Topical Patch Research Articles

A Pivotal Study on the Safety and Effectiveness of a Targeted Alkali Thermolysis Patch for Treatment of Primary Axillary Hyperhidrosis or Excessive Axillary Sweating.

One-third of US adults are bothered by excessive sweating, approximately 5% are diagnosed with hyperhidrosis. A topical patch using targeted alkali thermolysis (TAT) was developed for treatment of this condition. This study was intended to assess the efficacy and safety of the TAT-Patch for axillary sweat reduction. A randomized, multicenter, double-blind, sham-controlled, pivotal trial enrolled 120 subjects to a bilateral axillary treatment with a TAT patch (63 subjects) or sham patch (57 subjects). The primary end point was achieved; 64% of TAT-treated versus 44% of sham-treated subjects (p = .0332) improved from Hyperhidrosis Disease Severity Scale (HDSS) 3/4 to HDDS 1/2 at 4 weeks. Targeted alkali thermolysis treatment also showed a statistically significant improvement over sham treatment for all secondary end points, including gravimetric sweat production and subject-reported quality-of-life (QoL) assessments. The duration of effect is approximately 3 months, determined by the time to return to baseline HDSS. Mild-to-moderate treatment-site adverse events (AEs) were reported in 22% of TAT patch subjects. No serious or severe AEs were reported. HDSS, GSP, and QoL findings confirm clinically meaningful sweat reduction and a significant improvement in quality of life following a single TAT patch treatment. This device has potential to offer a new, noninvasive treatment option that is well tolerated with minimal downtime.

Synthesis and Evaluation of Gelatin-Chitosan Biofilms Incorporating Zinc Oxide Nanoparticles and 5-Fluorouracil for Cancer Treatment.

In this study, a novel multifunctional biofilm was fabricated using a straightforward casting process. The biofilm comprised gelatin, chitosan, 5-fluorouracil (5-FU)-conjugated zinc oxide nanoparticles, and polyvinyl alcohol plasticized with glycerol. The 5-FU-conjugated nanoparticles were synthesized via a single-step co-precipitation process, offering a unique approach. Characterization confirmed successful drug conjugation, revealing bar-shaped nanoparticles with sizes ranging from 90 to 100 nm. Drug release kinetics followed the Korsmeyer-Peppas model, indicating controlled release behavior. Maximum swelling ratio studies of the gelatin-chitosan film showed pH-dependent characteristics, highlighting its versatility. Comprehensive analysis using SEM, FT-IR, Raman, and EDX spectra confirmed the presence of gelatin, chitosan, and 5-FU/ZnO nanoparticles within the biofilms. These biofilms exhibited non-cytotoxicity to human fibroblasts and significant anticancer activity against skin cancer cells, demonstrating their potential for biomedical applications. This versatility positions the 5-FU/ZnO-loaded sheets as promising candidates for localized topical patches in skin and oral cancer treatment, underscoring their practicality and adaptability for therapeutic applications.

Deferoxamine topical cream superior to patch in rescuing radiation-induced fibrosis of unwounded and wounded skin.

Topical patch delivery of deferoxamine (DFO) has been studied as a treatment for this fibrotic transformation in irradiated tissue. Efficacy of a novel cream formulation of DFO was studied as a RIF therapeutic in unwounded and excisionally wounded irradiated skin. C57BL/6J mice underwent 30 Gy of radiation to the dorsum followed by 4 weeks of recovery. In a first experiment, mice were separated into six conditions: DFO 50 mg cream (D50), DFO 100 mg cream (D100), soluble DFO injections (DI), DFO 1 mg patch (DP), control cream (Vehicle), and irradiated untreated skin (IR). In a second experiment, excisional wounds were created on the irradiated dorsum of mice and then divided into four treatment groups: DFO 100 mg Cream (W-D100), DFO 1 mg patch (W-DP), control cream (W-Vehicle), and irradiated untreated wounds (W-IR). Laser Doppler perfusion scans, biomechanical testing, and histological analysis were performed. In irradiated skin, D100 improved perfusion compared to D50 or DP. Both D100 and DP enhanced dermal characteristics, including thickness, collagen density and 8-isoprostane staining compared to untreated irradiated skin. D100 outperformed DP in CD31 staining, indicating higher vascular density. Extracellular matrix features of D100 and DP resembled normal skin more closely than DI or control. In radiated excisional wounds, D100 facilitated faster wound healing and increased perfusion compared to DP. The 100 mg DFO cream formulation rescued RIF of unwounded irradiated skin and improved excisional wound healing in murine skin relative to patch delivery of DFO.

