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The Journal of Clinical and Aesthetic... May 2023Topical therapies remain the mainstay in treating patients with acne and rosacea. However, emerging real-world evidence demonstrates that desired treatment outcomes... (Review)
Review
OBJECTIVE
Topical therapies remain the mainstay in treating patients with acne and rosacea. However, emerging real-world evidence demonstrates that desired treatment outcomes might not be achieved if patient satisfaction and adherence are low. Poor tolerability of active drug(s) and vehicle components and/or the drug delivery system could negatively influence adherence. Additionally, adherence might be lower with complex treatment regimens involving the application of multiple topical formulations. Optimizing vehicle tolerability and simplifying regimens that use fixed-dose combinations may improve treatment outcomes, better patient satisfaction, and reduce overall treatment costs. This qualitative review discusses several innovative drug delivery technologies and formulations aimed at improving patient satisfaction and adherence.
METHODS
The authors conducted a search of current and emerging topical drug delivery technologies used in clinical studies, reviewed primary literature on the chemical characteristics of topical dosage forms, and compared the impacts on treatment outcomes for acne and rosacea.
RESULTS
This article provides insight into innovative vehicles and drug delivery systems that have emerged allowing for fixed-dose combinations of incompatible active drugs and improving the tolerability of historically irritative active ingredients.
LIMITATIONS
Further research is needed to fully highlight the impact of patient satisfaction and modern topical formulations on adherence and treatment outcomes.
CONCLUSION
Drug microencapsulation is a delivery technology that has enabled development of a topical fixed-dose combination of benzoyl peroxide and tretinoin preventing the oxidation of tretinoin by benzoyl peroxide and improving the tolerability of the active ingredients.
PubMed: 37288283
DOI: No ID Found -
Pain Apr 2023Opioid-involved motor vehicle traffic fatalities have increased over the past 2 decades. However, the extent to which prescribed opioids increase the risk of motor...
Opioid-involved motor vehicle traffic fatalities have increased over the past 2 decades. However, the extent to which prescribed opioids increase the risk of motor vehicle crashes remains uncertain. This study used real-world healthcare claims data to examine the association between prescription opioid dose and motor vehicle crash risk. Using nationwide US commercial insurance claims data for 2010 to 2018, we identified 772,404 adults who received incident, noncancer opioid therapy. We examined associations between daily prescription opioid dose, calculated in morphine milligram equivalents (MME) from filled prescription claims, and risk of motor vehicle crashes, assessed as diagnoses of motor vehicle injuries in claims for emergency visits, inpatient hospitalizations, and ambulance transportation. We estimated associations using a within-individual design, which ruled out all time-stable confounding. We complemented the design with time-varying statistical adjustment for other pharmacotherapies and a negative control pain pharmacotherapy analysis (with incident cyclic antidepressant prescriptions). During 2,150,009 person-years of follow-up, there were 12,123 motor vehicle crashes (5.64 crashes per 1000 person-years). In within-individual comparisons, crash risk was greater during opioid prescription periods involving doses ≤60 MME/day (odds ratio [OR], 3.86; 95% confidence interval [CI], 3.54, 4.21), >60 to 120 MME/day (OR, 5.46; 95% CI, 4.44, 6.73), and >120 MME/day (OR, 3.45; 95% CI, 2.31, 5.15) than during off-treatment periods. The negative control analysis supported the specificity of the results to opioids rather than to other processes associated with pharmacologic pain management. These findings suggest that the receipt of prescription opioids, even at doses ≤60 MME/day, is associated with an increased risk of motor vehicle crashes.
Topics: Adult; Humans; Analgesics, Opioid; Accidents, Traffic; Prescriptions; Motor Vehicles; Practice Patterns, Physicians'; Pain; Retrospective Studies
PubMed: 36155384
DOI: 10.1097/j.pain.0000000000002790 -
Skin Therapy Letter Jul 2018Most people with mild-to-moderate psoriasis manage their disease with topical therapies. However, adherence to topical treatment remains a challenge, as the daily... (Review)
Review
Most people with mild-to-moderate psoriasis manage their disease with topical therapies. However, adherence to topical treatment remains a challenge, as the daily application creates a significant treatment burden. New topical therapeutic options need to offer higher efficacy and better patient acceptability, including easier application, to reduce treatment burden and enhance patient adherence. Topical foam vehicles are innovative alternatives to creams and ointments, addressing many patient challenges with traditional vehicles. Well-designed foam vehicles are easily spread over large areas of the skin, while importantly not leaving a greasy or oily film on the skin after application. Calcipotriol/betamethasone diproprionate aerosol foam is a new psoriasis treatment option that is rapidly effective, offers greater efficacy versus ointment and gel formulations, and has been shown to increase patient treatment satisfaction. Hence, by addressing the several crucial unmet clinical needs in patients with mild-to-moderate psoriasis, this optimized foam formulation is poised to improve treatment follow-through.
