Transdermal Drug Delivery Research Articles

Effectiveness of transdermal diclofenac patch versus intramuscular diclofenac injection in management of pain among patients with rib fracture in a tertiary care hospital

Most common injuries in trauma are rib fractures which leads to increase rick of mortality and morbidity. In India alone, there is are about 10 million cases per year for incidence of rib fractures more commonly due to vehicle accidents whereas 6% are of global accidents in India, itself. The current modality of treatment is with NSAID’s for relief of pain in rib fractures. A prospective study of 203 patients with rib fractures found a prevalence of chronic pain 22% and disability of 53%. Thereby, adequate pain management is crucial for improving the recovery and quality of life. The preferred route of administration of analgesics is either oral or intramuscular. This study entails in determining the effectiveness of transdermal Diclofenac patch versus intramuscular administration of Diclofenac.

An overview of Transethosomes: Novel nanocarrier for transdermal drug delivery system

The Human skin is made of different layers and the skin will act as a barrier `and it allows the delivery of the drugs through it which is known as TDDS. The delivery of the drug through the epidermis layer of the stratum corneum is difficult as it never allows large particle-sized molecules through it. So there is a need to decrease the particle size and it can be done with new advancements in transdermal delivery by preparing Deformable vesicles which act as a nanocarrier to deliver the drug by changing their shape while transferring from the epidermis to hypodermis. The most advanced Nanocarriers are Ethosomes, Transferosomes, and transethosomes. In this article we will discuss about the transethosomes and their advancement in the TDDS, The transethosomes are prepared by the use of Phospholipids, Ethanol, Edge activators, and penetration enhancers used to make the deformable vesicles. They are prepared by Cold method, hot method, and thin film hydration methods. Their characterization studies include particle size, Shape, PDI, and entrapment efficiency, drug content, and in vitro evaluation studies. The applications of transethosomes are studied.

Innovative transdermal doxorubicin patches prepared using greenly synthesized iron oxide nanoparticles for breast cancer treatment

ABSTRACT An innovative strategy was formulated to overcome the challenges in delivering doxorubicin (DOX) for breast cancer treatment. Transdermal patches were prepared using carbopol 971 (CP) and polyvinyl alcohol (PVA) loaded with starch-coated iron oxide nanoparticles conjugated to DOX (DOX@St-IONPs). The patches’ physicochemical properties, in vitro drug diffusion, alongside the physical properties of DOX@St-IONPs, and their impact on breast cancer cell lines’ viability were examined. The M1 patch, with a 1:1 CP:PVA ratio and DOX@St-IONPs, showed unique properties, indicating effective delivery. It maintained consistent thickness, weight, and 97% DOX loading. Demonstrated flexibility and acceptable surface pH. M1 displayed fivefold increased drug penetration compared to free DOX patches (flux of 14.85 µg/cm2/h and permeability of 0.95 cm/h), with higher cytotoxicity against triple-negative breast cancer. These results propose promising non-invasive DOX delivery through the developed patches.

3D printing redefines microneedle fabrication for transdermal drug delivery.

Microneedles (MNs) have emerged as an innovative, virtually painless technique for intradermal drug delivery. However, the complex and costly fabrication process has limited their widespread accessibility, especially for individuals requiring frequent drug administration. This study introduces a groundbreaking and cost-effective method for producing MNs utilizing fused deposition modeling (FDM) 3D printing technology to enhance transdermal drug delivery. The proposed fabrication process involves the elongation of molten polylactic acid (PLA) filaments to create meticulously designed conoid and neiloid MNs with smooth surfaces. This study underscores the critical role of printing parameters, particularly extrusion length and printing speed, in determining the shape of the MNs. Notably, the conoid-shaped MNs exhibit exceptional skin-penetrating capabilities. In order to evaluate their effectiveness, the MNs were tested on a polydimethylsiloxane (PDMS) skin model for skin penetration. The results highlight the high potential of 3D-printed MNs for transdermal drug administration. This novel approach capitalizes on the benefits of 3D printing technology to fabricate MNs that hold the promise of transforming painless drug administration for a variety of medical applications.

