Vega-Vásquez P, Mosier NS, Irudayaraj J. Nanoscale drug delivery systems: from medicine to agriculture. Front Bioeng Biotechnol. 2020;8:79. https://doi.org/10.3389/fbioe.2020.00079.
Article Google Scholar
Vargason AM, Anselmo AC, Mitragotri S. The evolution of commercial drug delivery technologies. Nat Biomed Eng. 2021. https://doi.org/10.1038/s41551-021-00698-w.
Mali AD, Bathe R, Patil M. An updated review on transdermal drug delivery systems. Int J Adv Sci Res. 2015;1(6):244–54. https://doi.org/10.7439/ijasr.v1i6.2243.
Article Google Scholar
Li C, Wang J, Wang Y, Gao H, Wei G, Huang Y, et al. Recent progress in drug delivery. Acta Pharm Sin B. 2019;9(6):1145–62. https://doi.org/10.1016/j.apsb.2019.08.003.
Article Google Scholar
Kumar JA, Pullakandam N, Prabu SL, Gopal V. Transdermal drug delivery system: An overview. Int J Pharm Sci Rev Res. 2010;3(2):49–54.
CAS Google Scholar
Roohnikan M, Laszlo E, Babity S, Brambilla DA. Snapshot of transdermal and tropical drug delivery research in Canada. Pharmaceutics. 2019;11(6):256. https://doi.org/10.3390/pharmaceutics11060256.
Article CAS Google Scholar
Peña-Juárez MC, Guadarrama-Escobar OR, Escobar-Chávez JJ. Transdermal delivery Systems for Biomolecules. J Pharm Innov. 2021;6:1–14.
Google Scholar
Ali H. Transdermal drug delivery system & patient compliance. MOJ Bioequiv Availab. 2017;3(2):47–8.
Google Scholar
Leppert W, Malec–Milewska M, Zajaczkowska R, Wordliczek J. Transdermal and Topical Drug Administration in the Treatment of Pain. Molecules. 2018;23(3):681.
Article Google Scholar
Akhter N, Singh V, Yusuf M, Khan RA. Non-invasive drug delivery technology: development and current status of transdermal drug delivery devices, techniques and biomedical applications. Biomed Tech. 2020;65(3):243–72. https://doi.org/10.1515/bmt-2019-0019.
Article CAS Google Scholar
Pires LR, Vinayakumar KB, Turos M, Miguel V, Gaspar J. A perspective on microneedle-based drug delivery and diagnostics in Paediatrics. J Pers Med. 2019;9(4):49. https://doi.org/10.3390/jpm9040049.
Article Google Scholar
Ruby PK, Pathak SM, Aggarwal D. Critical attributes of transdermal drug delivery system (TDDS) – a generic product development review. Drug Dev Ind Pharm. 2014;40(11):1421–8. https://doi.org/10.3109/03639045.2013.879720.
Article CAS Google Scholar
Ali S, Shabbir M, Shahid N. The structure of skin and transdermal drug delivery system - a review. Res J Pharm Tech. 2015;8(2):103–9. https://doi.org/10.5958/0974-360X.2015.00019.0.
Article Google Scholar
Wang M, Luo Y, Wang T, Wan C, Pan L, Pan S, et al. Artificial skin perception. Adv Mater. 2020;33:e2003014.
Article Google Scholar
Hutton AR, McCrudden MT, Larrañeta E, Donnelly RF. Influence of molecular weight on transdermal delivery of model macromolecules using hydrogel-forming microneedles: potential to enhance the administration of novel low molecular weight biotherapeutics. J Mater Chem B. 2020;8(19):4202–9. https://doi.org/10.1039/D0TB00021C.
Article CAS Google Scholar
Andrews SM, Jeong EH, Prausnitz MR. Transdermal delivery of molecules is limited by full epidermis, Not Just Stratum Corneum. Pharm Res. 2013;30(4):1099–109.
Article CAS Google Scholar
Chaulagain B, Jain A, Tiwari A, Verma A, Jain SK. Passive delivery of protein drugs through transdermal route. Artif Cells Nanomed Biotechnol. 2018;46(1):472–87. https://doi.org/10.1080/21691401.2018.1430695.
Article CAS Google Scholar
Uchechi O, Ogbonna J, Attama AA. Nanoparticles for dermal and transdermal drug delivery. In: Application of nanotechnology in drug delivery. Sezer AD: InTech C; 2014. p. 193–235.
