Search

Atopic dermatitis (AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their application is primarily constrained by poor solubility, instability, and limited permeability. The transdermal drug delivery system (TDDS) offers potential solutions for transdermal delivery, enhanced penetration, improved efficacy, and reduced toxicity of natural drugs, aligning with the requirements of modern AD treatment. This review examines the application of hydrogels, microneedles (MNs), liposomes, nanoemulsions, and other TDDS-carrying natural products in AD treatment, with a primary focus on their effects on penetration and accumulation in the skin. The aim is to provide valuable insights into the treatment of AD and other dermatological conditions. [ABSTRACT FROM AUTHOR]

In the recent years, transdermal drug delivery system (TDDS) has gained a lot of success for drug delivery. Transdermal patches have been utilized for delivering the drugs via TDDS. These patches deliver drugs in dissolve lipid form, that enables them to have desired efficiency. Recent advancement in transdermal patches has resulted in formation of novel transdermal patches such as smart patches, degradable, dimensional (3D)-printed patches and release patches, etc. These patches have been utilized in vaccines, gene therapy, insulin delivery, hormonal deficiencies, cardiovascular diseases, etc. This review summarizes the recent advancements in transdermal patches as well as its latest applications. [ABSTRACT FROM AUTHOR]

Recently, drug release applications through the skin have become very popular. One of the most remarkable of these drug release applications is transdermal drug release systems, which are drug release methods that allow the active substance to pass into the systemic circulation through the skin or artificial membranes. In this study, the optimization conditions required for the release and permeation tests of a gel drug containing the active substance thiocolchicoside were comparatively investigated using synthetic membranes without human or animal skin. For this purpose, the permeability of the gel drug in gel form and the active ingredient thiocolchicoside was carried out using Franz Diffusion Cell. As a result of the investigations, it was observed that the best synthetic membrane for the permeability of thiocolchicoside in the Franz Diffusion Cell was the Supor membrane. In addition, the method's relative standard deviation values, detection, and quantification limits were determined, and permeation studies were carried out. In this study, the correlation coefficient was found to be 0.9992, and the limits of detection and quantification were 0.026 and 0.078 µg/L. In this way, the sensitivity and reliability of the validation study were determined.

Aim: This study focuses on developing and evaluating a transferosomal gel containing clotrimazole and miconazole nitrate, antifungal medications used to treat fungal infections, including superficial tinea and nail infections. Materials and Methods: The MI-CTM transferosomes were created using rotary film evaporation and optimized using the Box-Behnken statistical design. They were evaluated for drug concentration, viscosity, Spreadability, pH, and in vitro release kinetics after being embedded in a Carbopol 934 gel. Results: Particle sizes ranging from 145±0.604 nm to 760±0.684 nm and a zeta potential ranging from -2.8 to -41.8, the produced MIC transferosomes exhibited a high EE% ranging from 15.6±0.66%) to (80.25±1.85%). Transferosomes' surface morphology was assessed using a scanning electron microscope, and it was discovered that the vesicles had a spherical form. A 24 hr in vitro release study was conducted for the optimized formulation, showing improved drug release of 86.94% and 89.87% CDR for clotrimazole and miconazole nitrate, respectively. After conducting a kinetic release research, the formulation for miconazole nitrate and the clotrimazole medication followed the non-Fickian transport mechanism described by Peppas and first order kinetics, respectively. There was no noticeable deterioration of the medication based on the stability data, which included no appreciable changes in pH, drug content, or cumulative percentage drug release. Conclusion: Miconazole nitrate and clotrimazole in transferosomal gel, thus, increase medication application frequency while simultaneously enhancing patient compliance. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient's skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs. [ABSTRACT FROM AUTHOR]

Given the extensive first pass metabolism of rizatriptan in oral administration and its delayed absorption during a migraine attack as a result of gastric stasis, focus has been on transdermal delivery. The main purpose of this study is to prepare and assess transdermal formulation of rizatriptan, loaded on hydrogel microneedles delivery system, to avoid first pass metabolism and also improve its percutaneous permeation rate. Rizatriptan hydrogel microneedles were prepared using micromolding method and evaluated in terms of mechanical strength, encapsulation efficiency, permeation and in-vivo skin absorption. Different formulations of rizatriptan microneedles (F1–F5) were successfully prepared using different concentrations of carboxymethyl cellulose and gelatin type A. Rizatriptan hydrogel microneedles demonstrated favorable mechanical properties, including withstanding insertion forces, thereby enhancing its skin insertion ability. In permeation study, the percent cumulative drug released after 24 h ranged between 93.1–100% which means that microneedles were able to deliver the drug effectively. For in-vivo study, F3 formulation was selected due to its superior characteristics over other formulations as it exhibited the highest swelling capacity, and demonstrated favorable mechanical properties. Furthermore, F3 showcased the most controlled drug release over a 24-hour period. Relative bioavailability of F3 microneedles was 179.59% compared to oral administration based on the AUC0-24. The observed AUC0-24 in F3 microneedles was statistically significant and 1.80 times greater than that in oral administration. The higher rizatriptan level in the microneedle demonstrated adequate drug permeability through the rat skin, suggesting the potential of microneedles for enhanced therapeutic effectiveness. [ABSTRACT FROM AUTHOR]