[Artículo traducido] Presencia de partículas metálicas en parches transdérmicos de medicamentos y riesgo de quemaduras

ObjectiveSkin burns are associated with the presence of metallic components in transdermal drug delivery systems during Magnetic Resonance Imaging, cardioversion or defibrillation procedures.The aim of the study was to review the presence of metallic components in marketed products of transdermal drug delivery systems in Spain. MethodFor each presentation, the summary of product characteristics was reviewed. If the information was not provided, manufacturers were contacted. ResultsWe identified 59 marketed products of transdermal drug delivery systems of 12 different active substances.59.3% of patches contained metallic components or their presence could not be ruled out. Information regarding the need to remove the patch was only included in 8 summaries of product characteristics (13.6%).A table was elaborated and included the following aspects: product, active substance, manufacturer, need to remove the patch before the exposure to magnetic or electric fields and references. ConclusionMore than a half of the patches at the time of the study contained metals or their absence could not be confirmed by the manufacturer. However, this information was only included in 13.6% of summaries of product characteristics.

Preferences and feasibility of long-acting technologies for treatment of hepatitis C virus in low- and middle-income countries: A survey of providers and policymakers.

Long-acting technologies (LATs) for hepatitis C virus (HCV) are under development as a strategy to improve linkage to care, treatment adherence and outcomes. We conducted a survey of HCV treatment prescribers and HCV policymakers in low- and middle-income countries (LMICs) regarding acceptability and feasibility of HCV LATs. We included one-time intramuscular injection, subdermal implant and transdermal patch as potential LAT options. We surveyed participants regarding optimal health system and patient characteristics, concerns, potential barriers, overall feasibility and preferences for HCV LAT as compared to daily oral medication. Overall, 122 providers and 50 policymakers from 42 LMICs completed the survey. Among providers, 93% (113/122) expressed willingness to prescribe LAT and 72% (88/120) of providers preferred LAT if provided at comparable efficacy, safety and cost as current oral treatments. Of providers preferring HCV LAT to daily oral medication, 67% (59/88) preferred injection, 24% (21/88) preferred patch and 9% (8/88) preferred implant. Only 20% (24/122) would prescribe LAT if it were more costly than oral treatment. In regression analysis, no provider characteristics were associated with preference for LAT over oral treatment. Policymakers reported high likelihood that LAT would be included in treatment guidelines (42/50; 84%) and national drug formularies (39/50; 78%) if efficacy, safety and cost were similar to oral treatment. HCV LATs could advance progress to HCV elimination in LMICs by diversifying treatment options to improve treatment coverage and outcomes. Provider preferences from LMICs are a critical consideration in the development of HCV LATs to ensure its early and equitable availability in LMICs.

Development and Ex-Vivo Skin Permeation of Sildenafil Citrate Microemulsion System for Transdermal Delivery.

This study aimed to develop a microemulsion (ME)-based skin delivery platform containing sildenafil citrate (SC)-ME and evaluate its in vitro skin permeability. Accurate MEs were prepared using pseudo-ternary phase diagrams and a full factorial design with three variables at two levels. After the design phase, suitable ratios of oil, water, and a mixture of surfactant (S) and cosurfactant (CS) were selected to prepare various SC-ME formulations. These SC-MEs were analyzed for stability, droplet size, in vitro SC release, skin permeability, and viscosity properties. The droplet size of the ME samples ranged from 6.24 to 32.65 nm, with viscosities between 114 to 239 cps. Release profiles indicated that 26 to 60% of SC was released from the different SC-MEs within 24 hours. All ME formulations significantly enhanced the permeability coefficient (P) through rat skin. Specifically, the flux (Jss) in SC-ME7 increased by approximately 117 times (Jss = 0.0235 mg/cm2.h) compared to the control sample (0.0002 mg/cm2.h). The study concluded that the proportions of the water or oil phase and the S/CS mixture in the MEs significantly influenced the physicochemical characteristics and permeation parameters. The selected MEs improved both the permeability coefficient and the rate of permeation through rat skin. The enhanced drug delivery through and into deep skin layers is a key attribute of an ideal dermal ME. These findings suggest that MEs could serve as effective transdermal delivery systems for SC and similar drugs. However, in vivo assays and clinical research are needed to confirm the therapeutic efficacy of MEs.

