Open research questions in Advancements in Transdermal Drug Delivery

What the literature leaves open

• The ACE–TRIS multicomponent crystal therapeutic potential of ACE, although further pharmacokinetic studies are warranted to confirm these significantly improved the physicochemical findings.

  Enhancement of Solubility, Dissolution, and Anti-Inflammatory Activity of Aceclofenac via Multicomponent Crystal Formation with Tromethamine · 2026 · DOI

• Future research in transdermal drug delivery is expected to focus on advanced technologies such as microneedles, nanocarriers, ethosomes, transferosomes, iontophoresis, and smart transdermal systems to enhance drug permeation and therapeutic efficacy. The integration of nanotechnology and novel polymeric materials may further improve drug loading, controlled release, and skin penetration. In the case of Telmisartan, advanced transdermal delivery approaches may overcome limitations associated with conventional oral therapy and provide improved patient compliance and sustained antihypertensive effects. Furthermore, the application of Quality by Design (QbD) and statistical optimization tools is anticipated to facilitate the development of robust and reproducible transdermal formulations for clinical use.[12,13] 10. CONCLUSION Transdermal drug delivery systems represent a promising alternative to conventional dosage forms for achieving sustained and controlled drug release. Telmisartan possesses suitable physicochemical and pharmacological characteristics that support its incorporation into transdermal formulations. The selection of appropriate polymers, plasticizers, and permeation www.wjpps.com │ Vol 15, Issue 7, 2026. │ ISO 9001: 2015 Certified Journal │ 257 Gauravi et al. World Journal of Pharmacy and Pharmaceutical Sciences enhancers plays a crucial role in determining patch performance. Factorial design serves as an effective optimization tool by systematically evaluating formulation variables and their interactions, thereby reducing experimental workload and improving formulation efficiency. Recent advancements in transdermal technologies have further expanded the potential of Telmisartan delivery systems, suggesting that optimized transdermal patches may provide therapeutic outcomes and patient compliance improved hypertension.[1,2] in the management of REFERENCES 1. Jeong WY, Kwon M, Choi HE, et al. Recent Advances in Transdermal Drug Delivery Systems: A Review. Biomaterials Research. 2021. 2. Crasta A, Painginkar T, et al. Transdermal Drug Delivery System: A Comprehensive Review, 2025. 3. Teaima M, Abdelmonem R, Adel YA, et al. Transdermal Delivery of Telmisartan. Drug Design, Development and Therapy, 2021. 4. Wienen W, Entzeroth M, van Meel JCA, Stangier J, Busch U, Ebner T, et al. A Review on Telmisartan: A Novel, Long-Acting Angiotensin II-Receptor Antagonist. Cardiovascular Drug Reviews, 2000; 18(2): 127–154. 5. Bakheit AHH, Al-Hadiya BMH, Abd-Elgalil AA. Telmisartan. Profiles of Drug Substances, Excipients and Related Methodology, 2015; 40: 371–429. 6. Bird D. Transdermal drug delivery and patches—An overview. Medical Devices & Sensors, 2020; 3(2): e10069. doi: 10.1002/mds3.10069. 7. Bolton S, Bon C. Pharmaceutical Statistics: Practical and Clinical Applications. 5th ed. New York: Marcel Dekker, 2004. 8. Yadav PK, Mishra S. Transdermal Patch of an Antihypertensive Drug: Its Development and Evaluation. World Journal of Pharmaceutical Research, 2017; 6(4): 1354–1371. 9. Review on transdermal patches: optimization in drug administration. Pharmaceutical Sciences Review. 2025. Available from: PMC13193725. 10. Kulkarni RV, Mutalik S, Hiremath D. Formulation and characterization of transdermal patches for controlled delivery of duloxetine hydrochloride. Journal of Analytical Science and Technology, 2016; 7: 1-12. 11. Wang Y, Zeng L, Song W, Liu J. Influencing Factors and Drug Application of Iontophoresis in Transdermal Drug Delivery: An Overview of Recent Progress. Drug www.wjpps.com │ Vol 15, Issue 7, 2026. │ ISO 9001: 2015 Certified Journal │ 258 Gauravi et al. World Journal of Pharmacy and Pharmaceutical Sciences Delivery and Translational Research, 2022; 12(1): 15-26. doi:10.1007/s13346-021- 00898-6. 12. Alkilani AZ, Nasereddin J, Hamed R, Nimrawi S, Hussein G, Abo-Zour H, Donnelly RF.