Google Scholar
Zhou X, Hao Y, Yuan L, Pradhan S, Shrestha K, Pradhan O. Nano-formulations for transdermal drug delivery: a review. Chin Chem Lett. 2018;29(12):1713–24. https://doi.org/10.1016/j.cclet.2018.10.037.
Article CAS Google Scholar
Kováčik A, Kopečná M, Vávrová K. Permeation enhancers in transdermal drug delivery: benefits and limitations. Expert Opin Drug Deliv. 2020;17(2):145–55. https://doi.org/10.1080/17425247.2020.1713087.
Article CAS Google Scholar
Pawar PM, Solanki KP, Mandali VA. Recent advancements in transdermal drug delivery system. Int J Pharm Clin Res. 2018;10(3):65–73.
Google Scholar
Mujoriya R, Dhamande KA. Review on transdermal drug delivery system. Res J Sci Tech. 2011;3(4):227–31.
Google Scholar
Patel R, Patel A, Prajapati B, Shinde G, Dharamsi A. Transdermal drug delivery systems: A mini review. Int J Adv Res. 2018;6(5):891–900. https://doi.org/10.21474/IJAR01/7109.
Article Google Scholar
Kakar S, Singh R, Rani P. A review on transdermal drug delivery. Innoriginal Int J Sci. 2016;3(4):1–5.
Google Scholar
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 Deliv Transl Res. 2021. https://doi.org/10.1007/s13346-021-00898-6.
Dhal S, Pal K, Giri S. Transdermal delivery of gold nanoparticles by a soybean oil-based oleogel under iontophoresis. ACS Appl Bio Mater. 2020;3(10):7029–39. https://doi.org/10.1021/acsabm.0c00893.
Article CAS Google Scholar
Moarefian M, Davalos RV, Tafti DK, Acheniec LE, Jones CN. Modeling iontophoretic drug delivery in a microfluidic device. Lab Chip. 2020;20(18):3310–21. https://doi.org/10.1039/D0LC00602E.
Article CAS Google Scholar
Byrne JD, Yeh JJ, DeSimone JM. Use of iontophoresis for the treatment of cancer. J Control Release. 2018;284:144–51. https://doi.org/10.1016/j.jconrel.2018.06.020.
Article CAS Google Scholar
Sloan JB, Soltani K. Iontophoresis in dermatology: a review. J Am Acad Dermatol. 1986;15(4):671–84. https://doi.org/10.1016/S0190-9622(86)70223-5.
Article CAS Google Scholar
Park J, Lee H, Lim GS, Kim N, Kim D, Kim YC. Enhanced transdermal drug delivery by sonophoresis and simultaneous application of sonophoresis and iontophoresis. AAPS PharmSciTech. 2019;20(3):96. https://doi.org/10.1208/s12249-019-1309-z.
Article CAS Google Scholar
Seah BC, Teo BM. Recent advances in ultrasound-based transdermal drug delivery. Int J Nanomedicine. 2018;13:7749–63. https://doi.org/10.2147/IJN.S174759.
Article CAS Google Scholar
Nguyen HX, Banga AK. Electrically and ultrasonically enhanced transdermal delivery of methotrexate. Pharmaceutics. 2018;10(3):117. https://doi.org/10.3390/pharmaceutics10030117.
Article CAS Google Scholar
Escobar-Chávez JJ, Díaz-Torres R, Domínguez-Delgado CL, Rodríguez-Cruz IM, López-Arellano R, Hipólito EAM. Therapeutic applications of sonophoresis and sonophoretic devices. In: Percutaneous Penetration Enhancers Physical Methods in Penetration Enhancement. Springer-Verlag Berlin Heidelberg; 2017. p. 31–58.
Charoo NA, Rahman Z, Repka MA, Murthy SN. Electroporation: An avenue for transdermal drug delivery. Curr Drug Deliv. 2010;7(2):125–36. https://doi.org/10.2174/156720110791011765.
Article CAS Google Scholar
Chen X, Zhu L, Li R, Pang L, Zhu S, Ma J, et al. Electroporation-enhanced transdermal drug delivery: effects of logP, pKa, solubility and penetration time. Eur J Pharm Sci. 2020;151:105410. https://doi.org/10.1016/j.ejps.2020.105410.
Article CAS Google Scholar
Sokołowska E, Błachnio-Zabielska AU. A critical review of electroporation as a plasmid delivery system in mouse skeletal muscle. Int J Mol Sci. 2019;20(11):2776. https://doi.org/10.3390/ijms20112776.