Topics: Administration, Cutaneous; Aerosols; Betamethasone; Calcitriol; Dermatologic Agents; Drug Combinations; Humans; Psoriasis; Randomized Controlled Trials as Topic
PubMed: 30086183
DOI: No ID Found -
Frontiers in Immunology 2023The long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic... (Review)
Review
The long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main drug delivery dilemmas. On the one side, the versatility of the vehicle to efficiently load, protect and transport the drug and then release it at the target place. On the other hand, the questions related to the degree of PEGylation which are needed to avoid nanoparticle (NP) aggregation and opsonization while preventing cellular uptake. The development of different kinds of lipidic drug delivery vehicles and particles has resulted in the development of ionizable lipid nanoparticles (iLNPs), which can overcome most of the typical drug delivery problems. Proof of their success is the late approval and massive administration as the prophylactic vaccine for SARS-CoV-2. These ILNPs are built by electrostatic aggregation of surfactants, the therapeutic agent, and lipids that self-segregate from an aqueous solution, forming nanoparticles stabilized with lipid polymers, such as PEG. These vehicles overcome previous limitations such as low loading and high toxicity, likely thanks to low charge at the working pH and reduced size, and their entry into the cells endocytosis rather than membrane perforation or fusion, always associated with higher toxicity. We herein revise their primary features, synthetic methods to prepare and characterize them, pharmacokinetic (administration, distribution, metabolization and excretion) aspects, and biodistribution and fate. Owing to their advantages, iLNPs are potential drug delivery systems to improve the management of various diseases and widely available for clinical use.
Topics: Humans; Surface-Active Agents; RNA; Tissue Distribution; COVID-19 Vaccines; Lipids; COVID-19; SARS-CoV-2; Nanoparticles; Lipoproteins; Pulmonary Surfactants
PubMed: 36923400
DOI: 10.3389/fimmu.2023.1129296 -
ACS Omega Dec 2023An impaired immune system is the root of various human ailments provoking the urge to find vehicle-mediated quick delivery of small drug molecules and other vital... (Review)
Review
An impaired immune system is the root of various human ailments provoking the urge to find vehicle-mediated quick delivery of small drug molecules and other vital metabolites to specific tissues and organs. Thus, drug delivery strategies are in need of improvement in therapeutic efficacy. It can be achieved only by increasing the drug-loading capacity, increasing the sustained release of a drug to its target site, easy relocation of drug molecules associated with facile complexation-induced properties of molecular vehicles, and high stimuli-responsive drug administration. Supramolecular drug delivery systems (SDDS) provide a much needed robust yet facile platform for fabricating innovative drug nanocarriers assembled by thermodynamically noncovalent interaction with the tunable framework and above-mentioned properties. Measures of cytotoxicity and biocompatibility are the two main criteria that lie at the root of any promising medicinal applications. This Review features significant advancements in (i) supramolecular host-guest complexation using cucurbit[7]uril (CB[7]), (ii) encapsulation of the drug and its delivery application tailored for CB[7], (iii) self-assembly of supramolecular amphiphiles, (iv) supramolecular guest relay using host-protein nanocavities, (v) pillararene (a unique macrocyclic host)-mediated SDDS for the delivery of smart nanodrugs for siRNA, fluorescent molecules, and insulin for juvenile diabetes. Furthermore, fundamental questions and future hurdles related to smart SDDS based on CB[7] and pillararenes and their future promising breakthrough implementations are also distinctly outlined in this Review.
PubMed: 38144095
DOI: 10.1021/acsomega.3c05465 -
Actas Dermo-sifiliograficas Apr 2021The administration of appropriate doses of active ingredients and excipients is crucial for achieving desired treatment outcomes in pediatric dermatology. A number of... (Review)
Review
The administration of appropriate doses of active ingredients and excipients is crucial for achieving desired treatment outcomes in pediatric dermatology. A number of factors need to be considered, including the characteristics of the lesion, the patient, and the drug. An additional challenge in pediatric settings is the limited number of commercially available formulations suitable for use in children. Drug compounding, which is the preparation of medications tailored to the needs of individual patients, is a good alternative for pediatric populations for a number of reasons. Using a customized compound, the clinician can prescribe formulations that contain the optimal dose of the active ingredients within acceptable limits and the most suitable vehicle and formulation components. Compounding can also be used to combine several active ingredients in a single medication and even adapt the vehicle to the characteristics of the lesion and the needs of the patient. The pharmaceutical formulations described in this review are based on extensive clinical experience and can be customized to meet individual needs.