  DESIGN AND OPTIMIZATION OF TRANSDERMAL PATCHES OF TELMISARTAN USING FACTORIAL DESIGN FOR SUSTAINED DRUG RELEASE: A REVIEW · 2026 · DOI

• Liposomal and gel-based formulations represent two of the most innovative and effective drug delivery systems in dermatology, offering significant advantages over conventional topical treatments. Their ability to enhance drug stability, control release profiles, and improve skin penetration makes them valuable tools for treating a wide conditions. Liposomal range formulations stand out due to their biocompatibility and structural similarity to biological membranes, allowing them to encapsulate both hydrophilic and lipophilic drugs while facilitating deeper skin penetration.

  FORMULATION AND EVALUATION OF LIPOSOMAL GEL CONTAINING CLITORIA TERNATEA EXTRACT FOR TOPICAL DRUG DELIVERY SYSTEM · 2026 · DOI

• Despite the well-documented antimicrobial and antioxidant properties of Parameria laevigata (kayu rapet) bark, its incorporation into a dissolving microneedle (DMN) platform for transdermal acne therapy has not been previously investigated.

  PVA/PVP Dissolving Microneedle Arrays Loaded with Parameria laevigata Extract: Formulation and Characterization for Transdermal Anti-Acne Therapy · 2026 · DOI

• Furthermore, this article analyzes current bottlenecks of this technology, including limited drug loading capacity, insufficient mechanical strength, lack of standardized evaluation systems, and inadequate evidence for clinical translation, aiming to provide theoretical references and technical insights for structural optimization, process improvement, industrialization, and clinical translational application of dissolving microneedle formulations containing TCM active components.

  New Strategies for Transdermal Delivery of Active Components from Traditional Chinese Medicine: Research Progress and Prospects of Dissolving Microneedle Technology · 2026 · DOI

• low viscosity of nanoemulsions and improves formulation stability for topical application [21]. after [22]. application Conventional topical formulations such as ointments and creams often suffer from poor patient acceptability due to greasiness, stickiness, staining, and difficulty in removal contrast, nanoemulgels exhibit superior physicochemical and cosmetic properties including better spreadability, thixotropic behavior, non-greasy nature, ease of application, and improved aesthetic appearance [23].

  Formulation and Evaluation of Herbal Nanoemulgel for Antiinflammatory Activity · 2026 · DOI

• healthcare customized The future of integrated transdermal therapeutic systems requires creation of intelligent, adaptable, and platforms. Enhancement of patient comfort, scalability and device performance can be expected from such systems by developments in biomaterials, additive manufacturing, and nanotechnology. electronics flexible drug Artificial Intelligence (AI) and Machine Learning (ML) have the potential to revolutionize future integrated systems. AI-assisted systems can enable predictive current dosing, modulation, real-time physiological monitoring and closed-loop therapeutic control based on patient-specific responses. ML algorithms can evaluate physiological signs and optimize drug delivery, paving way to customized treatment plans. adaptive In the future, wearable theranostic systems may combine biosensors, wireless communication modules, cloud computing and AI-driven analytics printing to provide remote healthcare management and precision medicine, resulting in smart systems treatment with autonomous diagnosis and 3D capabilities. additive and technologies are capable of manufacturing streamlining the rapid prototyping and customized manufacture of transdermal devices with unique geometries. Further, sustainability and long-term usability can be improved by use of self-powered systems and biodegradable materials.