Development and Characterization of Transdermal Patches Using Novel Thymoquinone-L-Arginine-Based Polyamide Nanocapsules for Potential Use in the Management of Psoriasis

Thymoquinone (TQ) is a phytochemical compound present in Nigella sativa and has potential benefits for treating dermatological conditions such as psoriasis. However, its clinical use is limited due to its restricted bioavailability, caused mainly by its low solubility and permeability. To overcome this, a new transdermal drug delivery system is required. Nanoparticles are known to enhance material solubility and permeability, and hence, this study aimed to synthesize TQ-loaded L-arginine-based polyamide (TQ/Arg PA) nanocapsules incorporated into transdermal patches for prolonged delivery of TQ. To achieve this, Eudragit E polymer, plasticizers, and aloe vera as penetration enhancer were used to develop the transdermal patch. Furthermore, novel TQ/Arg-PA was synthesized via interfacial polymerization, and the resultant nanocapsules (NCs) were incorporated into the matrix transdermal patch. The Arg-PA NCs’ structure was confirmed via NMR and FTIR, and optimal TQ/Arg-PA NCs containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling of TQ/Arg-PA and the transdermal patch revealed the effective development of spherical NCs with an average particle size of 129.23 ± 18.22 nm. Using Franz diffusion cells and synthetic membrane (STRAT M®), the in vitro permeation profile of the prepared patches demonstrated an extended release of TQ over 24 h, with enhanced permeation by 42.64% when aloe vera was employed. In conclusion, the produced formulation has a potential substitute for corticosteroids and other drugs commonly used to treat psoriasis due to its effectiveness, safety, and lack of the side effects typically associated with other drugs.Graphical

Compatibilizing of cotton fabric with hydrophobic drug cover layer for anti-inflammatory performance with the implementation of ibuprofen

This paper presents active analgesic and anti-inflammatory dressings based on cotton woven material with surface functionalization enabling drug implementation. For this purpose, lactide was polymerized on the surface of cotton textiles to achieve better compatibility with hydrophobic drug and polylactide (PLA)-based macromolecules. Subsequently, ibuprofen-loaded PLA and PLA-PEG were implemented through the exhausting method. Such material was tested for cytotoxicity (toward L929 mouse fibroblasts) and anti-inflammatory activity (towards human Hs68 fibroblasts) based on the secretion of pro-inflammatory cytokines IL-1β and TNF-α. The results showed that the drug attachment and its performance are influenced by a combination of mercerization, bleaching and polylactide grafting, and the release of ibuprofen depends on the drug-loaded layer structure. Moreover, we show that cotton woven fabric with ibuprofen-loaded PLA and PLA-PEG cover layers had anti-inflammatory properties. These new dressings may open possibilities for developing prolonged analgesic and anti-inflammatory materials for wound healing or transdermal drug delivery.

A Comprehensive Review of Essential Oil–Nanotechnology Synergy for Advanced Dermocosmetic Delivery