Using Haptic Technology for Pain Reduction and Functional Improvement

Advancements to reduce pain severity and improve functionality are generally lacking. Chronic or recurrent pain is the most common reason patients consult primary care clinicians. Adverse events associated with existing pharmacological pain treatments have incentivized researchers to identify effective pain treatment strategies that have limited side effects, including non-invasive and non-pharmacologic options. Research has shown that a clearer understanding of the pain neuromatrix may assist in identifying alternative approaches and improving patient outcomes. A network consisting of neuronal pathways and circuits responding to sensory (nociceptive) stimulation makes up the neuromatrix of pain. Research provides strong support that these pathways and areas of the brain have elicited change in response to external stimuli. Advancements in the understanding of how external tactile stimuli, specifically “haptic vibrotactile trigger technology (VTT)” disrupts the neuromatrix of pain, has led to the development of technology that shows promise in targeting the nociceptive pathways. Through ongoing research, the technology has been incorporated into non-invasive, non-pharmacological topical patches and other routes of delivery to evaluate response as it relates to different health concerns and conditions. The purpose of this IRB-approved, minimal risk, randomized, and blinded study was to evaluate patients’ experiences and/or perceptions and patient response for those who received a haptic vibrotactile trigger technology (VTT) embedded non-pharmacologic, non-invasive, over-the-counter pain patch (FREEDOM Super Patch with VTT; Srysty Holding CO, Toronto, Canada) and those who received a placebo patch without the embedded technology. This final outcome data from the HARMONI Study adds to previously published interim data. Methods: Baseline, 7- and 14-day data were recorded in one hundred sixty-eight (168) adult subjects (107 females and 61 males) in a Treatment Group (n=148) or Control Group (n=20) with a mean age of 53 years who presented with mild, moderate and even severe musculoskeletal, arthritic and neurological pain. The study evaluated changes in overall severity and interference scores via a validated scale (Brief Pain Inventory (BPI)), changes in the use of prescription and OTC medications, patient satisfaction, and any side effects reported while using an active or placebo patch. Results: For the Treatment Group, results showed statistically significant decreases in mean BPI severity and interference scores after using the VTT embedded pain patch. After 14 days, the vast majority of patients reported “less” or “a lot less” usage of oral medications and were very/extremely satisfied with the patch. Results also showed statistically significant and positive outcomes in all measured Quality of Life (QoL) components with improvements in general activity, mood, relations with other people, sleep, normal work, walking ability, and enjoyment of life. In the Control Group, there were no significant changes in pain severity, interference levels, usage of medications, and patient satisfaction was poor during the 14 day study period. Conclusions: Study results indicate that this non-pharmacologic, non-invasive, haptic vibrotactile trigger technology (VTT) embedded topical patch reduces pain severity and interference scores and may reduce the use of concurrent medications, including prescribed anti-inflammatory and other oral medication for adult patients with arthritic, neuropathic, and musculoskeletal pain. Results reported suggest that the non-pharmacological topical pain patch should be added to the current arsenal of noninvasive and nonpharmacological pain therapies.

Enhanced Skin Permeation of 5-Fluorouracil through Drug-in-Adhesive Topical Patches.

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles.

Analysis of the Cost versus Value Associated with the Use of 5 % Lidocaine Topical Patch in Chronic Pain through Patients’ Satisfaction

Analysis of the Cost versus Value Associated with the Use of 5 % Lidocaine Topical Patch in Chronic Pain through Patients’ Satisfaction

Innovative Topical Patches for Non-Melanoma Skin Cancer: Current Challenges and Key Formulation Considerations.

