Transdermal Research Articles

5158 Estrogen for Feminizing Gender Affirming Hormone Therapy: Understanding the Influence of Route of Administration and Dose on Serum Estradiol and Testosterone Levels

Abstract Disclosure: D.J. Slack: None. A. Di Via Ioschpe: None. M. Saturno: None. S. Kihuwa-Mani: None. U. Amakiri: None. S. Karim: None. D. Guerra: None. J.D. Safer: None. For feminizing gender affirming hormone therapy (GAHT), the Endocrine Society and WPATH SOC 8 suggest targeting testosterone (T) levels below 50 ng/dL and estradiol (E2) levels in the range of 100-200 pg/mL. Exogenous estrogen may be given via several routes of administration (ROA) and at a variety of doses, but little is known about how ROA and dose influence T and E2 levels. We sought to investigate the relationship between estrogen dosage, ROA, and hormonal profiles in trans feminine individuals. We conducted a chart review of patients in the Mount Sinai Health System and included all patients who had active prescriptions for feminizing GAHT with both T and E2 levels recorded (n = 585), excluding those with a history of orchiectomy. For oral (PO) estrogen, there was a negative correlation between dose and serum T (p < .01), LH (p < .05), and FSH (p < .05), but no correlation with E2. For transdermal (TD) estrogen, dose did not correlate with serum T, E2, LH, or FSH. For intramuscular (IM) estrogen, there was a positive correlation with serum E2 (p < .05), LH (p < .05), and FSH (p < .01), but no correlation with T. Individuals were then stratified into groups of T and E2 ranges that were determined via bell-curve frequency distributions. Within each group, the relative proportion of users of a given ROA, their mean dose of estrogen given via that ROA, and their resulting mean T and E2 levels were calculated. For users of IM estrogen, a significantly higher proportion of individuals had T < 50 ng/dL as opposed to T >= 50 ng/dL. IM users also much more frequently exhibited E2 >= 200 pg/mL than E2 < 200 pg/mL. For users of PO estrogen, a higher proportion of individuals had T >= 100 ng/dL compared to T < 50 ng/dL, with the proportion of those with T 50-99 ng/dL not differing from either group. A higher proportion of users of PO estrogen had E2 50 - 199 pg/mL compared to E2 < 25 ng/dL and E2 > 200 pg/mL, with the proportion of those with E2 25-49 pg/mL not differing significantly from either. For users of TD estrogen, there was a higher proportion of those with T 50 - 99 ng/dL compared to < 50 ng/dL and >= 200 ng/dL, with the proportion of those with T 100 - 199 ng/dL not differing from either group. A higher proportion of users of TD estrogen had E2 25 - 49 pg/mL compared to E2 100 - 199 pg/mL and E2 > 300 pg/mL, while the frequency of those with E2 < 25 pg/mL, 50 - 99 pg/mL, or 200 - 299 pg/mL did not differ significantly. Our results indicate a propensity for users of IM estrogen to achieve T suppression and to overshoot E2 targets, while users of PO estrogen were most likely to have E2 levels at-target but less likely to achieve T suppression. Users of TD estrogen appear least likely to achieve either target. While further research is needed to confirm and expand upon our findings, our data are an important step forward in providing clinicians with some predictive capability as to the serum E2 and T levels they might expect with the use of exogenous estrogen at a given dose and ROA. Presentation: 6/2/2024

5158 Estrogen for Feminizing Gender Affirming Hormone Therapy: Understanding the Influence of Route of Administration and Dose on Serum Estradiol and Testosterone Levels