  Integrated Transdermal Therapeutic Systems: Technologies, Applications and Challenges · 2026 · DOI

• • Preparation methods can be complex and expensive. • Drug loading efficiency may be variable. • Possible burst release of entrapped drug may occur. • Polymer toxicity or incompatibility may affect formulation stability. • Scale-up and industrial manufacturing can be difficult. • Drug leakage during preparation and storage may occur (26). Overall, polymeric microspheres have emerged as highly effective drug carrier systems due to their controlled release properties and ability to improve therapeutic outcomes. Despite certain limitations, continuous advancements in polymer science and formulation technologies are expanding their applications in topical and controlled drug delivery systems (27).

  Polymeric Microsphere-Based Systems for Controlled Topical Drug Delivery: A Comprehensive Review · 2026 · DOI

• Herbal face wash has a bright future because people are becoming more aware about skin health www.wjpps.com │ Vol 15, Issue 6, 2026. │ ISO 9001:2015 Certified Journal │ 1423 Doshi et al. World Journal of Pharmacy and Pharmaceutical Sciences 2. In future, the demand for herbal cosmetics is expected to increase due to growing interest in organic and Ayurvedic product 3. Herbal face wash can also be developed for different skin types such as oily, dry, sensitive, and acne-prone skin. 4. herbal face wash has good commercial value and great potential in the cosmetic and pharmaceutical industries. 5. Advanced packaging and preservation techniques may also increase product shelf life. 6. consumers prefer natural and herbal products because they are safer, gentle on the skin, and eco-friendly. REFERENCE 1 Khan, A.D.*1, and Alam, M.N.1 cosmetic and their associated adverse effects. 2 Malik, Vijay., the drug and cosmetics act, 1940, 18th edition, new Delhi: eastern book company pp 5-6. 3 Darel’s, Z.D., Cosmetics: the medicine of beauty journal of cosmetic dermatology, 2015; 14(2): 91. 4 Schneider, G., Gohla, S., Schreiber, Kaden, W., Schmock, U., Lewer Kuhne, H.S., Kuschel, A., petites, X., Pape, W., Ippon, H., Diem beak, W., in skin cosmetics, Ullmann’s encyclopedia of industrial chemistry 6th vol. Germany: Wiley VCH, 2001; 10: 24-29. 5 Lal, B.B., the Saraswati flows on the continuity of Indian culture., 2002; 56-57. 6 Kanitakis, J., anatomy histology and immunohistochemistry of normal human skin, European Journal of dermatology., 2002; 12(4): 390-401 7 Brown, S.K., Shalita, A., Acne vulgarism, lancet, 1998; 351(9119): 1871 – 1876. 8 Kapoor, V. P., herbal cosmetics for skin and hair care, national botanical research institute., 2005; 4(4): 306-313. 9 Ashish, Baldi., herbal cosmetics: used for skin and hair invent rapid journals, 2012; (1): 1-7. 10 Harsharan, pal, Singh, et al. anti-acne synergistic herbal face wash gel. World journal of pharmaceutical research vol.4, Issue (IX), (2015). 11 Nitin Yadav et al. formulation and development of face wash journal of emerging technologies and innovative research vol. 6, Issue (VI), (2021). 12 Martha Srinivas, et al. current review on herbal face care. international journal of pharmaceutical sciences review and research article no., 17: (2021). www.wjpps.com │ Vol 15, Issue 6, 2026. │ ISO 9001:2015 Certified Journal │ 1424 Doshi et al. World Journal of Pharmacy and Pharmaceutical Sciences 13 Saud agar R.B., Sisodia M.H. Review on herbal cosmetics; 7(7): 573-591. 14 Divya P, Puthusseri B, Neelwarne B, Carotenoid content, its stability during the drying and antioxidant activity of commercial coriander varities. Food Research International, 2012; 45(1): 342-50. 15 Vasoya Dhruval, Vasava Nehali, Vazara Ronak, Vaishali Sharma, Dhananjay Meshram, Formulation Evaluation and stability study of facewash containing polyherbal extract. Research, (2021); 10(9). 16 Yadav Shivkumar, Yadav Puyush, Yadav Deepa Kumar, Maurya Manish Kumar, Muhammed Nadeem, Fakir Muhammad Anjum, Muhammad Issa Kha, Sameena Tehsin, Nutritional and medicinal aspects of coriander. British Food Journal, (2013); 115(5): 743-755. 17 Jangra Satya shree, V.K. Kadam, Sigh Isha, Dushyant, Comparative analysis of Phytochemical profile and antioxidant activity of coriander (Coriandrum Sativum L). Asian Journal of Chemistry (2018).