Background: A carrying structure for targeted transdermal drug delivery is a transferosome. These unique liposomes are made of an edge activator and phosphatidylcholine. The most common antiviral drug is acyclovir, a synthetic nucleotide nucleoside analog derived from guanine. It works well to cure the varicella-zoster virus and the virus that causes herpes simplex (HSV), primarily HSV-1 and HSV-2. But its skin permeability is minimal. Therefore, this work aimed to use transferosomes to prepare acyclovir so that it could pass through the skin's barrier function. Objective: This study uses a 32-factorial factorial design to develop a transferosomal gel containing acyclovir through thin-film hydration method for painless acyclovir delivery services for skin disease treatment. Material and Methods: The independent variables are the amount of phospholipid (X1) and tween 80 (X2), while the dependent variables are particle size (Y1) and percentage entrapment efficiency (Y2). To create an ideal formulation, the produced transferosomes were assessed for particle size, in vitro drug release amount, and entrapment efficiency (EE%). A Carbopol 934 gel basis was prepared using the optimized acyclovir transferosome formulation, and its drug concentration, pH, spreadability, viscosity, and stability were assessed. Results: With small particles ranging from 176.6 to 324.4 nm, the produced acyclovir transferosomes had a high EE% range from 66.34 to 76.42 %. According to the in vitro release study, there is a negative correlation between in vitro release and EE%. The formulation TF5, including 1%w/w of carbopol 940, provides a superior profile of drug absorption in vitro. Consequently, acyclovir can enter the skin as transferosomes and cross the stratum corneum barrier. Conclusion: Acyclovir can be transformed into a transfersomal gel, which will improve antiviral efficacy, get over the skin's protective layer, prevent adverse oral reactions, and eventually improve patient adherence. [ABSTRACT FROM AUTHOR]

Abstract The present study proposes an innovative transdermal drug delivery system using ferrocene-incorporated fibers to enhance the bioavailability and therapeutic efficacy of ascorbyl tetraisopalmitate. Using electrospinning technology, the authors created ferrocene polymer fibers capable of highly efficient drug encapsulation and controlled release in response to reactive oxygen species commonly found in wound sites. The approach improves upon previous methods significantly by offering higher drug loading capacities and sustained release, directly targeting diseased cells. The results confirm the potential of ferrocene fibers for localized drug delivery, potentially reducing side effects and increasing patient convenience. The method could facilitate the application of bioactive compounds in medical textiles and targeted therapy.

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others.

The present study proposes an innovative transdermal drug delivery system using ferrocene-incorporated fibers to enhance the bioavailability and therapeutic efficacy of ascorbyl tetraisopalmitate. Using electrospinning technology, the authors created ferrocene polymer fibers capable of highly efficient drug encapsulation and controlled release in response to reactive oxygen species commonly found in wound sites. The approach improves upon previous methods significantly by offering higher drug loading capacities and sustained release, directly targeting diseased cells. The results confirm the potential of ferrocene fibers for localized drug delivery, potentially reducing side effects and increasing patient convenience. The method could facilitate the application of bioactive compounds in medical textiles and targeted therapy. [ABSTRACT FROM AUTHOR]

The transdermal route is an important delivery system for the delivery of both systemic and local effects. The effectiveness of therapy is based on adherence of transdermal dosage form to the skin and physiochemical properties of the drug during therapy. Transdermal Film-Forming Gels when applied to the skin after adherence form a thin film and provide the delivery of drug to the body tissues. Novel 5-Fluorouracil loaded Film-Forming Gels was prepared by utilizing natural polymer (chitosan) with variable concentration of penetration enhancers i.e. oleic acid and tween 80 which further affects the drug release. Prepared Film-Forming Gels were subjected to pH determination, viscosity measurement, homogeneity determination and FTIR analysis. Drying test showed film-forming gel was dried within 15 min after application. Moreover, in-vitro release study confirmed the 83% release over 180 min and the ex-vivo release of FFG9 displayed 81.45% release. This novel system would be an effective dosage form for the delivery of drugs. [ABSTRACT FROM AUTHOR]

Prinsepia utilis seed oil (PUSO) is a natural medication obtained from Prinsepia utilis Rogle seed, which has been used for the treatment of skin diseases. The study aims to prepare ethosomes with high drug loading as a water-soluble transdermal vehicle to enhance the transdermal delivery of PUSO. PUSO-loaded ethosomes (PEs) were prepared using a cold method, and optimized by an orthogonal experimental design with entrapment efficiency (EE) as the dependent variable. The PEs prepared with the optimized formulation showed good stability, with a spherical shape under transmission electron microscopy (TEM), average particle size of 39.12 ± 0.85 nm, PDI of 0.270 ± 0.01, zeta potential of -11.3 ± 0.24 mV, and EE of 95.93 ± 0.43%. PEs significantly increased the skin deposition of PUSO compared to the PUSO suspension (P < 0.001). Moreover, the optimum formula showed significant ameliorative effects on ultraviolet B (UVB) irradiation-associated macroscopic and histopathological changes in mice skin. Therefore, PEs represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation, with the potential for industrialization. [ABSTRACT FROM AUTHOR]

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others. [ABSTRACT FROM AUTHOR]

In past years, various studies have considered transdermal drug delivery system for improving patient compliance. One approach to deliver drug via transdermal route is transdermal patch. These patches include single-layer drug in adhesive patches and micro reservoir transdermal patch & matrix system. Acrylic-acid, hydroxypropyl methylcellulose (HPMC) and polyethylene glycol are commonly used polymers for manufacturing of transdermal patches. Characterization of patches includes patch thickness, weight uniformity, irritation studies, in-vitro drug release and permeation studies. This review summarizes various polymers, types of transdermal patches and evaluation of transdermal patches based on up-to-date data extracted from reputed journals and official websites. [ABSTRACT FROM AUTHOR]