Non-melanoma skin cancer (NMSC) is the most prevalent malignancy worldwide, with approximately 6.3 million new cases worldwide in 2019. One of the key management strategies for NMSC is a topical treatment usually utilised for localised and early-stage disease owing to its non-invasive nature. However, the efficacy of topical agents is often hindered by poor drug penetration and patient adherence. Therefore, various research groups have employed advanced drug delivery systems, including topical patches to overcome the problem of conventional topical treatments. This review begins with an overview of NMSC as well as the current landscape of topical treatments for NMSC, specifically focusing on the emerging technology of topical patches. A detailed discussion of their potential to overcome the limitations of existing therapies will then follow. Most importantly, to the best of our knowledge, this work unprecedentedly combines and discusses all the current advancements in innovative topical patches for the treatment of NMSC. In addition to this, the authors present our insights into the key considerations and emerging trends in the construction of these advanced topical patches. This review is meant for researchers and clinicians to consider utilising advanced topical patch systems in research and clinical trials toward localised interventions of NMSC.

Preparation and characterization of polymeric cross-linked hydrogel patch for topical delivery of gentamicin

Abstract This research aimed to prepare and characterize a new type of polymeric cross-linked topical hydrogel patches for the treatment of wound infections. The free radical polymerization method was used to prepare the topical hydrogel patches by utilizing natural polymers, i.e., agarose and gelatin. These natural polymers were chemically cross-linked with monomer (acrylic acid) using ammonium persulfate as an initiator via the cross-linker N,N methylene bisacrylamide. An antibiotic, i.e., gentamicin sulfate was loaded into a designed polymeric system. The polymeric cross-linked topical hydrogel patches were made in a spherical shape, which was revealed to be stable and elastic. Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray powder diffraction investigation were used to characterize the topical hydrogel patches. Polymeric cross-linked hydrogel patches were evaluated for their sol–gel analysis, swelling studies, in vitro drug release studies against pH 5.5, 6.5, and 7.4, ex vivo drug permeation, and the deposition study on the rabbit’s skin by using a Franz diffusion cell. In addition, the skin irritation study and wound healing performance of drug-loaded topical patches were also assessed and compared to commercially available formulations. The topical hydrogel patches were found to be non-irritating to the skin for up to 72 h as determined by a Draize patch test and when compared to marketed formulations, these topical patches resulted in faster wound healing. The prepared formulation showed promising potential for the treatment of skin wound infection.

In Vitro Release Kinetics of Nystatin and Tannic Acid in Artificial Body Fluids from Hydrogels Prepared by Using Polyvinylpyrrolidone Crosslinked with Tannic Acid

AbstractBiocompatible hydrogels of polyvinylpyrrolidone (PVP) with tannic acid (TA) in the weight ratios of 1 : 0.70 (70 %)–1 : 0.60 (60 %) were prepared and loaded with the antifungal drug, nystatin (NYS). The hydrogel is expected to exhibit a two‐fold (anti‐bacterial and anti‐fungal) characteristics. Infrared spectroscopy (IR), viscometry and differential scanning calorimetry (DSC) were used to investigate interactions between PVP and TA. In vitro release kinetics of NYS in simulated body fluid (SBF) and sweat (SS) were studied using ultra‐violet spectroscopy (UV) and high‐performance liquid chromatography (HPLC). An increase in the glass transition temperature (Tg) of PVP accompanied with changes observed in the OH stretching, C=O and the C−O−C regions in the IR spectrum in dried PVP/TA hydrogel suggested physical crosslinking. The swelling of the hydrogels in distilled deionized water (DDW), SBF and SS decreased with increasing TA concentration and showed pH sensitivity. TA release followed the Korsmeyer‐Peppas kinetic model regardless of swelling media while NYS followed the Korsmeyer‐Peppas and Hixson‐Crowell cube root law in SS and SBF respectively. TA was active against Escherichia coli and Staphylococcus aureus while NYS against Candida albicans. A topical patch was prepared by adhering the drug loaded PVP/TA hydrogel onto silicone strips.

Flexible Topical Hydrogel Patch Loaded with Antimicrobial Drug for Accelerated Wound Healing.