Abstract Disclosure: D.J. Slack: None. A. Di Via Ioschpe: None. M. Saturno: None. S. Kihuwa-Mani: None. U. Amakiri: None. S. Karim: None. D. Guerra: None. J.D. Safer: None. For feminizing gender affirming hormone therapy (GAHT), the Endocrine Society and WPATH SOC 8 suggest targeting testosterone (T) levels below 50 ng/dL and estradiol (E2) levels in the range of 100-200 pg/mL. Exogenous estrogen may be given via several routes of administration (ROA) and at a variety of doses, but little is known about how ROA and dose influence T and E2 levels. We sought to investigate the relationship between estrogen dosage, ROA, and hormonal profiles in trans feminine individuals. We conducted a chart review of patients in the Mount Sinai Health System and included all patients who had active prescriptions for feminizing GAHT with both T and E2 levels recorded (n = 585), excluding those with a history of orchiectomy. For oral (PO) estrogen, there was a negative correlation between dose and serum T (p < .01), LH (p < .05), and FSH (p < .05), but no correlation with E2. For transdermal (TD) estrogen, dose did not correlate with serum T, E2, LH, or FSH. For intramuscular (IM) estrogen, there was a positive correlation with serum E2 (p < .05), LH (p < .05), and FSH (p < .01), but no correlation with T. Individuals were then stratified into groups of T and E2 ranges that were determined via bell-curve frequency distributions. Within each group, the relative proportion of users of a given ROA, their mean dose of estrogen given via that ROA, and their resulting mean T and E2 levels were calculated. For users of IM estrogen, a significantly higher proportion of individuals had T < 50 ng/dL as opposed to T >= 50 ng/dL. IM users also much more frequently exhibited E2 >= 200 pg/mL than E2 < 200 pg/mL. For users of PO estrogen, a higher proportion of individuals had T >= 100 ng/dL compared to T < 50 ng/dL, with the proportion of those with T 50-99 ng/dL not differing from either group. A higher proportion of users of PO estrogen had E2 50 - 199 pg/mL compared to E2 < 25 ng/dL and E2 > 200 pg/mL, with the proportion of those with E2 25-49 pg/mL not differing significantly from either. For users of TD estrogen, there was a higher proportion of those with T 50 - 99 ng/dL compared to < 50 ng/dL and >= 200 ng/dL, with the proportion of those with T 100 - 199 ng/dL not differing from either group. A higher proportion of users of TD estrogen had E2 25 - 49 pg/mL compared to E2 100 - 199 pg/mL and E2 > 300 pg/mL, while the frequency of those with E2 < 25 pg/mL, 50 - 99 pg/mL, or 200 - 299 pg/mL did not differ significantly. Our results indicate a propensity for users of IM estrogen to achieve T suppression and to overshoot E2 targets, while users of PO estrogen were most likely to have E2 levels at-target but less likely to achieve T suppression. Users of TD estrogen appear least likely to achieve either target. While further research is needed to confirm and expand upon our findings, our data are an important step forward in providing clinicians with some predictive capability as to the serum E2 and T levels they might expect with the use of exogenous estrogen at a given dose and ROA. Presentation: 6/2/2024

Transdermal Drug Delivery Systems (TDDS): Recent Advances and Failure Modes.

Transdermal drug delivery systems (TDDS), commonly refered to as "patches", present a nonintrusive technique to provide medication without the need for invasive procedures. These products adhere to the skin and gradually release a specific dosage of medicine at a defined rate into the bloodstream. Compared with other methods of drug delivery, TDDS offer benefits such as reduced invasiveness, convenience for patients, and avoidance of the metabolic processes that occur when drugs are orally consumed. Throughout time, TDDS have been used to provide medications for various medical conditions (such as nicotine, fentanyl, nitroglycerin, and clonidine), and their potential for delivering biologics is currently being explored. This review investigates the current literature on the drug delivery efficacy of medical TDDS through the transdermal route. Additionally, the review addresses potential risks and failure modes associated with TDDS design and development as well as strategies for mitigating such risks. A thorough understanding of failure modes provides a blueprint to mitigate failure and produce high-quality efficacious therapeutics.