Aim and objectives: A prospective split mouth study was done to compare the efficacy of transdermal ketoprofen versus diclofenac patch after therapeutic orthodontic tooth extraction based on four parameters – pain intensity (VAS), number of rescue analgesia intakes, local allergic reactions and patient tolerability for immediate and 3 consecutive postoperative days. Materials and methods: In total, 33 (66 extraction sites) patients were divided into the ketoprofen patch group and the diclofenac patch group. A single ketoprofen patch (70 cm2 30 mg) was applied following extraction of premolars of the 1st and 4th quadrants and patients were recalled after 1 week for extractions of premolars of the 2nd and 3rd quadrants and diclofenac patch (50 cm2 100 mg) was applied on the deltoid region of the right arm, respectively. Patients were then evaluated under the above‐mentioned parameters. Results: Ketoprofen transdermal patch was found to be more effective in terms of controlling postoperative pain and the minimum number of rescue analgesia tablets taken as compared to diclofenac (statistically significant on 1st and 2nd day) though the former showed the incidence of a local allergic reaction (p‐value 0.002, 0.002 and 0.012), respectively, in few cases which were not seen in case of diclofenac. Conclusion: Overall, both the transdermal patches are effective in terms of safety and providing analgesia, though more research are needed in proving the safeness and efficiency of these transdermal patches with large sample size. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs; as novel solvents for improving the solubility of drugs in carriers; as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs; and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structureactivity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs. [ABSTRACT FROM AUTHOR]

The present study explored the effectiveness of bile-salt-based nano-vesicular carriers (bilosomes) for delivering anti-psychotic medication, Sulpiride (Su), via the skin. A response surface methodology (RSM), using a 33 Box–Behnken design (BBD) in particular, was employed to develop and optimize drug-loaded bilosomal vesicles. The optimized bilosomes were assessed based on their vesicle size, entrapment efficiency (% EE), and the amount of Sulpiride released. The Sulpiride-loaded bilosomal gel was generated by incorporating the optimized Su-BLs into a hydroxypropyl methylcellulose polymer. The obtained gel was examined for its physical properties, ex vivo permeability, and in vivo pharmacokinetic performance. The optimum Su-BLs exhibited a vesicle size of 211.26 ± 10.84 nm, an encapsulation efficiency of 80.08 ± 1.88% and a drug loading capacity of 26.69 ± 0.63%. Furthermore, the use of bilosomal vesicles effectively prolonged the release of Su over a period of twelve hours. In addition, the bilosomal gel loaded with Su exhibited a three-fold increase in the rate at which Su transferred through the skin, in comparison to oral-free Sulpiride. The relative bioavailability of Su-BL gel was almost four times as high as that of the plain Su suspension and approximately two times as high as that of the Su gel. Overall, bilosomes could potentially serve as an effective technique for delivering drugs through the skin, specifically enhancing the anti-psychotic effects of Sulpiride by increasing its ability to penetrate the skin and its systemic bioavailability, with few adverse effects. [ABSTRACT FROM AUTHOR]

Objective: The endeavor is made to criticize the classical indications, preparations and application of Lazūq even after passing many centuries since its inception. Background: According to classical Unani literature, Lazūq is primarily formulated for headache, migraine, toothache, cervical pain, dropping of uvula and different types of pain like sciatica, backache, myalgia and some orthopedic conditions. Its approach is still conventional that encompasses thick sticky stuff of drug/s which is pasted over a cloth or thick paper, consequently, maximum ratio of medicinal properties remains insignificant owed to stratum corneum (layer of skin that functions as a barrier). Devising and method of drug delivery in classical form of Lazūq makes it inconvenient to the patient, thus, it drops patient's compliance and anticipated efficacy. In this day and age, Unani practitioners do not prescribe it very often because of its devising and limited indications documented in classical literature. Hence, it's now becoming out of practice. Whereas, modern medicine is practicing its novel approach epitomized as Transdermal patch for several bodily conditions like Acute post-operative pain, Alzheimer disease, Angina pectoris, Anti-emetic patch, Atrial fibrillation, Attention deficit hyperactivity disorder, Dementia, Depression, Dysmenorrhea, Hypertension, Local dermal analgesia, Menopausal symptoms, Motion sickness, Osteoporosis, Overactive bladder, Parkinson's disease, Post herpetic neuralgia pain, Smoking cessation, Tic disorder, Tourette syndrome and to prevent pregnancy. In transdermal patch, drug is used in micro/nano form with chemically produced permeation enhancers (CPEs) and other smart physio-chemical techniques that makes it very easy to apply, imparts maximum active pharmaceutical ingredients with controlled release of drug. Methodology: Ancient classical Unani formulations of Lazūq was appraised and then its course with respect to today's newer formulations as transdermal patch was reviewed to look for its progress and application in novel dosage form with the advantage of innovations in pharmaceutical and allied sciences. Conclusion: Classical Unani formulations of Lazūq must be reviewed, transformed, evaluated, coped and applied as per the standard operating procedures (SOPs) of transdermal drug delivery system. Future Prospects: New formulations of Lazūq should be designed and appraised from the medicinal treasure of Unani system of medicine for different therapeutic conditions. [ABSTRACT FROM AUTHOR]