  FORMULATION AND EVALUATION OF HERBAL FACE WASH · 2026 · DOI

• study effectively imiquimod, while demonstrated an ability to enhance drug retention within the targeted skin layers, which may lead to improved local efficacy and a reduction in systemic exposure. The findings collectively support the hypothesis that ZnO-MSNs serve as an advanced and logical delivery platform for topical imiquimod in the management of basal cell carcinoma, effectively overcoming to traditional formulations, including poor tolerability, uncontrolled release, and inadequate dermal retention.

  Formulation and in Vitro Evaluation of Imiquimod-Loaded Zinc Oxide–Mesoporous Silica Hybrid Nanoparticles for Skin Cancer Therapy · 2026 · DOI

• underscore the pressing requirement for a more effective delivery system that optimizes drug localization, minimizes adverse effects, and ensures prolonged release at the intended site.

  Formulation and in Vitro Evaluation of Imiquimod-Loaded Zinc Oxide–Mesoporous Silica Hybrid Nanoparticles for Skin Cancer Therapy · 2026 · DOI

• Future investigations should focus on computational skin permeation modeling to extrapolate in vitro Strat-M® flux data to anticipated in vivo performance, human volunteer skin or permeation microdialysis methodology, and process scale-up feasibility assessments to advance this platform toward clinical translation.

  Development and Physicochemical Characterization of a Losartan Potassium Ethosomal Patch for Controlled Transdermal Delivery Applications · 2026 · DOI

• should several limitations Despite the encouraging findings of the present investigation, be acknowledged. The study primarily focused on preliminary cosmetic evaluation and did not include advanced physicochemical characterization such as rheological profiling, viscosity quantification, droplet size analysis, or instrumental texture assessment. The stability evaluation was limited to short-term physical observation, which does not establish long-term shelflife performance or accelerated environmental stability under varying temperature and humidity conditions. Although irritancy testing demonstrated favorable short-term skin compatibility, controlled clinical studies involving larger human populations were not conducted, limiting broader conclusions regarding long-term dermatological safety and efficacy. Quantitative efficacy endpoints such as objective skin hydration measurement, pigmentation reduction assessment, antimicrobial performance, and anti-inflammatory biomarker evaluation were not instrumentally assessed. Additionally, microbiological challenge preservative effectiveness and microbial resistance was not performed. Future investigations should incorporate advanced analytical characterization, extended stability studies, controlled dermatological trials, and to strengthen objective efficacy measurements scientific validation and support commercial development.