A hydrogel topical patch of neomycin was developed by using sodium alginate (SA) and hydroxyethylcellulose (HEC) as polymers. Free radical polymerization in an aqueous medium was initiated by using acrylic acid (AA) and N,N'-methylenebisacrylamide (MBA). Prepared hydrogels were characterized for pH sensitivity and sol-gel analysis. In addition, the effect of reactant contents on the developed formulation was evaluated by swelling behavior. SEM assay showed the rough structure of the hydrogel-based polymeric matrix, which directly enhances the ability to uptake fluid. FTIR spectra revealed the formation of a new polymeric network between reactant contents. TGA and DSC verified that fabricated polymeric patches were more thermodynamically stable than pure components. Gel fractions increased with increases in polymer, monomer, and cross-linker contents. The swelling study showed the pH-dependent swelling behavior of patches at pH 5.5, 6.5, and 7.4. The release pattern of the drug followed zero-order kinetics, with diffusion-controlled drug release patterns according to the Korsmeyer-Peppas (KP) model. Ex vivo studies across excised rabbit skin verified the drug retention in the skin layers. The hydrogel patch effectively healed the wounds produced on the rabbit skin, whereas the formulation showed no sign of irritation on intact skin. Therefore, neomycin hydrogel patches can be a potential candidate for controlled delivery for efficient wound healing.

DEVELOPMENT AND CHARACTERIZATION OF SELF-HEALING TRANSDERMAL PATCH OF LIDOCAINE FOR THE MANAGEMENT OF PAIN

Pain management is a significant challenge due to the side effects associated with commonly prescribed medications like NSAIDs and opioids. Local anesthetics, such as lidocaine, offer an alternative with fewer side effects when formulated in topical patches. Transdermal delivery systems, including heated patches, enhance drug absorption and provide targeted pain relief. This research paper aims to develop and characterize a self-heating transdermal patch of lidocaine for pain management. The drug sample of lidocaine was characterized using UV-visible spectrophotometric analysis, melting point determination, and differential scanning calorimetry. The results confirmed the purity of the drug sample. Pre-formulation studies were conducted to determine the solubility and partition coefficient of lidocaine, as well as drug-excipient interaction studies. The formulation of the lidocaine transdermal patch included the selection of excipients such as solvents, adhesives, solubilizers, and permeation enhancers. The patch was developed in three trial batches, with the final batch prepared using a drug-in-adhesive type approach. The developed patch was evaluated for physical characteristics, solvent residual content, rolling ball test, shear strength, drug crystallization, drug content, and in-vitro permeation. The results of the evaluation showed that the developed lidocaine transdermal patch had the desired physical characteristics, uniform thickness, good folding endurance, and appropriate solvent residual content. It exhibited satisfactory rolling ball test and shear strength. Microscopic examination confirmed the absence of drug crystallization. The drug content of the patch was determined to be within the desired range, and the in-vitro permeation study demonstrated successful drug release through the dialysis membrane. In conclusion, the development and characterization of a self-heating transdermal patch of lidocaine for pain management provide a promising approach for effective and targeted pain relief. The patch formulation demonstrated suitable physical properties, drug content, and permeation characteristics, suggesting its potential as an alternative pain management solution. KEYWORDS: Lidocaine, transdermal patch, pain management, self-heating, drug delivery

Improving Sleep and Quality of Life after Use of a Haptic Vibrotactile Trigger Technology, Drug-Free, Topical Patch: Results from the HARMONI Study