Dissolving microneedles (MNs) are novel transdermal drug delivery systems that can be painlessly self-administered. This study investigated the effects of experimental conditions on the mechanical characterization of dissolving MNs for quality evaluation. Micromolding was used to fabricate polyvinyl alcohol (PVA)-based dissolving MN patches with eight different cone-shaped geometries. Axial force mechanical characterization test conditions, in terms of compression speed and the number of compression needles per test, significantly affected the needle fracture force of dissolving MNs. Characterization using selected test conditions clearly showed differences in the needle fracture force of dissolving MNs prepared under various conditions. PVA-based MNs were divided into two groups that showed buckling and unbuckling deformation, which occurred at aspect ratios (needle height/base diameter) of 2.8 and 1.8, respectively. The needle fracture force of PVA-based MNs was negatively correlated with an increase in the needle's aspect ratio. Higher residual water or higher loading of lidocaine hydrochloride significantly decreased the needle fracture force. Therefore, setting appropriate methods and parameters for characterizing the mechanical properties of dissolving MNs should contribute to the development and supply of appropriate products. [ABSTRACT FROM AUTHOR]

The application of pressure-sensitive adhesives (PSAs) in transdermal drug delivery systems (TDDSs) is limited. Insufficient cohesion in TDDS can lead to cold flow, patch displacement, dose inaccuracies, and the ‘dark ring’ phenomenon. To address these issues, we developed a semi-interpenetrating network (semi-IPN) PSA using a 2-hydroxyethylacrylate-modified acrylic copolymer as the linear polymer and poly[tri(propylene glycol) diacrylate] as the cross-linked network. Semi-IPN PSAs have better mechanical properties compared to traditional PSAs. The cohesion of the semi-IPN PSA was 31 times and 1.6 times that of commercially available DURO-TAK®87-2287 and DURO-TAK® 87–4098, respectively, and the cold flow of the semi-IPN PSA was significantly reduced. Furthermore, the semi-IPN PSA adhered to the human forearm for longer time and did not exhibit the ‘dark ring’ phenomenon after removal. When loaded with flurbiprofen, the semi-IPN PSA was found to maintain high levels of drug release and skin permeation amount, and flurbiprofen loading did not affect its superior cohesive performance. In conclusion, the innovative application of the semi-IPN PSA for TDDS showed excellent mechanical properties, effective adhesion to the skin without irritation, and highly effective drug release. These findings indicate that the use of the semi-IPN is both simple and highly effective for TDDS.

Microneedles (MNs) can be used for the topical treatment of skin disorders as they directly deliver therapeutics to the site of skin lesions, resulting in increased therapeutic efficacy while having minimum side effects. MNs are used to deliver different kinds of therapeutics (e.g., small molecules, macromolecules, nanomedicines, living cells, bacteria, and exosomes) for treating various skin disorders, including superficial tumors, wounds, skin infections, inflammatory skin diseases, and abnormal skin appearance. The therapeutic efficacy of MNs can be improved by integrating the advantages of multiple therapeutics to perform combination therapy. Through careful designing, MNs can be further modified with biomimetic structures for the responsive drug release from internal and external stimuli and to enhance the transdermal delivery efficiency for robust therapeutic outcomes. Some studies have proposed the use of drug-free MNs as a promising mechanotherapeutic strategy to promote wound healing, scar removal, and hair regeneration via a mechanical communication pathway. Although MNs have several advantages, the practical application of MNs suffers from problems related to industrial manufacture and clinical evaluation, making it difficult for clinical translation. In this study, we summarized the various applications, emerging challenges, and developmental prospects of MNs in skin disorders to provide information on ways to advance clinical translation.

Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient’s skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs.

Purpose: We fabricated and characterized polyvinyl alcohol (PVA)-based dissolving microneedles (MNs) for transdermal drug delivery of apomorphine hydrochloride (APO), which is used in treating the wearing-off phenomenon observed in Parkinson's disease. Methods: We fabricated MN arrays with 11 × 11 needles of four different lengths (300, 600, 900, and 1200 μm) by micromolding. The APO-loaded dissolving MNs were characterized in terms of their physicochemical and functional properties. We also compared the pharmacokinetic parameters after drug administration using MNs with those after subcutaneous injection by analyzing the blood concentration of APO in rats. Results: PVA-based dissolving MNs longer than 600 μm could effectively puncture the stratum corneum of the rat skin with penetrability of approximately one-third of the needle length. Although APO is known to have chemical stability issues in aqueous solutions, the drug content in APO-loaded MNs was retained at 25°C for 12 weeks. The concentration of APO after the administration of APO-loaded 600-μm MNs that dissolved completely in skin within 60 min was 81%. The absorption of 200-μg APO delivered by MNs showed a Tmax of 20 min, Cmax of 76 ng/mL, and AUC0–120 min of 2,829 ng・min/mL, compared with a Tmax of 5 min, Cmax of 126 ng/mL, and AUC0–120 min of 3,224 ng・min/mL for subcutaneous injection. The bioavailability in terms of AUC0–120 min of APO delivered by MNs was 88%. Conclusion: APO-loaded dissolving MNs can deliver APO via skin into the systemic circulation with rapid absorption and high bioavailability. [ABSTRACT FROM AUTHOR]