This review investigates the convergence of nanotechnology and essential oils in advanced dermocosmetic delivery. It outlines the pivotal role of inorganic and polymeric nanoparticles, such as titanium dioxide, zinc oxide, and gold nanocarriers, in cosmeceutical applications, facilitating slow release, deeper skin penetration, and increased retention of active compounds. Essential oils, renowned for therapeutic benefits, face translation challenges due to volatility and low water solubility. This review explores the potential use of plant nanovesicles as carriers, emphasizing safety, stability, and scalability, offering a sustainable and cost-effective industrial application. Nanomaterial integration in consumer products, particularly cosmetics, is prevalent, with nanocarriers enhancing the permeation of bioactive compounds into deeper skin layers. The review emphasizes recent nanotechnological advancements, covering nanoparticle penetration, experimental models, and therapeutic applications in dermatology, ranging from non-invasive vaccination to transdermal drug delivery. Additionally, the review delves into nanomaterials’ role in addressing skin aging, focusing on tissue regeneration. Nanomaterials loaded with cosmeceuticals, such as phytochemicals and vitamins, are explored as promising solutions to mitigate signs of aging, including wrinkles and dry skin, providing innovative approaches to skin rejuvenation. Overall, the review offers a comprehensive synthesis of essential oil–nanoparticle synergy, shedding light on the current landscape and future potential of advanced dermocosmetic delivery systems.

Transdermal drug delivery mediated by acoustic vortex beam

Ultrasound-mediated transdermal drug delivery exhibits various advantages such as biocompatibility, controllability and safety, which attracts plenty of interests within biomedical field. Current researches mostly emphasizes the acoustic cavitation generated by planar or focused waves while neglecting other physics that occur during transportation. Our experimental study illustrates the presence of an acoustic vortex (AV) beam that exhibits a lower acoustic intensity and typically means a lower dose of inertial cavitation, yet achieves a more efficient delivery. Such a result calls for the fundamental mechanism of ultrasound-mediated transdermal transfer using the AV beam. In this work, according to our knowledge, the AV beam is firstly introduced to ultrasound-mediated transdermal medication delivery. The transversal acoustic radiation force (T-ARF), which is the primary characteristic carried by the acoustic vortex beam, and its contribution to the transport enhancement are investigated. It is shown that a focused AV (FAV) beam with a maximal acoustic pressure of 200 kPa induces a pN-level T-ARF, which promotes the enlargement of pores on the stratum corneum and thereby enhances the permeability, as compared with a zero-order (non-vortex) counterpart. This contribution of the T-ARF is validated by the experimental transport on the cellulose membrane, which exhibits a significantly increased membrane porosity and delivery efficiency. The favorable results introduce the new degree of freedom into the ultrasound-mediated transdermal drug transport based on AV beam, and thereby promotes the development of a combined control strategy for more precise and efficient transdermal drug delivery in conjunction with the administration of acoustic cavitation.

Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects.

Transdermal nicotine patches (TNPs), administering nicotine into the bloodstream through skin, have been widely used as nicotine replacement therapy, and exposure to nicotine can be detected by measurement of plasma cotinine concentration. In animal studies, nicotine treatment could increase the number of endothelial progenitor cells (EPCs), but the effect of TNPs on circulating EPCs and their activity in humans remained unclear. This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers. In parallel, pulse wave analysis (PWA) was applied to evaluate the vascular effect of TNP treatments. Twenty-one participants (25.8 ± 3.6 years old, 10 males) used TNP (nicotine: 4.2 mg/day) for 7 consecutive days. During the treatment, the CD34+ EPCs progressively increased in number. In addition, the number of EPCs positive for CD34/KDR, CD133, and CD34/CD133 were also increased on day 7 of the treatment. Furthermore, the early EPC colony-forming function and migration activity were increased with the plasma cotinine level positively correlating with change in colony-forming unit number. PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.

Spray: Film Forming System Promising as Transdermal Drug Delivery System

Transdermal drug delivery systems offer numerous advantages over conventional routes, including improved patient compliance and reduced systemic side effects. Spray-on film forming systems (SFFS) have emerged as a novel and versatile approach for delivering drugs through the skin. This abstract presents an overview of SFFS technology, highlighting its potential in transdermal drug delivery. SFFS formulations consist of a solution or suspension of drug molecules and polymers, which upon spraying onto the skin, form a thin, uniform film that adheres to the application site. This film acts as a reservoir for drug release, providing controlled and sustained delivery over time. The versatility of SFFS allows for the incorporation of various drugs, including small molecules, peptides, and proteins, catering to a wide range of therapeutic needs. Moreover, SFFS offers advantages such as ease of application, improved bioavailability, and enhanced skin permeation compared to traditional dosage forms. This abstract summarizes recent advancements in SFFS technology, including formulation strategies, characterization methods, and in vitro/in vivo evaluations. Additionally, challenges such as skin irritation, film integrity, and scalability are discussed, along with potential solutions. Overall, SFFS holds great promise as a transdermal drug delivery system, offering opportunities for enhanced therapeutic outcomes and patient convenience.

