L-cysteine (NAC) as a model drug with low transferability to the spinal cord and determined the physicochemical properties of NAC/PEG-PCL-Tat. After intranasal administration of NAC/PEG-PCL-Tat, we measured the survival duration of superoxide dismutase-1 G93A mutant transgenic mice (G93A mice), widely used in ALS studies, and quantitatively analyzed the tissue distribution of NAC/PEG-PCL-Tat in ddY mice. The mean particle size and zeta potential of NAC/PEG-PCL-Tat were 294 nm and + 9.29 mV, respectively. Treatment with repeated intranasal administration of NAC/PEG-PCL-Tat considerably prolonged the median survival of G93A mice by 11.5 days compared with that of untreated G93A mice. Moreover, the highest distribution after a single administration of NAC/PEG-PCL-Tat was measured in the spinal cord. These results suggest that intranasal administration combined with PEG-PCL-Tat might represent a useful DDS for ALS therapeutics.

A Comprehensive Review on Targeted Drug Delivery System

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, and cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time.

A simple self-assembly nanomicelle based on brain tumor-targeting peptide-mediated siRNA delivery for glioma immunotherapy via intranasal administration

The blood-brain barrier (BBB) has a key role in preventing drugs from entering the brain. Non-invasive intranasal drug delivery routes that bypass the BBB are increasing in popularity because of their ability to shorten the journey and reduce the loss of genetic drugs such as siRNA in transit. However, the complex synthesis and quality control process of most nose-to-brain delivery carriers and the limited mass production are the main obstacles to their clinical application. Here, we constructed a siRNA delivery system with simple synthesis and quality control methods using cholesterol-modified T7 (T7-C), in which T7 can bind to the transferrin receptor (TfR) expressed on glioma cells to target gliomas. In our results, T7-C had dual functions as a glioma-targeting carrier and immune adjuvant. As a targeted delivery carrier, T7-C intranasally delivered siRNA into the mouse brain through the olfactory bulb pathway and was taken up by glioma cells by the caveolin- and transferrin-dependent pathway. As an immune adjuvant, T7-C could promote DC maturation and combined with slit2 siRNA could promote polarization of M2 subtype macrophages to M1 subtype macrophages and then increase the proportion of effector T cells to remodel the tumor environment. In conclusion, T7-C with glioma targeting as a delivery system of slit2 siRNA showed a good therapeutic effect in the treatment of glioma after intranasal administration and had potential application prospects. Statement of significanceIn contrast to the existing literature that uses complex materials to deliver drugs across the blood-brain barrier (BBB) in an invasive manner for glioma treatment, we developed a simple, self-assembling siRNA delivery system (T7-C) based on brain tumor-targeted T7 peptide to treat glioma by intranasal administration. T7-C/siRNA could reach the tumor site through the olfactory bulb route and adjust the “cold” tumor microenvironment to the “hot” tumor microenvironment and non-invasive intranasal delivery route could shorten the journey and reduce the loss of genetic drugs.Therefore, our design has good application prospects and is expected to serve as a general strategy for intranasal drug delivery in the treatment of brain tumors.

Research progress and innovation of drug delivery devices based on children's multidimensional demand for medication

Pediatric medication in China is characterized by a lack of child-specific drugs and insufficient types, specifications, dosage forms, and delivery devices. In recent years, new dosage forms with good compliance, such as inhalation preparation, rectal delivery system, and transdermal delivery system, have attracted more attention in pediatric medication. Because of the physiological characteristics of delicate viscera, difference in swallowing ability and psychological characteristics of fear of pain and aversion to bitter taste, it is particularly important to select suitable drug delivery route and drug delivery device according to children's physiological characteristics. With the help of the special drug delivery devices, traditional Chinese medicine and innovative Chinese medicine can be administered according to the expected design path, and drug delivery devices can ensure the accurate dose and improve the complia-nce to achieve the purpose of effective and safe drug delivery. It is also a way to realize the re-innovation of traditional Chinese medicine. The present study summarized the research progress in drug delivery devices for common drug delivery routes and new drug deli-very routes, put forward the innovative design idea of children's drug delivery devices according to the special needs of children, poin-ted out the compatibility of drug delivery devices and other problems in the current development, and prospected the application of intelligent information technology and additive manufacturing technology in drug delivery device innovation. This is expected to provide references for the development of innovative drugs and drug delivery devices suitable for children's multidimensional demand for medication.