Sleep issues are widely prevalent throughout the US and can greatly impact a person’s quality of life while imparting a significant personal and societal burden. Evidence supports the importance of sleep health to overall physical health, behavioral health, wellness, and safety. Several diseases have been identified as having a significant association with sleep disorders and sleep duration, including depression, diabetes, obesity, hypertension, and cardiovascular events. Conventional pharmacological treatments for sleep disorders have been associated with dangerous adverse effects. Identifying effective and safe alternative treatment strategies, including those that are non-invasive and non-pharmacologic and that have reduced and limited side effect profiles, will provide options that may be preferable in how clinicians traditionally treat sleep disorders. There has been research focusing on neuronal pathways and circuits that have been shown to respond to sensory (nociceptive) stimulation. Researchers have shown that these pathways and specific areas of the brain can change in response to external stimuli. Haptic vibrotactile trigger technology (VTT) is designed to target the nociceptive pathways and theorized to disrupt these brain centers. The technology has been incorporated into non-invasive, non-pharmacological topical patches and other routes of delivery. The purpose of this IRB-approved, minimal risk observational study was to evaluate patients’ experiences and/or perceptions and patient response for those who received a haptic vibrotactile trigger technology (VTT) embedded non-pharmacologic, non-invasive, over-the-counter sleep patch (REM Sleep Patch with VTT; Super Patch Company, Srysty Holding Co, Toronto, Canada). Methods: Baseline, 7- and 14-day data were recorded in one hundred thirteen (113) adult subjects (79 females and 34 males) with a mean age of 53 years who presented with sleep- or insomnia- related issues or associated symptoms. The study evaluated changes in overall sleep quality and insomnia severity scores via validated scales (PSQI (Pittsburgh Sleep Quality Index) and the ISI (Insomnia Severity Index)), changes in the use of prescription and OTC medications, patient satisfaction, and any side effects reported while using the patch. Future analysis will compare the outcomes reported here with control and crossover treatment groups. Results: The results showed statistically significant decreases in time to fall asleep, an increase in number of hours of sleep, improvement in the quality of sleep, and reduction in global PSQI Score after using the VTT embedded sleep patch. After 14 days, the vast majority of patients reported a reduction of usage of oral medications, that the patch was convenient and easy to use, and preferred the patch over oral and other medications for sleep. Results also showed positive outcomes in Quality of Life (QoL) components with improvements in daytime fatigue, mood, ability to function at work/daily chores, concentration, memory, and mood. Conclusions: Study results indicate that this non-pharmacologic, non-invasive, haptic vibrotactile trigger technology (VTT) embedded topical patch improves sleep quality, duration, and quality-of-life components and may reduce the use of concurrent medications, including prescribed and other oral medication for adult patients with sleep or insomnia-related symptoms. Results reported suggest that the non-pharmacological topical sleep patch has incredible potential to be added to the current approaches and treatments of noninvasive and nonpharmacological sleep therapies.

Formulation and Characterization of Polymeric Cross-Linked Hydrogel Patches for Topical Delivery of Antibiotic for Healing Wound Infections.

Wound healing faces significant challenges in clinical settings. It often contains a series of dynamic and complex physiological healing processes. Instead of creams, ointments and solutions, alternative treatment approaches are needed. The main objective of the study was to formulate bacitracin zinc-loaded topical patches as a new therapeutic agent for potential wound healing. A free radical polymerization technique was optimized for synthesis. Polyethylene glycol-8000 (PEG-8000) was chemically cross-linked with acrylic acid in aqueous medium, using Carbopol 934 as a permeation enhancer and tween 80 as surfactant. Ammonium persulfate and N,N'-Methylenebisacrylamide (MBA) were utilized as initiator and cross-linker. FTIR, DSC, TGA, and SEM were performed, and patches were evaluated for swelling dynamics, sol-gel analysis, in vitro drug release in various media. A Franz diffusion cell was used for the permeation study. Irritation and wound healing with the drug-loaded patches were also studied. The characterization studies confirmed the formation of a cross-linked hydrogel network. The highest swelling and drug release were observed in formulations containing highest Polyethylene glycol-8000 and lowest N,N'-Methylenebisacrylamide concentrations. The pH-sensitive behavior of patches was also confirmed as more swelling, drug release and drug permeation across skin were observed at pH 7.4. Fabricated patches showed no sign of irritation or erythema as evaluated by the Draize scale. Faster wound healing was also observed with fabricated patches compared to marketed formulations. Therefore, such a polymeric network can be a promising technology for speeding up wound healing and minor skin injuries through enhanced drug deposition.

Analytical Quality by Design (AQBD) Assisted Development and Validation of HPTLC Method for Estimation of Rottlerin in Topical Patch Formulation