The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.

Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model. Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature (p > 0.063). There was no significant effect of treatment on heart rate (p = 0.364). There was a significant effect of time (p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h. Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.

Application of hydrogel microneedles in the oral cavity.

Microneedles are a transdermal drug delivery system in which the needle punctures the epithelium to deliver the drug directly to deep tissues, thus avoiding the influence of the first-pass effect of the gastrointestinal tract and minimizing the likelihood of pain induction. Hydrogel microneedles are microneedles prepared from hydrogels that have good biocompatibility, controllable mechanical properties, and controllable drug release and can be modified to achieve environmental control of drug release in vivo. The large epithelial tissue in the oral cavity is an ideal site for drug delivery via microneedles. Hydrogel microneedles can overcome mucosal hindrances to delivering drugs to deep tissues; this prevents humidity and a highly dynamic environment in the oral cavity from influencing the efficacy of the drugs and enables them to obtain better therapeutic effects. This article analyzes the materials and advantages of common hydrogel microneedles and reviews the application of hydrogel microneedles in the oral cavity.

Recent progress of polymeric microneedle-assisted long-acting transdermal drug delivery.

Microneedle (MN)-assisted drug delivery technology has gained increasing attention over the past two decades. Its advantages of self-management and being minimally invasive could allow this technology to be an alternative to hypodermic needles. MNs can penetrate the stratum corneum and deliver active ingredients to the body through the dermal tissue in a controlled and sustained release. Long-acting polymeric MNs can reduce administration frequency to improve patient compliance and therapeutic outcomes, especially in the management of chronic diseases. In addition, long-acting MNs could avoid gastrointestinal reactions and reduce side effects, which has potential value for clinical application. In this paper, advances in design strategies and applications of long-acting polymeric MNs are reviewed. We also discuss the challenges in scale manufacture and regulations of polymeric MN systems. These two aspects will accelerate the effective clinical translation of MN products.

Recent Advances in Development of Vesicular Carrier for Transdermal Drug Delivery: A Review

Transdermal drug delivery has gained significant attention as a non-invasive and convenient method for administering drugs. However, the stratum corneum, the outermost layer of the skin, poses a significant barrier to drug permeation. To overcome this challenge, vesicular carriers have emerged as promising systems for enhancing drug delivery through the skin. This review highlights recent advances in the development of vesicular carriers for transdermal drug delivery. Liposomes, niosomes, transfersomes, ethosomes, and solid lipid nanoparticles are among the commonly used vesicular carriers. These carriers offer advantages such as improved drug solubility, prolonged drug release, and enhanced drug stability. Additionally, they can encapsulate a wide range of drugs, including hydrophilic and lipophilic compounds. Various strategies have been employed to optimize vesicular carriers for transdermal drug delivery. These include modifying the vesicle composition, size, and surface charge to enhance skin penetration. The incorporation of penetration enhancers, such as surfactants, has also been explored to improve drug permeation across the skin. Furthermore, advancements in nanotechnology have led to the development of novel vesicular carriers, such as nanostructured lipid carriers and elastic liposomes. These carriers offer improved drug loading capacity, sustained release profiles, and enhanced skin penetration. Moreover, the use of vesicular carriers has shown promise in delivering a wide range of therapeutic agents, including small molecules, peptides, proteins, and genetic material. The ability to encapsulate and deliver these diverse drug entities opens new possibilities for transdermal drug delivery in various therapeutic areas.