A Review on Transdermal Patches

Since the start of life on the earth, humans have applied plenty of substances to their skin as cosmetics and therapeutic agents. However, it was the 20 th century once the skin became used as route for future drug delivery.Today about two third of drugs (available in market) are taken orally, but these aren’t as effective as required. To enhance upon the features the transdermal drug Delivery system was emerged. Amongst all techniques that transdermal drug delivery systems (TDDS), also referred to as “patches,” are dosage forms designed to deliver a therapeutically effective quantity of drug across a patient’s Skin. It give controlled continuous delivery of drugs via the skin to the systemic circulation. Advantage of transdermal drug delivery system are limitation of hepatic first pass metabolism, improvement of therapeutic potency and maintenance of steady plasma level of the drug. transdermal patch (Skin Patch) uses a special membrane to control the rate At which the liquid drug contained in the reservoir within the patch will pass through the skin and Into the bloodstream. Drugs administered through skin patches include scopolamine (for motion sickness), nicotine (for quitting smoking), estrogen (for menopause and to stop osteoporosis after menopause), nitroglycerin (for angina), and lidocaine to relieve the pain of shingles (herpes zoster).Transdermal patches were developed in the 1970s and the first was approved by the FDA in 1979 for the treatment of motion Sickness. IN 1981, patches for nitroglycerin were approved, and today there exist variety Of patches for drugs such as clonidine, fentanyl, Lidocaine, nicotine, nitroglycerin, estradiol, Oxybutinin, scopolamine, and testosterone. There are combination patches for Contraception, also as hormone replacement. Depending on the drug, the patches typically last from 1to7days. Non-medicated patch markets include Thermal and cold patches, nutrient patches ,skin care patches. Skin patch uses a special membrane to manage the rate at which the liquid drug contained in reservoir within patch will pass through the skin and into the bloodstream. Some drugs should be combined with substances, such as alcohol, that increase their ability to penetrate the skin so as to be used in skin patch. From last twenty years over thirty five transdermal products are approved generating sale of $3.2 billion in 2002,which is predicted to rise to $4.5 billion in 2008. TDDS are adhesive drug-containing devices of defined surface area that deliver predetermined quantity of drug to the surface of intact skin at a programmed rate to reach the systemic circulation. The greatest challenge for transdermal delivery is that only a limited number of medicine are able to administration by this route.Tansdermal route of administration is reflected as one of the potential route for The local and systemic delivery of drugs. Transdermal patches provides better therapeutic effect with minimum facet effects transdermal patches are designed to release the active ingredient at a zero order rate for a period of several hours to days following application to the skin.

Intraosseous administration into the skull: Potential blood-brain barrier bypassing route for brain drug delivery.

Progress in treating central nervous system (CNS) disorders is retarded owing to a limited understanding of brain disease pathology. Additionally, the blood-brain barrier (BBB) limits molecular entry into the brain. Many approaches for brain drug delivery to overcome the BBB, such as BBB permeability enhancement, transient BBB disruption, and direct surgical administration have been explored with limited success. Recent research has shown that direct vascular channels exist between the skull bone marrow and the meninges, allowing myeloid and lymphoid cells to migrate. We hypothesized that these direct channels may also allow brain drug delivery from the skull bone marrow to the brain. In this study, for the first time we propose intraosseous administration of drugs into the skull (intracalvariosseous [ICO]) as a novel approach for brain drug delivery via BBB bypassing routes. We tested the feasibility of the approach by applying nine representative compounds over thinned mouse skulls to simulate ICO and measuring the compound entry level in the brain compared to that after systemic administration. Surprisingly, we found that the skull is not completely impermeable to drug penetration into the brain and the tested compounds reached the brain tissue several tens-to-hundred times higher by ICO than systemic application. These findings suggest a role for the BBB bypassing route from skull to brain, apart from the systemic route, in the drug entry into the brain after ICO. This approach should be applicable to other CNS drugs and even BBB impermeable drugs. Overall ICO provides an innovative and advantageous pathway for effective treatment of brain diseases.

Thermoreversible Carbamazepine In Situ Gel for Intranasal Delivery: Development and In Vitro, Ex Vivo Evaluation.

Over the past decade, intranasal (IN) delivery has been gaining attention as an alternative approach to conventional drug delivery routes targeting the brain. Carbamazepine (CBZ) is available as an orally ingestible formulation. The present study aims to develop a thermoreversible in situ gelling system for delivering CBZ via IN route. A cold method of synthesis has been used to tailor and optimize the thermoreversible gel composition, using poloxamer 407 (P407) (15-20% w/v) and iota carrageenan (ɩ-Cg) (0.15-0.25% w/v). The developed in situ gel showed gelation temperatures (28-33°C), pH (4.5-6.5), rheological properties (pseudoplastic, shear thinning), and mucoadhesive strength (1755.78-2495.05 dyne/cm2). The in vitro release study has shown sustained release behavior (24h) for gel, containing significant retardation of CBZ release. The release kinetics fit to the Korsmeyer-Peppas model, suggesting the non-Fickian diffusion type controlled release behavior. Ex vivo permeation through goat nasal mucosa showed sustained release from the gel containing 18% P407 with the highest cumulative drug permeated (243.94µg/cm2) and a permeation flux of 10.16µg/cm2/h. After treatment with CBZ in situ gel, the barrier function of nasal mucosa remained unaffected. Permeation through goat nasal mucosa using in situ gel has demonstrated a harmless nasal delivery, which can provide a new dimension to deliver CBZ directly to the brain bypassing the blood-brain barrier.