Examining the Influence of the Route of Administration and Dose of Estradiol on Serum Estradiol and Testosterone Levels in Feminizing Gender-Affirming Hormone Therapy

IntroductionIndividuals may seek gender-affirming hormone therapy (GAHT) to align their physical appearance with their gender identity. Feminizing GAHT typically involves the use of estrogen. This study investigates the effect of route of administration (ROA) and dose of estradiol on estradiol (E2) and testosterone (T) levels in transfeminine individuals. MethodsWe conducted a chart review of 573 patients with an active prescription for estradiol for feminizing GAHT and serum hormone levels available. Multiple linear regression and analysis of variance were used to analyze the effect of dose and ROA of estradiol on serum E2 and T. ResultsOral estradiol was the only ROA demonstrating a linear dose-response, with each 1 mg/d increase associated with a reduction in T of 19.03 ng/dL (P = .005). Lower T levels were seen with higher doses of transdermal estradiol but a significant dose-response was not demonstrated. Intramuscular estradiol was associated with lower T and higher E2 compared to oral and transdermal ROAs (P < .001), with many achieving target hormone levels even at low doses. Higher doses of oral estradiol were associated with lower mean serum leutenizing hormone and follicle stimulating hormone levels (P < .05). ConclusionOral estradiol can be titrated to achieve a stepwise decrease in serum T. The intramuscular ROA appears to be the most potent delivery of estradiol with impact on serum hormone levels with doses on the low end of guideline-suggested ranges. Serum leutenizing hormone and follicle stimulating hormone may also help with the management of feminizing GAHT.

Hipogonadismo masculino

Male hypogonadism (HG) is defined as the functional incompetence of the gonads with suboptimal or altered production of hormones and germ cells. The prevalence between 30 and 70 years of age is 10% and increases with age. It is classified according to the origin, as primary hypergonadotropic HG, secondary hypothalamic-pituitary hypogonadotropic HG and HG due to peripheral resistance to the androgenic effect. The diagnosis requires clinical suspicion and hormonal determinations that confirm it. The main treatment is the administration of testosterone by transdermal or injectable route, with the option of using GnRH or gonadotropins.

Studies on drug delivery from dissolving microneedle and its uptake in tissue

Abstract In this study, a mathematical model for transdermal drug administration using a dissolving conical microneedle (MN) is developed. The drug is absorbed in the blood compartment after passing through the skin’s viable epidermis. Reversible reaction kinetics then allow the drug to enter the tissue compartment. An unsteady reaction equation is used to predict the drug’s distribution into the skin following MN’s dissolution. An unsteady reaction mechanism is used to determine the concentrations in the blood and tissue compartments. Using the fourth-order Runge–Kutta method, the governing equations with their initial conditions are solved numerically. The MN is expected to dissolve completely in 108.1 s, according to the predicted results, while the concentration in the skin peaks at 94.4 s. The concentrations in the tissue and blood compartments, however, reach their respective maximal amounts later on. In this investigation, the impacts of the drug’s mass fraction, volume fraction, and penetration rate cannot be completely ruled out. A thorough sensitivity analysis has been carried out for some of the parameters involved. Our findings closely align with the findings reported in the literature.

Polymeric Advancements in Transdermal Drug Delivery: A Comprehensive Review on Stability, Safety, and Biocompatibility

AbstractTransdermal drug delivery systems have received a lot of attention due to their noninvasive nature and possible advantages over standard drug administration methods. Because transdermal administration systems skip the gastrointestinal tract and hence avoid hepatic first pass metabolism, also the chance of adverse effects such as liver malfunction and gastrointestinal tract discomfort is low. This comprehensive review explores the various aspects of polymeric advancements in transdermal drug delivery, encompassing their roles as matrix and microreservoir formers, microneedles, pressure sensitive adhesives, rate controlling membranes, and many other components. The article emphasizes the importance of biocompatibility, chemical compatibility, and stability of polymers within the transdermal delivery system. Furthermore, it delves into the recent advancements in synthetic and natural polymer‐based transdermal drug delivery systems. Thus, a comprehensive search strategy is conducted in electronic databases such as PubMed, Scopus, and Web of Science to write this review paper. The scope of this investigation involves an in‐depth study of the various polymeric materials used, their formulations, and the mechanisms that support their efficacy in delivering medications over the skin barrier. Additionally, it explores the challenges associated with stability and safety concerns, while highlighting novel approaches to overcome these problems. Furthermore, the review discusses the biocompatibility of polymeric materials, crucial for ensuring minimal adverse effects and maximum therapeutic efficacy.