Hydrogels have broad application prospects in drug delivery due to their biocompatibility, high water content and three-dimensional structure. However, the regulation of drug release from hydrogels is an important issue in medical applications. At the same time, water also has an important impact on drug release. In this study, a hydrogel with hydrogen bond and ion dipole interaction (PAHDP) was prepared by introducing catechol group into polymer to regulate drug release. Ten model drugs were selected to explore the relationship and mechanism of action among polymer, drug and water. The results showed that PAHDP had excellent adhesion and safety. Drug release test showed that 10 kinds of drugs had different drug release trends, and the release amount was negatively correlated with drug polarizability and LogP. In addition, in vitro transdermal test and pharmacokinetic results showed that the hydrogel based on PAHDP achieved increased or decreased blood drug concentration, and the area under the concentration-time curve (AUC) of >1.5 times showed its potential to regulate drug release. The mechanism study showed that the hydrogen bond and ion dipole interaction between polymer and drug were affected by drug polarizability and LogP, and the distribution of water in different states was changed. Hydrogen bond and ion dipole interactions synergistically control drug release. Therefore, the mussel inspired PAHDP hydrogel has the potential to become a controllable drug delivery system. [Display omitted] [ABSTRACT FROM AUTHOR]

Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel. [ABSTRACT FROM AUTHOR]

Microneedles are of great interest in diverse fields, including cosmetics, drug delivery systems, chromatography, and biological sensing for disease diagnosis. Self-dissolving ultrafine microneedles of pure sodium hyaluronate hydrogels were fabricated using a UV-curing TiO2-SiO2 gas-permeable mold polymerized by sol-gel hydrolysis reactions in nanoimprint lithography processes under refrigeration at 5 °C, where thermal decomposition of microneedle components can be avoided. The moldability, strength, and dissolution behavior of sodium hyaluronate hydrogels with different molecular weights were compared to evaluate the suitability of ultrafine microneedles with a bottom diameter of 40 μm and a height of 80 μm. The appropriate molecular weight range and formulation of pure sodium hyaluronate hydrogels were found to control the dissolution behavior of self-dissolving ultrafine microneedles while maintaining the moldability and strength of the microneedles. This fabrication technology of ultrafine microneedles expands their possibilities as a next-generation technique for bioactive gels for controlling the blood levels of drugs and avoiding pain during administration. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of the death worldwide. However, the conventional cancer therapy still suffers from several limitations, such as systemic side effects, poor efficacy, and patient compliance due to limited accessibility to the tumor site. To address these issues, the localized drug delivery system has emerged as a promising approach. In this study, we developed an iontophoresis-based transdermal drug delivery system (TDDS) controlled by a smartphone application for cancer treatment. Iontophoresis, a low-intensity electric current-based TDDS, enhances drug permeation across the skin to provide potential for localized drug delivery and minimize systemic side effects. The fundamental mechanism of our system was modeled using finite element analysis and its performance was corroborated through the flow-through skin permeation tests using a plastic-based microfluidic chip. The results of in vitro cell experiments and skin deposition tests successfully demonstrated that our smartphone-controlled iontophoresis system significantly enhanced the drug permeation for cancer treatment. Therefore, this hand-held smartphone-based iontophoresis TDDS could be a powerful tool for self-administrated anticancer drug delivery applications. [Display omitted] • We developed the smartphone-based skin permeation plastic iontophoresis device to administer anticancer drugs. • The doxorubicin released from smartphone-based iontophoresis without microneedles was deeply penetrated into tumor sites. • We can rapidly interrupt anticancer drug permeation that reduces the symptoms of side effects at an early stage. [ABSTRACT FROM AUTHOR]

This research presents novel ibuprofen derivatives in the form of alkyl ester salts of L-amino acids with potential analgesic, anti-inflammatory, and antipyretic properties for potential use in transdermal therapeutic systems. New derivatives of (RS)-2-[4-(2-methylpropyl)phenyl]propionic acid were synthesized using hydrochlorides of alkyl esters (ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, and pentyl) of L-glutamine. These were further transformed into alkyl esters of L-amino acid ibuprofenates through neutralization and protonation reactions. Characterization involved spectroscopic methods, including nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Various physicochemical properties were investigated, such as UV–Vis spectroscopy, polarimetric analysis, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, water solubility, octanol/water partition coefficient, and permeability through pig skin using Franz diffusion cells. The research confirmed the ionic structure of the obtained hydrochlorides of alkyl esters of L-amino acids and ibuprofenates of alkyl esters of L-glutamic acid. It revealed significant correlations between ester chain length and thermal stability, crystallinity, phase transition temperatures, lipophilicity, water solubility, skin permeability, and skin accumulation of these compounds. Compared to the parent ibuprofen, the synthesized derivatives exhibited higher water solubility, lower lipophilicity, and enhanced skin permeability. This study introduces promising ibuprofen derivatives with improved physicochemical properties, highlighting their potential for transdermal therapeutic applications. The findings shed light on the structure–activity relationships of these derivatives, offering insights into their enhanced solubility and skin permeation, which could lead to more effective topical treatments for pain and inflammation. [ABSTRACT FROM AUTHOR]