  FORMULATION AND EVALUATION OF HERBAL TURMERIC GLOW CREAM FOR TOPICAL SKINCARE APPLICATION · 2026 · DOI

• While microneedle technology is patient-friendly and less intrusive, it has great potential for drug administration in the future. The goal of ongoing research is to create smart microneedles www.wjpps.com │ Vol 15, Issue 6, 2026. │ ISO 9001:2015 Certified Journal │ 242 Gurbachan et al. World Journal of Pharmacy and Pharmaceutical Sciences with response to stimuli mechanisms that can deliver regulated and on-demand medication delivery. Real-time monitoring and customized treatment, particularly for diseases like diabetes mellitus, are anticipated to be made possible by integration with digital health technology like wearables and biosensors. The precision and scalability, and utility of microneedles—including gene delivery and nanoparticle-loaded ones—will be further enhanced by developments in 3D printing and nanotechnology. Additionally, efforts are being made to improve large-scale production for commercial usage, stability, and biocompatibility. Moreover, microneedles are probably going to be a big feature of immunization campaigns, especially for quick and painless mass immunization. 15. CONCLUSION A useful and creative remedy for the shortcomings of traditional transdermal treatment delivery systems is microneedle technology. Microneedles efficiently deliver many kinds of therapeutic substances, such as proteins, macromolecules, and vaccinations, as avoiding the stratum corneum. They are a better option than traditional methods because of their minimally invasive nature, increased patient compliance, and capacity to deliver controlled and targeted drug release. Additionally, improvements like smart microneedles, nanoparticle-loaded systems, and 3D printing have expanded their application in contemporary healthcare. Further research and development indicate that microneedles have an excellent chance of becoming a common and reliable drug delivery technique in the future, even though there are still problems with stability, large-scale production, and regulatory approval. 16. ACKNOWLEDGEMENT I am deeply thankful to all those who provided guidance and support throughout the completion of this work, particularly Dr Neeraj Pooni (Principal), lecturer Mrs. Damini Saini, and my guide, Ms. Shabnam, whose valuable guidance, encouragement, and continuous support made this work possible. 17. Declarations: Conflict of Interest: The authors declare no conflict of interest.

  RECENT ADVANCES IN MICRONEEDLE-BASED DRUG DELIVERY SYSTEMS: FABRICATION STRATEGIES, THERAPEUTIC APPLICATIONS AND FUTURE PERSPECTIVES · 2026 · DOI

• References Rapid dissolution, generating transient high local concentrations at the epidermal–dermal junction, thereby inducing early activation of cutaneous APCs Gradual hydration and dissolution, prolonging antigen exposure at local immune sites and supporting sustained DC uptake and enhanced initial T cell activation Limited mechanical strength; excessively rapid release, unfavorable for sustaining immune responses Limited long-term storage stability; relatively high demand for repeated administration (71) (72) Rapid dissolution in interstitial fluid, with drug deposition in the superficial dermis, promoting APC uptake and migration toward draining lymph nodes Sensitive to humidity; formulation stability and scalability remain challenging (73, 74) CMC (carboxymethyl cellulose) Two-step casting; dense arrays with controllable swelling behavior Swelling-induced formation of stable microchannels, enabling diffusion-driven sustained release, maintaining local immune stimulation and supporting continuous DC…

  Recent advances in dissolving microneedles for breast cancer immunotherapy: local delivery and tumor microenvironment remodeling · 2026 · DOI

• future and 2. Parveen R, Baboota S, Ali J, Ahuja A, Vasudev SS, Ahmad S. Oil based nanocarrier for improved oral delivery of silymarin: In vitro and in vivo studies. Int J Pharm 2011; 413(1-2): 245-53.

  A Review on Nanoemulsion in Improving the Bioavailability of Poorly Soluble Drugs · 2026 · DOI

• seeks production improve industries. The to The prospective applications of nanoemulsions in the food, cosmetics, healthcare, and agricultural sectors have sparked interest in them among scientists. They may contain phytochemicals and other bioactive substances used in the food and of pesticide the nanocarriers pharmacokinetics and absorption of herbal bioactives that are only weakly accessible by means of size reduction, encapsulation, and stability. A high level of drug delivery is the only way to improve therapeutic efficacy at the target site. Large molecular size and lipid solubilization are for biomembrane permeability in the case of herbal bioactives. One of the biggest challenges in making herbal medications is getting across the membrane with an improved pharmacokinetic profile. Lipid or oil-based nanocarriers may be the answer to these problems. They can improve bioavailability, reduce the impact of food on the rate of absorption of highly lipophilic compounds, and and gastrointestinal tract (GIT) absorption.