Pharmacognosy Research,2023,15,2,267-276.DOI:10.5530/pres.15.2.029Published:February 2023Type:Original Article Authors:Kaumudee Bodas, Vaibhav M Shinde, Deshmukh Vishal, and Deshmukh Sheetal Author(s) affiliations:Kaumudee Bodas1, Vaibhav M Shinde1,*, Deshmukh Vishal2, Deshmukh Sheetal2 1Centre for Advanced Research in Pharmaceutical Sciences, Poona College of Pharmacy, Pune, Maharashtra, INDIA. 2Bharati Vidyapeeth (Deemed to be University), Yashwantrao Mohite Institute of Management, Karad, Maharashtra, INDIA. Abstract:Background: Rottlerin, a natural polyphenolic ketone is a major constituent of Mallotus philippensis (Lam.) Mull. Arg. plant. Although, less explored it has diverse array of therapeutic applications. Objectives: The current work aimed to develop novel, simple, speedy, accurate, potent High Performance Thin Layer Chromatography Method (HPTLC) to separate, and quantify rottlerin from the herbal topical patch In-House formulation. Materials and Methods: This was the foremost attempt to develop and validate HPTLC method using Analytical Quality by design (AQbD) approach. Box Behnken design (BBD) coupled with response surface methodology approach was followed for the systematic optimization. The end results of toluene content, chamber conditioning time, and solvent front on Rf value of rottlerin was studied. The optimised method was validated as per ICH guidelines. Results: For HPTLC, stationary phase used was aluminium plates 60F254 coated with silica gel as. AQbD optimised conditions were mobile phase proportion namely toluene: ethyl acetate: methanol: ammonia (5:4:2:0.2), development distance 80 mm, band width 6mm, and chamber saturation time 10 min. The method generated well resolved and compact bands at Rf of 0.41±0.05. The developed method exhibited high accuracy, precision, robustness, and recovery. The quantity of Rottlerin in developed herbal patch was found to be 134.8 ng/band. Conclusion: In a nutshell, the present study undeniably vouches for a QbD based method development approach for Rottlerin and can be extrapolated to estimate it in other herbal extracts, or marketed formulations Keywords:Analytical Quality by design (AQbD), HPTLC, Mallotus philippensis (Lam.) Mull. Arg., Rottlerin, Topical patch.View:PDF (1.15 MB)

DoE-based formulation, physicochemical properties, and anti-inflammatory investigation of a topical patch preparing by partially neutralized polyacrylate-based adhesive hydrogel

A capsaicin patch was formulated by optimizing the adhesion, the release behavior of the patch, and the pharmacological effect. The aims of study were to 1) apply the design of experiments approach for investigating the simultaneous effect of Viscomate (partially neutralized polyacrylate)-based adhesive, glycerin plasticizing excipient and permeation enhancers on patch adhesion, and the permeation rate of model drug (capsaicin) and then 2) compare the optimal formulation with the reference product (Wellpatch®, Metholatum, U.S.A.) in terms of pharmacological effect. The topical patch was prepared by casting the drug-loaded adhesive hydrogel on the backing layer. The adhesive ability of patches was determined by testing a 90° peel rig on a texture analyzer, and the permeation rate of capsaicin (CAP) through mouse skin was evaluated using Franz diffusion cells. The effects of these critical factors on patch adhesion, CAP flux, and permeation enhancer interaction with the stratum corneum were analyzed using ANOVA and ATR-FTIR/skin hydration tests, respectively. Accordingly, Viscomate (adhesion excipient) and glycerin (plasticizing excipient) had a significant impact on patch adhesion (p < 0.05). Meanwhile, N-methyl pyrrolidone, the permeation enhancer, had a better permeation rate and higher hydration level of the stratum corneum than did Transcutol. The partially neutralized polyacrylate-based optimal formulation had a higher permeation rate of CAP, equal adhesion and comparable anti-inflammatory effects to those of the reference product which was also in agreement with the analysis of anatomical images of tissue structure and inflammatory cells. This study successfully integrated DoE method, release behavior and pharmacological research to develop a stable and highly effective topical product containing capsaicin.

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach.

Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. In this study, stearyl alcohol, oleic acid, Tween® 80 (polysorbate 80), and Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm2 and 12.3 ± 2.2 µg/cm2, while the commercial cream only deposited 1.0 ± 0.8 µg/cm2 and 1.5 ± 0.5 µg/cm2 of IMQ, respectively. In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.