Skin photodamage, which is induced by ultraviolet (UV) radiation, is a prevalent cause of skin damage. In this study, a transdermal drug delivery system is developed for the topical treatment of skin photodamage, which is composed of tetrahedral framework nucleic acids (tFNAs) and lipoic acid (LA). The tFNAs‐LA (TLA) nanocomposite exhibits excellent biocompatibility, as well as antioxidant, anti‐apoptotic, and anti‐inflammatory capabilities. tFNA, as a carrier, facilitates TLA for cell entry and skin penetration, while the loaded LA enhances the antioxidant and anti‐inflammatory capabilities. In photodamaged human dermal fibroblast (HDF), TLA promotes proliferation and migration while inhibiting apoptosis activation and reactive oxygen species production. Moreover, TLA modulates apoptosis‐related proteins and NF‐κB signaling pathways, increasing cellular secretion while suppressing inflammatory responses in photodamaged HDF cells. In the in vivo experiment, topical application of TLA promotes tissue healing in photodamaged skin, and regulates the expression of inflammation and collagen‐related proteins. It is suggested that the transdermal ability of TLA enables non‐invasive therapy for skin photodamage, highlighting the potential of employing nucleic acid‐based transdermal drug delivery systems for skin disease. [ABSTRACT FROM AUTHOR]

Skin diseases are among the most prevalent non-fatal conditions worldwide. The transdermal drug delivery system (TDDS) has emerged as a promising approach for treating skin diseases, owing to its numerous advantages such as high bioavailability, low systemic toxicity, and improved patient compliance. However, the effectiveness of the TDDS is hindered by several factors, including the barrier properties of the stratum corneum, the nature of the drug and carrier, and delivery conditions. In this paper, we provide an overview of the development of the TDDS from first-generation to fourth-generation systems, highlighting the characteristics of each carrier in terms of mechanism composition, penetration method, mechanism of action, and recent preclinical studies. We further investigated the significant challenges encountered in the development of the TDDS and the crucial significance of clinical trials. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that can lead to synovitis, cartilage destruction, and even joint damage. Dexamethasone (DEX) is a commonly used agent for RA therapy on inflammation manage. However, the traditional administering DEX is hampered by low efficiency and obvious adverse effects. Therefore, in order to efficiently deliver DEX to RA inflamed joints and overcome existing deficiencies, we developed transdermal formation dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel), validated their transdermal efficiency, evaluated its ability to target activated macrophages, and its anti-inflammatory effect. The DS-FLs/DEX exhibited excellent biocompatibility, sustainable drug release, and high uptake by lipopolysaccharide (LPS)-activated macrophages. Furthermore, the DS-FLs/DEX hydrogel showed desired skin permeation as compared with regular liposome hydrogel (DS-RLs/DEX hydrogel) due to its good deformability. In vivo, when used the AIA rats as RA model, the DS-FLs/DEX hydrogel can effectively penetrate and accumulate in inflamed joints, significantly improve joint swelling in RA rats, and reduce the destructive effect of RA on bone. Importantly, the expression of inflammatory cytokines in joints was inhibited and the system toxicity did not activate under DS-FLs/DEX hydrogel treatment. Overall, these data revealed that the dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel) can prove to be an excellent drug delivery vehicle against RA.

This study aimed to screen, design, and evaluate an optimal nanoemulsion formulation for Aucklandiae Radix extraction (ARE). A simple lattice design (SLD) method was used to determine the preparation process of Aucklandiae Radix extract-nanoemulsions (ARE-NEs). After optimization, the average particle size of ARE-NEs was 14.1 ± 1.1 nm, polydispersity index was 0.2376, and pH was 6.92. In vitro penetration tests verified that the permeability ratios of costunolide (CE), dehydrocostus lactone (DE), and ARE-NEs were approximately 6.33 times and 8.20 times higher, respectively, than those of the control group. The results of the pharmacokinetic study indicated that after topical administration, the content of the index components of ARE-NEs increased in vivo, with a longer release time and higher bioavailability in vivo than in vitro. The index components were CE and DE, respectively. In addition, a skin irritation test was conducted on normal and skin-damaged rabbits, aided by HE staining and scanning electron microscopy, to reveal the transdermal mechanism of ARE-NEs and proved that NEs are safe for topical application. ARE-NEs energetically developed the properties of skin and penetration through the transdermal route, which were secure when applied via the transdermal delivery system. [ABSTRACT FROM AUTHOR]

The present study explored the effectiveness of bile-salt-based nano-vesicular carriers (bilosomes) for delivering anti-psychotic medication, Sulpiride (Su), via the skin. A response surface methodology (RSM), using a 33 Box–Behnken design (BBD) in particular, was employed to develop and optimize drug-loaded bilosomal vesicles. The optimized bilosomes were assessed based on their vesicle size, entrapment efficiency (% EE), and the amount of Sulpiride released. The Sulpiride-loaded bilosomal gel was generated by incorporating the optimized Su-BLs into a hydroxypropyl methylcellulose polymer. The obtained gel was examined for its physical properties, ex vivo permeability, and in vivo pharmacokinetic performance. The optimum Su-BLs exhibited a vesicle size of 211.26 ± 10.84 nm, an encapsulation efficiency of 80.08 ± 1.88% and a drug loading capacity of 26.69 ± 0.63%. Furthermore, the use of bilosomal vesicles effectively prolonged the release of Su over a period of twelve hours. In addition, the bilosomal gel loaded with Su exhibited a three-fold increase in the rate at which Su transferred through the skin, in comparison to oral-free Sulpiride. The relative bioavailability of Su-BL gel was almost four times as high as that of the plain Su suspension and approximately two times as high as that of the Su gel. Overall, bilosomes could potentially serve as an effective technique for delivering drugs through the skin, specifically enhancing the anti-psychotic effects of Sulpiride by increasing its ability to penetrate the skin and its systemic bioavailability, with few adverse effects.