  A Review on Nanoemulsion in Improving the Bioavailability of Poorly Soluble Drugs · 2026 · DOI

• This study provides significant insights into the physico- chemical properties and biological effectiveness of NEG formulations, although it is essential to acknowledge specific limitations. The biological assays conducted—antioxidant, anti-inflammatory (LOX inhibition), and anti-tyrosinase activity—were executed in vitro utilizing isolated enzyme systems. While these models offer mechanistic insights, they fail to completely represent the complex biochemical and structural milieu of human skin. As a result, the extent to which these observed activities translate into tangible clinical outcomes is yet to be determined. An additional limitation of this study is the absence of in vitro release and ex vivo skin permeation/deposition studies. Although the physicochemical properties and biological activities of the formulations suggest potential for enhanced dermal deliv- ery, the lack of direct skin penetration data limits the abil- ity to establish a clear correlation between the observed in vitro findings and actual skin delivery performance. There- fore, conclusions regarding dermal retention and periocular localization remain hypothetical and should be interpreted with caution. Although the enzyme inhibition results (LOX and tyrosinase assays) indicate promising biological activ- ity, these findings are derived from simplified in vitro sys- tems and may not fully represent the complex physiological conditions of human skin. Therefore, any interpretation regarding their effectiveness in reducing hyperpigmentation or edema in vivo should be interpreted with caution. Another limitation is the absence of clinical evaluation. Although the formulations showed promising stability and Page 17 of 20 521 multifunctional biological activity in vitro, their actual performance on periorbital skin—such as effects on pig- mentation, vascular congestion, and edema—has not been validated. Additionally, the safety of long-term application around the sensitive periocular area needs thorough evalua- tion through standardized irritation and tolerability studies. Subsequent research should focus on ex vivo skin inves- tigations, in vitro release studies, ocular-periorbital safety evaluations, and controlled clinical trials to determine the therapeutic efficacy of the formulations in humans. Fur- thermore, mechanistic investigations into their effects on melanogenic signaling pathways (e.g., MITF, tyrosinase expression), inflammatory mediators, and microvascular physiology would clarify the combined or complementary effects indicated by the present findings. Such studies will support the translation of NEG technologies into clinically relevant cosmetic or dermatological applications.

  Development and Characterization of Herbal Extract-Loaded Nanoemulgels for Periorbital Hyperpigmentation and Edema: Antioxidant, Anti-inflammatory, and Anti-tyrosinase Activities · 2026 · DOI

• Despite its benefits, cold cream has certain limitations that circumscribe its universal connection. The slithery texture and heavy skin sense associated with traditional phrasings may reduce stoner adequacy, particularly among individualities with unctuous or acne-prone skin.[227] The occlusive nature of the cream may complicate follicular blockage, potentially leading to comedone susceptible individualities.[228] conformation in presence of water necessitates Another limitation is the threat of microbial impurity, as the effective preservation.[229] Traditional phrasings containing borax may also beget vexation in some druggies, egging the need for safer druthers in ultramodern phrasings.[230] likewise, cold cream generally exhibits limited penetration capability compared to advanced topical delivery the constituents.[231] bioavailability of therefore, while cold cream remains a precious topical expression, ultramodern advancements aim to retain its systems, which may circumscribe certain active www.ejpmr.com │ Vol 13, Issue 5, 2026. │ ISO 9001:2015 Certified Journal │ 75 Abhishek et al. European Journal of Pharmaceutical and Medical Research its downsides, advantages while minimizing broader acceptance and enhanced functionality.[232] icing provides occlusion, CONCLUSION Cold cream remains a abecedarian topical expression with enduring significance in both pharmaceutical and ornamental fields. Its water- in- oil painting conflation structure dragged effective moisturization, and protection of the skin hedge, making it especially salutary for dry and sensitive skin types. The expression’s simplicity, safety, and cost- effectiveness have contributed to its long- standing acceptance and wide use. ultramodern advancements in expression technology have significantly enhanced the performance of traditional cold cream. The objectification of new excipients, lipid- grounded delivery systems, natural bioactives, and bettered stabilizing agents has addressed before limitations similar as inordinate greasiness and have limited expanded the part of cold cream from a introductory moisturizer and a multifunctional to cosmeceutical delivery system. functionality. These advancements remedial In conclusion, cold cream successfully islands classical pharmaceutical expression generalities and contemporary technological inventions. Continued exploration and development are likely to further optimize its efficacity, consumer adequacy, and remedial eventuality, icing its sustained applicability in ultramodern dermatological and ornamental operations. REFERENCES 1. Aulton ME, Taylor K. Aulton’s Pharmaceutics: The Design and Manufacture of Medicines. 5th ed. London: Elsevier, 2018. 2. Allen LV, Ansel HC. Pharmaceutical Calculations. 15th ed. Philadelphia: Wolters Kluwer, 2020. 3. Lachman L, Lieberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. 4th ed. Mumbai: CBS Publishers, 2013. 4. United States Pharmacopeia–National Formulary.