Transdermal Carboxytherapy for Treating Vulvovaginal Atrophy: A Pilot Study

Objective: Genitourinary syndrome of menopause (GSM) is a prevalent disorder that can negatively impact the overall health, sexual function, and quality of life of affected women; however, available data do not support specific treatment protocols. A novel product enables the noninvasive transdermal administration of carboxytherapy with a topical gel (CO2Lift®, Lumisque, Inc.; Weston, FL). The following randomized, placebo-controlled pilot study assessed the safety and efficacy of the transdermal carboxytherapy gel for treating GSM-related vulvovaginal changes. Methods: Menopausal or postmenopausal women 40 to 70 years old with signs or symptoms of vulvovaginal atrophy and Female Sexual Dysfunction were randomized to receive topical carboxytherapy gel (n=40) or placebo gel (n=10) in a randomized, double-blind fashion. The assigned treatments were placed into the vagina and on the vulva for 45 minutes before removal. Treatment was applied daily for 5 days, stopped for 2 days, then continued for 5 additional days. Subjects completed four validated pre- and posttreatment questionnaires to assess female sexual function, sexual health, and genital self-image. Additionally, control (n=10) and treatment subjects (n=10) were randomized to undergo 3 mm pre- and posttreatment punch biopsies of vulva and vaginal tissue. Results: Overall, carboxytherapy-treated subjects achieved significant improvements in Female Sexual Function Index scores with strong positive correlations between sexual desire and arousal, arousal and sexual satisfaction, and sexual satisfaction and desire. The Day-to-Day Impact of Vaginal Aging Questionnaire results demonstrated a significant difference in mean pre- and posttreatment values for each assessment among subjects receiving topical carboxytherapy. Biopsy improvements included hyperplasia of the keratinized squamous epithelium, discrete hyperplasia of the basal layer and neovascularization, and increased thickness of mucous squamous epithelium. There were no adverse events. Conclusion: Transdermal carboxytherapy represents a safe, noninvasive means of treating the genitourinary syndrome of menopause symptoms and is suitable for home use. Additional research on this treatment is warranted.

Design Principles and Applications of Ionic Liquids for Transdermal Drug Delivery.

Ionic liquids (ILs) are salts with melting points typically <100°C, composed of specific anions and cations. Recently, IL application has expanded into material engineering and biomedicine. Due to their unique properties, ILs have garnered significant interest in pharmacological research as solubilizers, transdermal absorption enhancers, antibacterial agents, and stabilizers of insoluble pharmaceutical active ingredients. The improvement of skin permeability by ILs is closely associated with their specific physicochemical characteristics, which are identified by their ionic composition. However, the existing literature on transdermal medication administration is insufficient in terms of a comprehensive knowledge base. This review provides a comprehensive assessment of the design principles involved in IL synthesis. Additionally, it discusses the methods utilized to assess skin permeability and provides a focused outline of IL application in transdermal drug administration.