BackgroundTransdermal drug delivery systems (TDDS) pose special risks considering a large amount of drug they contain and their modified release properties. We sought to characterize TDDS exposures reported to the National Poison Data System (NPDS).MethodsNPDS was searched for all human exposures to a TDDS from 1/1/2006 to 12/31/2015. Only single-substance TDDS exposures followed to a known medical outcome were included for final analysis. Specific data analyzed was date, sex, age, TDDS product, exposure reason, route of exposure, medical outcome, management site, level of health care facility care, clinical effects, and interventions.ResultsOver that 10-year period, 6746  adults and 1917 pediatric exposures were identified. Exposures declined over the study period. The most common exposure reason in adults was intentional abuse (n = 1622) compared to unintentional-general (n =1 070) in pediatric cases. TDDS ingestion was reported in 4519 adults and 2825 pediatric cases. Fentanyl was the most common substance encountered in adult (n = 4656) and pediatric cases (n = 474). No or minor effect were the most common medical outcomes in both groups. In fentanyl cases, moderate or major outcomes were seen in 54 % (n = 1062) of adult and 26 % (n = 54) of pediatric cases. Naloxone was given in 1080 cases. Ninety-seven deaths (91 adults, 6 pediatrics) were reported, all involving ingestion of the TDDS. Fentanyl was associated with 80 adult and 5 pediatric deaths.ConclusionOverall, single-substance TDDS exposures decreased over the duration of this study and typically resulted in no or mild effects. However, exposures involving fentanyl resulted in higher rates of major or moderate medical outcomes and were associated with multiple deaths.

Ethosomes are novel ethanolic phospholipid vesicles which are significantly used for the transdermal drug delivery. Ethanol is an efficient permeation enhancer which is used in ethosomes about 20-45%. These are non-invasive in nature and have emerged as an area of active research interest because they significantly lead to enhanced skin penetration, improvement in drug delivery, increased drug entrapment efficiency it can deliver both hydrophilic and lipophilic drugs efficiently. Increased patient compliance etc. The drug penetrates the skin surface and gets absorbed by two phases i.e., the ethanol effect and ethosomes effect. Ethosomes are predominantly being used over liposomes because of their greater penetration rate which is attributed to the high concentration of ethanol. Hence it is an active area of research. The primary aim of the review is to provide a comprehensive account on the methods of preparation, properties, characterization, advantages and applications of ethosomes in the management of several skin diseases.

In recent years, nanotechnology has a new era of drug delivery for many drug systems. Transdermal drug delivery is one of the few systems that have recently become a major focal point of research. When compared to traditional drug delivery systems, the Transdermal Drug Delivery System (TDDS) has various advantages. Due to the barrier properties of the Stratum Corneum, TDDS has had limited market success. The introduction of ethosomes, which are soft, malleable vesicular carriers containing ethanol and are tailored for enhanced delivery of active agents, has opened up a new area of vesicular research for transdermal drug delivery. According to various reports, ethosomes have a promising future in improving the efficacy of transdermal delivery of various agents. Ethosomes are also useful for the non-invasive delivery of small, medium and large drug molecules. Ethosome preparation is simple, requires no complicated equipment, and can thus be scaled up to industrial levels. The review emphasises introduction to ethosomes, their composition and preparation methods, evaluation, and their efficiency in penetrating the skin and the use of ethosomes in transdermal medication delivery as being more effective than liposomes or hydroalcoholic solution in terms of quantity and depth. [ABSTRACT FROM AUTHOR]

Besides delivering drug to the body, a drug delivery system aims to improve patient compliance, patient acceptance. The dosage formsavailable for the delivery of topical agents include ointment, paste, CREAM, moisturizing cream and powder. However, cream is more preferabledue to their properties. Present research work is attempted to develop gel by using rice bran wax. Rice bran wax is the vegetable waxextracted from rice bran oil. The oil generally contains 2-6% wax. However it is assumed that on an average it contains 3% wax. Physicochemical tests such as globule size, evaluation of the intrinsic viscosity and homogeneity of cream products, have been traditionallyused to provide reasonable evidence of consistent product performance. However, for the purposes of these studies, the final cream productswere characterized for their clarity, pH, viscosity, spread ability, skin irritation test and in vitro diffusion studies using standard procedure. All the results match with official specifications. [ABSTRACT FROM AUTHOR]

Because of the requirement of long-term treatment for pigmented dermatoses, long-term oral medications can cause many adverse reactions, while topical medications are not effective due to poor skin permeability. The microneedle transdermal drug delivery system can penetrate the stratum corneum and form multiple reversible microchannels, which can significantly improve the permeability of therapeutic drugs and has the advantages of good local targeting, controlled and continuous drug delivery, while avoiding gastrointestinal irritation and liver first-pass effect, etc. It has been tried in the clinical treatment of pigmented disorders such as melasma, vitiligo and dark circles. This paper reviews the mechanisms of the microneedle transdermal drug delivery system, its basic research and clinical application in pigmented skin diseases such as melasma, vitiligo and dark circles under the eyes, in order to provide rationale for clinical application.