  A REVIEW ON COLD CREAM · 2026 · DOI

• Metformin-incorporated proniosomes claim reduced gastrointestinal side effects and improved absorption with controlled release; however, direct comparison studies measuring gastrointestinal side effect incidence, absorption kinetics, and drug release profiles between proniosomal metformin and marketed extended-release metformin formulations in humans or appropriate GI models are absent.

  PRONIOSOMAL DRUG DELIVERY SYSTEMS: FABRICATION APPROACHES, MECHANISTIC INSIGHTS, AND MULTIFUNCTIONAL THERAPEUTIC APPLICATIONS · 2026 · DOI

• Proniosomal oxygen carrier applications for artificial hemoglobin delivery mention targeted delivery to ischemic regions but lack experimental validation; comparative biodistribution studies between proniosomal hemoglobin vesicles and conventional oxygen carriers in ischemia-reperfusion injury models are needed to quantify tissue oxygen delivery and therapeutic efficacy.

  PRONIOSOMAL DRUG DELIVERY SYSTEMS: FABRICATION APPROACHES, MECHANISTIC INSIGHTS, AND MULTIFUNCTIONAL THERAPEUTIC APPLICATIONS · 2026 · DOI

• The paper states proniosomes demonstrate favorable biocompatibility and non-toxicity profiles due to biocompatible materials, but the excerpt explicitly notes 'the possibility of toxicity cannot be entirely excl[uded]'; specific in vitro cytotoxicity assays, hemolysis studies, and systemic toxicity thresholds for different proniosomal lipid compositions and surfactants require systematic characterization.

  PRONIOSOMAL DRUG DELIVERY SYSTEMS: FABRICATION APPROACHES, MECHANISTIC INSIGHTS, AND MULTIFUNCTIONAL THERAPEUTIC APPLICATIONS · 2026 · DOI

• Hormone replacement therapy applications describe proniosomal formulations of levonorgestrel, letrozole, and estradiol with high encapsulation efficiencies (74-100%), but transdermal bioavailability, skin permeation kinetics, and long-term hormone plasma levels compared to conventional transdermal patches have not been characterized.

  PRONIOSOMAL DRUG DELIVERY SYSTEMS: FABRICATION APPROACHES, MECHANISTIC INSIGHTS, AND MULTIFUNCTIONAL THERAPEUTIC APPLICATIONS · 2026 · DOI

• Glibenclamide-loaded proniosomes demonstrated 73% blood glucose reduction in diabetes treatment, and glibenclamide proniosomal gel showed antioxidant protection in testicular tissues; however, no comparative in vivo efficacy studies exist between proniosomal glibenclamide and conventional glibenclamide formulations in diabetic animal models regarding glycemic control and oxidative stress markers.

  PRONIOSOMAL DRUG DELIVERY SYSTEMS: FABRICATION APPROACHES, MECHANISTIC INSIGHTS, AND MULTIFUNCTIONAL THERAPEUTIC APPLICATIONS · 2026 · DOI

• Proniosomal formulations for cardiology have shown improved bioavailability for statins, ACE inhibitors, and antihypertensive agents, but long-term pharmacokinetic and pharmacodynamic studies comparing proniosomal atorvastatin, captopril, and lisinopril against conventional formulations in animal cardiovascular disease models remain absent.

  PRONIOSOMAL DRUG DELIVERY SYSTEMS: FABRICATION APPROACHES, MECHANISTIC INSIGHTS, AND MULTIFUNCTIONAL THERAPEUTIC APPLICATIONS · 2026 · DOI

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