Hispidulin-rich fraction of Clerodendrum fragrans Wild. (Sesewanua) dissolving microneedle as antithrombosis candidate: A proof of concept study

Existing conventional antithrombosis drugs have caused many side effects, opening up opportunities for the development of new thrombotic drugs. There is potential to use the hispidulin-rich fraction of sesewanua (HRFS) as a new antithrombotic. The oral route limitation of hispidulin, as a low water solubility and non-polar compound, can be addressed. This study explores the potential of HRFS in the form of dissolving microneedles (DMN). The formula was created using polymers such as polyvinyl alcohol (PVA), polyvinyl pyrrolidone K-30 (PVP), and non-ionic surfactant. Ex vivo permeation studies found that 184.95 µg/cm2 of hispidulin was released 60 h after the best formulation. After 14 days of applying HRFS-DMN, the anticoagulant and antioxidant activity in male albino rats showed higher Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) values and lower Inter Cellular Adhesion Molecule-1 (ICAM-1) values. No statistically significant differences were found between the effects of two and four HRFS-DMN and the injection of heparin at a dosage of 200 IU per kilogram. However, notable distinctions were observed when comparing HRFS-DMN to negative controls, oral and quercetin as positive controls at anti-ICAM activity. The findings confirmed the feasibility of HRFS-DMN for thrombosis and its effectiveness in delivering Hispidulin (HIS) into the bloodstream. This DMN is non-irritating, safe, and painless, showing promising outcomes in enhancing the efficacy of thrombosis treatment via the transdermal route.

Recent Advancements in Nanopharmaceuticals for Novel Drug Delivery Systems.

Nanoparticles have found applications across diverse sectors, including agriculture, food, cosmetics, chemicals, mechanical engineering, automotive, and oil and gas industries. In the medical field, nanoparticles have garnered considerable attention due to their great surface area, high solubility, rapid dissolution, and enhanced bioavailability. Nanopharmaceuticals are specifically designed to precisely deliver drug substances to targeted tissues and cells, aiming to optimize therapeutic efficacy while minimizing potential adverse effects. Furthermore, nanopharmaceuticals offer advantages, such as expedited therapeutic onset, reduced dosages, minimized variability between fed and fasted states, and enhanced patient compliance. The increasing interest in nanopharmaceuticals research among scientists and industry stakeholders highlights their potential for various medical applications from disease management to cancer treatment. This review examines the distinctive characteristics of ideal nanoparticles for efficient drug delivery, explores the current types of nanoparticles utilized in medicine, and delves into the applications of nanopharmaceuticals, including drug and gene delivery, as well as transdermal drug administration. This review provides insights into the nanopharmaceuticals field, contributing to the development of novel drug delivery systems and enhancing the potential of nanotechnology in healthcare.

A Review: Microneedle Drug Delivery

The various common techniques for transdermal medication delivery include hypodermic needles, topical lotions, and transdermal patches. Because the stratum corneum layer of the skin acts as a barrier for molecules, the action of most therapeutic medicines is restricted, and only a few molecules are able to penetrate and reach the location of action. A novel type of delivery technology known as micro needles aids in improving medication distribution through this channel and addressing the many issues associated with traditional formulations. Because of the problems associated with oral medication delivery methods, transdermal drug administration utilising micro needles is gaining popularity. The possibilities and uses of micro needles are discussed in this review. Micro needles of many sorts can be manufactured, including solid, dissolving, hydrogel, coated, and hollow micro needles. The fabrication process chosen is determined on the kind and material of the micro needle. This technique is now being used in a variety of sectors, including oligonucleotide distribution, vaccine administration, insulin delivery, and even cosmetics.

Formulation and evaluation of herbal microsphere gel

Formulation and evaluation of herbal microsphere gel involves designing a gel-based delivery system for herbal active ingredients encapsulated within microspheres. The process typically includes selecting suitable herbal extracts, encapsulating them into microspheres using techniques like solvent evaporation or emulsion-solvent evaporation, and then incorporating these microspheres into a gel base. Evaluation criteria may include physical characteristics (particle size, morphology), drug release kinetics, rheological properties, stability, and efficacy of the herbal ingredients. This approach aims to enhance the stability, controlled release, and therapeutic efficacy of herbal compounds, offering potential applications in various fields including pharmaceuticals, cosmetics, and personal care products. This present study demonstrated the effectiveness of carbopol based herbal gel containing extracts of tamarind possessing antibacterial activity. Thus, the formulated herbal gel incorporated with tamarind extracts show great promises in the management of antibacterial activity. Gel loaded with microspheres of tamarind was prepared with aim to deliver the drug which passes through transdermal route as it provides quick onset of action when compared to oral route. This gel loaded with microspheres of tamarind was successfully prepared using solvent evaporation method.