Microneedles are of great interest in diverse fields, including cosmetics, drug delivery systems, chromatography, and biological sensing for disease diagnosis. Self-dissolving ultrafine microneedles of pure sodium hyaluronate hydrogels were fabricated using a UV-curing TiO2-SiO2 gas-permeable mold polymerized by sol-gel hydrolysis reactions in nanoimprint lithography processes under refrigeration at 5 °C, where thermal decomposition of microneedle components can be avoided. The moldability, strength, and dissolution behavior of sodium hyaluronate hydrogels with different molecular weights were compared to evaluate the suitability of ultrafine microneedles with a bottom diameter of 40 μm and a height of 80 μm. The appropriate molecular weight range and formulation of pure sodium hyaluronate hydrogels were found to control the dissolution behavior of self-dissolving ultrafine microneedles while maintaining the moldability and strength of the microneedles. This fabrication technology of ultrafine microneedles expands their possibilities as a next-generation technique for bioactive gels for controlling the blood levels of drugs and avoiding pain during administration.

Dissolving microneedles (MNs) are novel transdermal drug delivery systems that can be painlessly self-administered. This study investigated the effects of experimental conditions on the mechanical characterization of dissolving MNs for quality evaluation. Micromolding was used to fabricate polyvinyl alcohol (PVA)-based dissolving MN patches with eight different cone-shaped geometries. Axial force mechanical characterization test conditions, in terms of compression speed and the number of compression needles per test, significantly affected the needle fracture force of dissolving MNs. Characterization using selected test conditions clearly showed differences in the needle fracture force of dissolving MNs prepared under various conditions. PVA-based MNs were divided into two groups that showed buckling and unbuckling deformation, which occurred at aspect ratios (needle height/base diameter) of 2.8 and 1.8, respectively. The needle fracture force of PVA-based MNs was negatively correlated with an increase in the needle’s aspect ratio. Higher residual water or higher loading of lidocaine hydrochloride significantly decreased the needle fracture force. Therefore, setting appropriate methods and parameters for characterizing the mechanical properties of dissolving MNs should contribute to the development and supply of appropriate products.

This research presents novel ibuprofen derivatives in the form of alkyl ester salts of L-amino acids with potential analgesic, anti-inflammatory, and antipyretic properties for potential use in transdermal therapeutic systems. New derivatives of (RS)-2-[4-(2-methylpropyl)phenyl]propionic acid were synthesized using hydrochlorides of alkyl esters (ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, and pentyl) of L-glutamine. These were further transformed into alkyl esters of L-amino acid ibuprofenates through neutralization and protonation reactions. Characterization involved spectroscopic methods, including nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Various physicochemical properties were investigated, such as UV–Vis spectroscopy, polarimetric analysis, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, water solubility, octanol/water partition coefficient, and permeability through pig skin using Franz diffusion cells. The research confirmed the ionic structure of the obtained hydrochlorides of alkyl esters of L-amino acids and ibuprofenates of alkyl esters of L-glutamic acid. It revealed significant correlations between ester chain length and thermal stability, crystallinity, phase transition temperatures, lipophilicity, water solubility, skin permeability, and skin accumulation of these compounds. Compared to the parent ibuprofen, the synthesized derivatives exhibited higher water solubility, lower lipophilicity, and enhanced skin permeability. This study introduces promising ibuprofen derivatives with improved physicochemical properties, highlighting their potential for transdermal therapeutic applications. The findings shed light on the structure–activity relationships of these derivatives, offering insights into their enhanced solubility and skin permeation, which could lead to more effective topical treatments for pain and inflammation.

Exosomes act as emerging transdermal drug delivery vehicles with high deformability and excellent permeability, which can be used to deliver various small-molecule drugs and macromolecular drugs and increase the transdermal and dermal retention of drugs, improving the local efficacy and drug delivery compliance. At present, there are many studies on the use of plant exosome-like nanoparticles (PELNVs) as drug carriers. In this review, the source, extraction, isolation, and chemical composition of plant exosomes are reviewed, and the research progress on PELNVs as drug delivery systems in transdermal drug delivery systems in recent years has elucidated the broad application prospect of PELNVs. [ABSTRACT FROM AUTHOR]

Long-acting transdermal drug delivery system (TDDS) requires high drug-loading and drug controlled-release. To simultaneously improve drug-polymer miscibility and realize drug controlled-release, this work aimed to develop a new pressure sensitive adhesive modified with hydroxyphenyl (HP-PSA) by introducing doubly ionic H-bond into drug-PSA interaction. Eight model drugs divided into R 3 N, R 2 NH and no N type were chosen to understand the characteristics of the HP-PSA and inner mechanism. The results showed that the doubly ionic H-bond between R 3 N and R 2 NH type drugs and HP-PSA, differing from the ionic bond and neutral H-bond, was a reversible and relatively strong interaction. It could significantly enhance their drug-loading by 1.5 to 7 times and control drug release rate to its 1/5 to 1/2 without altering its total release properties, outperforming the commercial Duro-Tak® 87–2510 and Duro-Tak® 87–2852 adhesives. According to the pharmacokinetics results, the high drug-loading patches based on HP-PSA achieved a sustainable plasma drug concentration avoiding burst release, and over 2 times area under concentration-time curve (AUC) as well as 6 times mean residence time (MRT) revealed its potential to realize long-acting drug delivery. Additionally, its safety and mechanical features were satisfied. The mechanism study showed that the repulsion of the ionic drugs in HP-PSA increased drug-loading, and the relatively strong interaction could also control drug release. The incomplete H-bond transfer determined its reversibility, thus making the drug release percentage up to that of non-functional PSA. In conclusion, the high drug-loading efficiency and drug controlled-release capacity of HP-PSA, as well as its unique interaction, would contribute to the development of TDDS. Moreover, the construction of the doubly ionic H-bond would provide further inspiration for various drug delivery systems in the non-polar environment. [Display omitted] [ABSTRACT FROM AUTHOR]