Haptic Vibrotactile Trigger Technology: Disrupting the Neuromatrix to Reduce Pain Severity and Interference: Results from the HARMONI Study

The prevalence of pain and pain-related diseases are so vast that they are the leading causes of disability and disease burden across the globe. Over 100 million people are estimated to live with chronic or recurrent pain in the United States and it is the most common reason patients consult primary care clinicians. Conventional pharmacological treatments for pain have been associated with dangerous adverse effects. Identifying effective, alternative treatment strategies, including those that are non-invasive and non-pharmacologic and that have reduced and limited side effect profiles, will provide options that may be preferable in how clinicians traditionally treat pain. Understanding the pain neuromatrix may assist in identifying these alternative approaches that reduce pain severity and interference, and that improve patient outcomes. The neuromatrix of pain is a network of neuronal pathways and circuits responding to sensory (nociceptive) stimulation. Researchers have shown that these pathways and areas of the brain that are associated with the neuromatrix can change in response to external stimuli. Haptic vibrotactile trigger technology (VTT) is designed to target the nociceptive pathways and theorized to disrupt the neuromatrix of pain. The technology has been incorporated into non-invasive, non-pharmacological topical patches and other routes of delivery. The purpose of this IRB-approved, minimal risk study was to evaluate patients’ experiences and/or perceptions and patient response for those who received a haptic vibrotactile trigger technology (VTT) embedded non-pharmacologic, non-invasive, over-the-counter pain patch (FREEDOM Super Patch with VTT; Srysty Holding Co, Toronto, Canada). Methods: Baseline, 7- and 14-day data were recorded in one hundred forty-eight (148) adult subjects (96 females and 52 males) with a mean age of 53 years who presented with mild, moderate and even severe musculoskeletal, arthritic and neurological pain. The study evaluated changes in overall severity and interference scores via a validated scale (Brief Pain Inventory (BPI)), changes in the use of prescription and OTC medications, patient satisfaction, and any side effects reported while using the patch. Future analyses will compare the outcomes reported here with non-active control and crossover treatment groups. Results: The results showed statistically significant decreases in mean BPI severity and interference scores after using the VTT embedded pain patch. After 14 days, the vast majority of patients reported “less” or “a lot less” usage of oral medications and were very/extremely satisfied with the patch. Results also showed statistically significant and positive outcomes in all measured Quality of Life (QoL) components with improvements in general activity, mood, relations with other people, sleep, normal work, walking ability, and enjoyment of life. Conclusions: Study results indicate that this non-pharmacologic, non-invasive, haptic vibrotactile trigger technology (VTT) embedded topical patch reduces pain severity and interference scores and may reduce the use of concurrent medications, including prescribed anti-inflammatory and other oral medication for adult patients with arthritic, neuropathic, and musculoskeletal pain. Results reported suggest that the non-pharmacological topical pain patch has incredible potential to be added to the current arsenal of noninvasive and nonpharmacological pain therapies.

New vegetable-waste biomaterials by Lupin albus L. as cellular scaffolds for applications in biomedicine and food

The reprocessing of vegetal-waste represents a new research field in order to design novel biomaterials for potential biomedical applications and in food industry. Here we obtained a biomaterial from Lupinus albus L. hull (LH) that was characterized micro-structurally by scanning electron microscopy and for its antimicrobial and scaffolding properties. A good adhesion and proliferation of human mesenchymal stem cells (hMSCs) seeded on LH scaffold were observed. Thanks to its high content of cellulose and beneficial phytochemical substances, LH and its derivatives can represent an available source for fabrication of biocompatible and bioactive scaffolds. Therefore, a reprocessing protocol of LH was optimized for producing a new LH bioplastic named BPLH. This new biomaterial was characterized by chemico-physical analyses. The water uptake, degradability and antimicrobial properties of BPLH were evaluated, as well as the mechanical properties. A good adhesion and proliferation of both fibroblasts and hMSCs on BPLH were observed over 2 weeks, and immunofluorescence analysis of hMSCs after 3 weeks indicates an initial commitment toward muscle differentiation. Our work represents a new approach toward the recovery and valorization of the vegetal waste showing the remarkable properties of LH and BPLH as cellular waste-based scaffold with potential applications in cell-based food field as well as in medicine for topical patches in wound healing and bedsores treatment.

Development and Characterisation of a Topical Methyl Salicylate Patch: Effect of Solvents on Adhesion and Skin Permeation.