Antinociceptive activity of transdermal nanostructured surfactant-based systems containing duloxetine hydrochloride

Duloxetine hydrochloride (DLX) is a serotonin and norepinephrine reuptake inhibitor that is effective in the treatment of chronic pain. However, the drug has several adverse reactions and extensive hepatic first-pass effect. This study aimed at developing surfactant-based formulations such as liquid crystals (LCs) and evaluating the influence of the formulations on DLX skin permeation and in vivo antinociceptive activity. Thereafter, the formulations were obtained using PEG-40 Hydrogenated Castor Oil, Tween 80, licuri oil and water. The systems selected showed isotropy, high viscosity and rheology suggestive of LCs. The systems presented ability to permeate DLX through the skin. ATR-FTIR demonstrated that formulations promoted lipid disorganization and modification of protein conformation, facilitating the drug diffusion through the stratum corneum. Moreover, the formulation loaded with DLX showed high antinociceptive activity in mice (tests of acetic acid-induced abdominal writhing, formalin and tail immersion) via the transdermal route. The antinociceptive activity was close to that of morphine (i.p.). In conclusion, the LC obtained proved to be a promising system for transdermal delivery of DLX and pain management.

Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications-A Comprehensive Review.

Our comprehensive review plunges into the cutting-edge advancements of polymeric microneedle drug delivery systems, underscoring their transformative potential in the realm of transdermal drug administration. Our scrutiny centers on the substrate materials pivotal for microneedle construction and the core properties that dictate their efficacy. We delve into the distinctive interplay between microneedles and dermal layers, underscoring the mechanisms by which this synergy enhances drug absorption and precision targeting. Moreover, we examine the acupoint-target organ-ganglion nexus, an innovative strategy that steers drug concentration to specific targets, offering a paradigm for precision medicine. A thorough analysis of the clinical applications of polymeric microneedle systems is presented, highlighting their adaptability and impact across a spectrum of therapeutic domains. This review also accentuates the systems' promise to bolster patient compliance, attributed to their minimally invasive and painless mode of drug delivery. We present forward-looking strategies aimed at optimizing stimulation sites to amplify therapeutic benefits. The anticipation is set for the introduction of superior biocompatible materials with advanced mechanical properties, customizing microneedles to cater to specialized clinical demands. In parallel, we deliberate on safety strategies aimed at boosting drug loading capacities and solidifying the efficacy of microneedle-based therapeutics. In summation, this review accentuates the pivotal role of polymeric microneedle technology in contemporary healthcare, charting a course for future investigative endeavors and developmental strides within this burgeoning field.

Transdermal drug delivery system recent advancements: A comprehensive review

"The transdermal route offers numerous benefits when compared to traditional drug delivery methods. These advantages encompass high bioavailability, the absence of first-pass hepatic metabolism, maintaining consistent drug plasma levels, and the non-invasive nature of therapy. Additionally, transdermal drug delivery systems [TDDS] provide prolonged therapeutic effects, reduced side effects, enhanced bioavailability, improved patient compliance, and easy termination of drug therapy. TDDS finds applications not only in pharmaceuticals but also in the skincare and cosmetics industries. Studies have shown that the transdermal route causes minimal skin irritation and demonstrates superior performance in various in vivo parameters compared to oral administration. This review article provides a comprehensive overview of TDDS, highlighting its advantages over conventional dosage forms, addressing limitations, discussing the components of transdermal patches, exploring different types of transdermal patches, describing methods of preparation, and outlining the ideal requirements for TDDS. Furthermore, it delves into regulatory considerations, physicochemical methods of evaluation, therapeutic applications, and recent advancements in the field of transdermal drug delivery systems."