Topics: Adaptation, Physiological; Child; Dermatology; Drug Compounding; Excipients; Humans; Pharmaceutical Preparations
PubMed: 33220314
DOI: 10.1016/j.ad.2020.11.006 -
AAPS PharmSciTech Nov 2018A heightened interest in (trans)dermal delivery is in part driven by the need to improve the existing skin therapies and also the demand for alternative routes of... (Review)
Review
A heightened interest in (trans)dermal delivery is in part driven by the need to improve the existing skin therapies and also the demand for alternative routes of administration, notably for pharmaceutical actives with undesirable oral absorption characteristics. The premise of delivering difficult actives to the skin or via the skin however is weighed down by the barrier function properties of the stratum corneum. Short of disrupting the skin by physical means, scientists have resorted to formulation with excipients known to enhance the skin penetration and permeation of drugs. A vehicle that has emerged over the years as a safe solubilizer and enhancer for a broad range of drug actives is the highly purified NF/EP grade of diethylene glycol monoethyl ether (DEGEE) commercially known as Transcutol®. Whereas numerous studies affirm its enhancing effect on drug solubilization, percutaneous absorption rate, and/or drug retention in the skin, there are few publications that unite the body of the published literature in describing the precise role and mechanisms of action for Transcutol®. In view of the current mechanistic understanding of skin barrier properties, this paper takes on a retrospective review of the published works and critically evaluates the data for potential misses due to experimental variables such as formulation design, skin model, skin hydration levels, and drug properties. The goal of this review is to mitigate the incongruence of the published works and to construct a unified, comprehensive understanding of how Transcutol® influences skin penetration and permeation. Graphical Abstract Transcutol has affinity for the hydrophilic head groups of the stratum corneum structures.
Topics: Administration, Cutaneous; Animals; Ethylene Glycols; Permeability; Pharmaceutical Vehicles; Retrospective Studies; Skin; Skin Absorption
PubMed: 30421383
DOI: 10.1208/s12249-018-1196-8 -
Advanced Drug Delivery Reviews Jul 2023Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and... (Review)
Review
Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and physiological barriers while minimising tissue toxicity has restricted developments in this field. Aqueous vehicles have traditionally been used, which typically require several additives and preservatives to achieve physiologically compatible and sterile eyedrops, elevating their toxicity potential. Non-aqueous vehicles have been suggested as efficient alternatives for topical drug delivery as they can address many of the limitations associated with conventional aqueous eyedrops. However, despite their obvious advantages, non-aqueous eyedrops remain poorly researched and few non-aqueous formulations are currently available in the market. This review challenges the conventional hypothesis that aqueous solubility is a prerequisite to ocular drug absorption and establishes a rationale for using non-aqueous vehicles for ocular drug delivery. Recent advances in the field have been detailed and future research prospects have been explored, pointing towards a paradigm shift in eyedrop formulation in the near future.
Topics: Humans; Administration, Topical; Eye; Drug Delivery Systems; Ophthalmic Solutions
PubMed: 37178927
DOI: 10.1016/j.addr.2023.114867 -
AAPS PharmSciTech Mar 2011Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth... (Review)
Review
Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.
Topics: Administration, Oral; Antineoplastic Agents; Colon; Colonic Neoplasms; Drug Carriers; Drug Delivery Systems; Humans; Pectins; Pharmaceutical Vehicles
PubMed: 21194013
DOI: 10.1208/s12249-010-9564-z -
Pharmaceutics May 2023Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs)... (Review)
Review
Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs) seem to be one of the central mediators of the therapeutic functions of MSCs. MSC-EVs are membrane structures secreted by the MSCs, rich in specific proteins, lipids, and nucleic acids. Amongst these, microRNAs have achieved the most attention currently. Unmodified MSC-EVs can promote or inhibit tumor growth, while modified MSC-EVs are involved in the suppression of cancer progression via the delivery of therapeutic molecules, including miRNAs, specific siRNAs, or suicide RNAs, as well as chemotherapeutic drugs. Here, we present an overview of the characteristics of the MSCs-EVs and describe the current methods for their isolation and analysis, the content of their cargo, and modalities for the modification of MSC-EVs in order for them to be used as drug delivery vehicles. Finally, we describe different roles of MSC-EVs in the tumor microenvironment and summarize current advances of MCS-EVs in cancer research and therapy. MSC-EVs are expected to be a novel and promising cell-free therapeutic drug delivery vehicle for the treatment of cancer.
PubMed: 37242693
DOI: 10.3390/pharmaceutics15051453