The advent of skin patch formulation design and technology has enabled the commercialisation of methyl salicylate (MS) as a topical patch. However, the most fundamental aspect of skin permeation is unknown at present. The study aims to investigate the effect of solvent choice on the skin permeation of MS in a neat solvent system and patch formulation with an emphasis on patch adhesion. MS in six selected solvents (propylene glycol (PG), Transcutol®, isopropyl myristate, Labrasol®, Plurol® oleique CC 497 and Maisine® CC) was characterised and in vitro permeation studies were also performed. An ATR-FTIR analysis on solvent-treated skin was conudcted. Patch formulation was prepared and characterised for adhesion, in vitro drug release and skin permeation studies. The highest MS permeation was found in neat PG over 24 h (~90 μg/cm2) due to its strong skin protein conformation effect. Transcutol® and isopropyl myristate showed better skin deposition and formulation retention, respectively. Nevertheless, PG enhanced the patch adhesion despite having a lower cumulative amount of MS permeated (~80 μg/cm2) as compared with Transcutol® and Maisine® (~110-150 μg/cm2). These two solvents, however, demonstrated better skin deposition and formulation retention but a lower patch adhesion. The unpredictable influence of the solvent on patch adhesion highlights the importance of the trade-off between patch adhesion and skin permeation during formulation design.

(Almost) Everything You Always Wanted to Know About Cannabis Science, but Were Afraid to Ask!

Aim: It is estimated that approximately 25% of cancer patients are currently taking cannabis to alleviate symptoms of their disease and/or cope with the side effects of their treatment. Patients want to learn more about cannabis from their cancer healthcare team, but most Radiation Therapists (RTs) feel too uninformed to discuss this subject. The purpose of this abstract is to provide information about cannabis that is relevant and useful for RTs. Process: Cannabis is a broad term used to describe organic products derived from the Cannabis plant. The unique group of active chemical compounds found in cannabis are called cannabinoids. Among the more than 100 different types of cannabinoids, the most abundant and well-studied are delta9 tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the primary intoxicating compound of cannabis, which is responsible the euphoric “high”. CBD is a non-intoxicating constituent of cannabis. Terpenes are the third most prevalent compound in cannabis, these give cannabis its distinctive fragrance. Plants are selectively bred to produce particular THC/CBD ratios, and there are more than 200 medical strains currently available from licensed producers in Canada. Cannabis comes in many forms, including dried flower, processed oil, pharmaceutical grade pills and topical patches. Cannabis can be ingested by inhalation, orally, sublingually and topically. Each of these methods has its own rate of onset and duration of effects, and differences in the bioavailability of cannabinoids. Cannabinoids are absorbed into the blood, then rapidly distributed into the brain and other high perfusion tissues. They are then metabolized by CYP liver enzymes and eventually eliminated via feces or urine. All forms of cannabinoids work on the endocannabinoid system within the human body, which consists of a series of neuromodulators and their associated receptors located throughout the brain, peripheral nervous system and immune system. Benefits/Challenges: Cancer patients most frequently take cannabis to improve nausea and appetite, pain, stress and sleep, with 51% - 83% self-reporting a major benefit. The Canadian Cannabis Act (2018) provides access to cannabis for those over 18yrs via medical cannabis programs, prescription pharmaceuticals, pharmacies, provincial websites and retail storefronts. Despite widespread availability, there are multiple precautions and contraindications when considering taking cannabis. These include patient risk factors (e.g. schizophrenia, cardio-metabolic disorders, respiratory conditions), drug-on-drug interactions (e.g. anti-coagulants, statins, SSRIs), lifestyle risk factors (e.g. driving, working, travelling) and the development of a use disorder. Short term harms associated with cannabis use include impaired cognitive and motor function, tachycardia, anxiety and paranoia. Long term harms include impaired learning and memory and development of chronic bronchitis. Evidence-based guidelines are now available to lower the risks associated with taking cannabis. Impact/Outcomes Most RTs have little knowledge about the therapeutic use of cannabis by cancer patients, and <15% of patients receive any information about cannabis from their healthcare team. This leaves our patients exposed to cannabis myths and misrepresentations found during internet searches. Educational opportunities are urgently needed to provide RTs with information about the science of cannabis so they can support and advise their patients.