Ionic liquid-based Ionogel: A novel strategy to improve dermal delivery and in vivo efficacy of etodolac in rheumatoid arthritis management

The systemic delivery of Etodolac (ETO) often triggers side effects e.g., myocardial problems, bleeding, etc. thus impeding its clinical usage. Also, ETO exhibits unfavourable physicochemical properties, compelling the need for chronic dosing which could aggravate the condition. The transdermal route not only avoids the systemic toxicity but also enables site-specific action. Yet, the efficacy of this route is constrained due to skin barriers. In the present work, a choline geranate ionic liquid based transdermal gel (CAGE Ionogel) was prepared to improve permeation of ETO. The solubility of ETO increased by ∼19,600-fold in CAGE IL than water. TEM revealed the colloidal shape of ETO-CAGE IL. Moreover, ETO-CAGE Ionogel displayed sustained release for up to 48 h. The ex vivo permeation study revealed a higher flux (∼1.3-fold) than ETO gel. Cytotoxicity assay showed reduced IC50 (∼2.17) relative to ETO in RAW 264.7 cells. In vivo studies in CIA-induced model revealed a decrease in clinical signs of RA. X-ray imaging displayed reduced bone erosion and swelling. The toxicity study showcased no changes in biomarker level suggesting the safety of formulation. Skin compatibility study showed low TEWL implying suitability for topical delivery. The findings affirm the efficacy of transdermal ETO therapy in alleviating RA manifestations.

Review on Nanogel as a Novel Platform for Smart Drug Delivery System

One of the most popular applications of nanotechnology in both topical and internal medicine administration to the body is nanogel technology. The materials comprising the nanoparticulate frameworks are less than 100 nm in a single measurement. The goal of this review paper is to provide a concise overview of the most recent developments in the nanogel medicine delivery framework with regard to drug loading and swelling. It categorises according to links (chemical and physical) and responding behaviour. This article is to give a broad overview of nanogels, their innovative use in many contexts, and current synthesis techniques. NGs use drugs for a variety of reasons, including diagnostics, gene targeting, organ targeting, and many more. Different pulmonary, nasal, transdermal, intra-ocular, oral, and parenteral routes can be used to give NGs. The primary goals of this review are to present broad details on NGs, their characteristics, multiple categories, medication targeting strategies, kinds of drug delivery systems, assessment techniques, and cutting-edge uses for NGs in depth. Keywords: Nanogel, DLS, CD, mechanism of drug release, classification, application

Beyond Skin Deep: Phospholipid-Based Nanovesicles as Game-Changers in Transdermal Drug Delivery.

Transdermal administration techniques have gained popularity due to their advantages over oral and parenteral methods. Noninvasive, self-administered delivery devices improve patient compliance and control drug release. Transdermal delivery devices struggle with the skin's barrier function. Molecules over 500 Dalton (Da) and ionized compounds don't permeate through the skin. Drug encapsulation in phospholipid-based vesicular systems is the most effective skin delivery technique. Vesicular carriers include bi-layered liposomes, ultra-deformable liposomes, ethanolic liposomes, transethosomes, and invasomes. These technologies enhance skin drug permeation by increasing formula solubilization, partitioning into the skin, and fluidizing the lipid barrier. Phospholipid-based delivery systems are safe and efficient, making them a promising pharmaceutical and cosmeceutical drug delivery technique. Still, making delivery systems requires knowledge about the physicochemical properties of the drug and carrier, manufacturing and process variables, skin delivery mechanisms, technological advances, constraints, and regulatory requirements. Consequently, this review covers recent research achievements addressing the mentioned concerns.

Flexible surface acoustic wave technology for enhancing transdermal drug delivery.

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000kDa fluorescent molecules have been delivered up to 1.1mm in agarose gel, and the fluorescent molecules from 4 to 2000kDa have been delivered up to 100µm and 25µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.