Design of a Novel Delivery Efficiency Feedback System for Biphasic Dissolving Microarray Patches Based on Poly(Lactic Acid) and Moisture-Indicating Silica.

Dissolving microarray patches (DMAPs) represent an innovative approach to minimally invasive transdermal drug delivery, demonstrating efficacy in delivering both small and large therapeutic molecules. However, concerns raised in end-user surveys have hindered their commercialization efforts. One prevalent issue highlighted in these surveys is the lack of clear indicators for successful patch insertion and removal time. To address this challenge, a color-change-based feedback system is devised, which confirms the insertion and dissolution of DMAPs, aiming to mitigate the aforementioned problems. The approach combines hydrophilic needles containing model drugs (fluorescein sodium and fluorescein isothiocyanate (FITC)-dextran) with a hydrophobic poly(lactic acid) baseplate infused with moisture-sensitive silica gel particles. The successful insertion and subsequent complete dissolution of the needle shaft are indicated by the progressive color change of crystal violet encapsulated in the silica. Notably, distinct color alterations on the baseplate, observed 30 min and 1 h after insertion for FITC-dextran and fluorescein sodium DMAPs respectively, signal the full dissolution of the needles, confirming the complete cargo delivery and enabling timely patch removal. This innovative feedback system offers a practical solution for addressing end-user concerns and may significantly contribute to the successful commercializationof DMAPs by providing a visualized drug delivery method.

Fabrication, evaluation, and enhanced penetration of vinyl and cellulose-engineered transdermal patch of nifedipine using essential oil as penetration enhancer

The aim of this study was to develop and evaluate the transdermal patch formulations of nifedipine. The patch formulations containing nifedipine were prepared and optimized with different ratios of vinyl and cellulose-derived polymers, drug contents, and permeation enhancers. Among the various formulations, the patch formulation containing a 1:5 ratio of ethyl cellulose and polyvinyl pyrrolidone was selected for ex vivo pharmacokinetic study based on in vitro permeation studies using stratum corneum of the pig’s skin. The cumulative percentage release after the transdermal administration of the optimized patch formulation was 71.43%, and the plasma concentration of nifedipine was maintained for 16 hrs. The physicochemical evaluation study including flatness, thickness, moisture content and uptake, drug content in vitro release, and ex vivo permeation indicated satisfactory results. The formulation batch with clove oil as a penetration enhancer has shown better ex vivo permeation as compared to the formulations without enhancers and another synthetic enhancer. These results suggest that the optimized patch formulation Q3 could be further developed for clinical applications, providing the therapeutic plasma level of nifedipine over an extended period. Hence analyzing the results of the evaluation tests, in vitro and ex vivo data on the preparation and optimization of nifedipine-loaded transdermal patch, it can be concluded that the formulation shows its feasibility as an effective transdermal delivery system for nifedipine.

An Overview on Stimuli Sensitive Drug Delivery System

Stimuli-sensitive systems are a state of reactivity to sensory stimulation or excitability. These systems respond to changes in the body’s physiology due to environmental factors such as temperature, enzymes, glucose, magnetic fields, redox reactions, ions, and more. They are particularly useful for the controlled and sustained delivery of drugs in the body. Controlled drug delivery has become a standard criterion in modern pharmaceutical product design, with ongoing intensive research aimed at achieving a superior drug product characterized by effectiveness, reliability, and safety. These stimuli-sensitive systems are employed in various forms for different purposes, including parenteral, ocular, peroral, rectal, vaginal, nasal, dermal, and transdermal drug delivery. This study focuses on the latest advancements in stimuli-sensitive drug delivery systems, aiming to address the limitations of traditional therapeutic methods. The goal is to achieve targeted drug release in specific areas using various endogenous and exogenous stimuli. This allows for personalized and patient-centric treatment strategies. The development of stimuli-sensitive drug delivery systems remains a significant human endeavor for successful drug delivery, given the various shortcomings of existing conventional systems. To overcome these limitations, various stimuli-sensitive drug delivery systems (DDSs) have been developed in recent years