Microneedle-mediated drug delivery for cutaneous diseases.

Microneedles have garnered significant interest as transdermal drug delivery route owing to the advantages of nonselective loading capacity, minimal invasiveness, simple operation, and good biocompatibility. A number of therapeutics can be loaded into microneedles, including hydrophilic and hydrophobic small molecular drugs, and macromolecular drugs (proteins, mRNA, peptides, vaccines) for treatment of miscellaneous diseases. Microneedles feature with special benefits for cutaneous diseases owing to the direct transdermal delivery of therapeutics to the skin. This review mainly introduces microneedles fabricated with different technologies and transdermal delivery of various therapeutics for cutaneous diseases, such as psoriasis, atopic dermatitis, skin and soft tissue infection, superficial tumors, axillary hyperhidrosis, and plantar warts.

Music improves the therapeutic effects of bevacizumab in rats with glioblastoma: Modulation of drug distribution to the brain.

BackgroundThe development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM via increasing BZM distribution to the brain along the cerebral vessels.MethodsThe experiments were performed on Wistar male rats (200–250 g, n=161) using transfected C6-TagRFP cell line and the loud rock music for OBBB. The OBBB was assessed by spectrofluorometric assay of Evans Blue (EB) extravasation and confocal imaging of fluorescent BZM (fBZM) delivery into the brain. Additionally, distribution of fBZM and Omniscan in the brain was studied using fluorescent and magnetic resonance imaging (MRI), respectively. To analyze the therapeutic effects of BZM on the GBM growth in rats without and with OBBB, the GBM volume (MRI scans), as well as immunohistochemistry assay of proliferation (Ki67 marker) and apoptosis (Bax marker) in the GBM cells were studied. The Mann–Whitney–Wilcoxon test was used for all analysis, the significance level was p < 0.05, n=7 in each group.ResultsOur finding clearly demonstrates that music-induced OBBB increases the delivery of EB into the brain tissues and the extravasation of BZM into the brain around the cerebral vessels of rats with GBM. Music significantly increases distribution of tracers (fBZM and Omniscan) in the rat brain through the pathways of brain drainage system (perivascular and lymphatic), which are an important route of drug delivery into the brain. The music-induced OBBB improves the suppressive effects of BZM on the GBM volume and the cellular mechanisms of tumor progression that was accompanied by higher survival among rats in the GBM+BZM+Music group vs. other groups.ConclusionWe hypothesized that music improves the therapeutic effects of BZM via OBBB in the normal cerebral vessels and lymphatic drainage of the brain tissues. This contributes better distribution of BZM in the brain fluids and among the normal cerebral vessels, which are used by GBM for invasion and co-opt existing vessels as a satellite tumor form. These results open the new perspectives for an improvement of therapeutic effects of BZM via the music-induced OBBB for BZM in the normal cerebral vessels, which are used by GBM for migration and progression.

Elucidating a Potential Mechanism of Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl) amino] Caprylate in Rats: Evidence of Lymphatic Absorption of Cyanocobalamin using the Mesenteric Lymph Duct Cannulated Rat

Oral administration is the most popular and convenient route for drug delivery, yet the success of oral drug delivery is dependent on the ADME properties of the drug. Among those ADME properties, permeability is considered one of the key attributes for successful oral drug absorption. Hence, the utilization of permeability enhancers to improve drug oral absorption is an important area of research in drug delivery. A multitude of data suggests that sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) is an effective permeability enhancer. Despite its success, the mechanism of how SNAC works to enhance the oral absorption of compounds is poorly understood. To better understand how SNAC worked, we investigated the hypothesis of SNAC promotes lymphatic absorption of target compounds. In this study, cyanocobalamin was used as the model compound and mesenteric lymph duct cannulated rats were used to investigate its absorption with or without SNAC. The present study demonstrated that SNAC enhanced the lymphatic absorption of cyanocobalamin when the two were co-dosed in rats. Furthermore, levels of SNAC in lymph fluid and the systemic circulation were higher when co-dosed with cyanocobalamin.