Article CAS Google Scholar
Dermol-Černe J, Pirc E, Miklavčič D. Mechanistic view of skin electroporation – models and dosimetry for successful applications: an expert review. Expert Opin Drug Deliv. 2020;17(5):689–704. https://doi.org/10.1080/17425247.2020.1745772.
Article Google Scholar
Escobar-Chávez JJ, Bonilla-Martínez D, Villegas-González MA, Revilla-Vázquez AL. Electroporation as an efficient physical enhancer for skin drug delivery. J Clin Pharmacol. 2009;49(11):1262–83. https://doi.org/10.1177/0091270009344984.
Article CAS Google Scholar
Lin CH, Aljuffali IA, Fang JY. Lasers as an approach for promoting drug delivery via skin. Expert Opin Drug Deliv. 2014;11(4):599–614. https://doi.org/10.1517/17425247.2014.885501.
Article CAS Google Scholar
Lee S, Kollias N, McAuliffe DJ, Flotte TJ, Doukas AG. Topical drug delivery in humans with a single photomechanical wave. Pharm Res. 1999;16(11):1717–21. https://doi.org/10.1023/A:1018954015441.
Article CAS Google Scholar
Agrawal S, Gandhi SN, Gurgar P, Saraswathy N. Microneedles: An advancement to transdermal drug delivery system approach. J Appl Pharm Sci. 2020;10(3):149–59.
Article CAS Google Scholar
Zhao Z, Chen Y, Shi Y. Microneedles: a potential strategy in transdermal delivery and application in the management of psoriasis. RSC Adv. 2020;10(24):14040–9. https://doi.org/10.1039/D0RA00735H.
Article CAS Google Scholar
Jung JH, Jin SG. Microneedle for transdermal drug delivery: current trends and fabrication. J Pharm Investig. 2021. https://doi.org/10.1007/s40005-021-00512-4.
Shakya AK, Ingrole RSJ, Joshi G, Uddin MJ, Anvari S, Davis CM, et al. Microneedles coated with peanut allergen enable desensitization of peanut sensitized mice. J Control Release. 2019;314:38–47. https://doi.org/10.1016/j.jconrel.2019.09.022.
Article CAS Google Scholar
Lim J, Tahk D, Yu J, Min DH, Jeon NL. Design rules for a tunable merged-tip microneedle. Microsyst Nanoeng. 2018;4(1):1–10.
Article CAS Google Scholar
Dardano P, Caliò A, Palma VD, Bevilacqua MF, Matteo AD, Stefano LD. A photolithographic approach to polymeric microneedles array fabrication. Materials. 2015;8(12):8661–73. https://doi.org/10.3390/ma8125484.
Article CAS Google Scholar
Han D, Morde RS, Mariani S, Mattina AAL, Vignali E, Yang C, et al. 4D printing of a bioinspired microneedle array with backward-facing barbs for enhanced tissue adhesion. Adv Funct Mater. 2020;30(11):1909197. https://doi.org/10.1002/adfm.201909197.
Article CAS Google Scholar
Xiao Z, Li X, Zhang P, Wang Y. Research of polymeric microneedles for transdermal drug delivery. Progress Chem. 2017;29(12):1518.
Google Scholar
Balmert SC, Carey CD, Falo GD, Sethi SK, Erdos G, Korkmaz E, et al. Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination. J Control Release. 2020;317:336–46. https://doi.org/10.1016/j.jconrel.2019.11.023.
Article CAS Google Scholar
Kim HM, Lim YY, An JH, Kim MN, Kim BJ. Transdermal drug delivery using disk microneedle rollers in a hairless rat model. Int J Dermatol. 2012;51(7):859–63. https://doi.org/10.1111/j.1365-4632.2011.05343.x.
Article CAS Google Scholar
Li K, Yoo KH, Byun HJ, Lim YY, Kim MN, Hong HK, et al. The microneedle roller is an effective device for enhancing transdermal drug delivery. Int J Dermatol. 2012;51(9):1137–9. https://doi.org/10.1111/j.1365-4632.2010.04703.x.
Article CAS Google Scholar
Bariya SH, Gohel MC, Mehta TA, Sharma OP. Microneedles: an emerging transdermal drug delivery system. J Pharm Pharmacol. 2012;64(1):11–29.
Article CAS Google Scholar
Lee YS, Kang TG, Cho HR, Lee GJ, Park OK, Kim SY, et al. Localized delivery of Theranostic nanoparticles and high-energy photons using microneedles-on-bioelectronics. Adv Mater. 2021;33(24):2100425. https://doi.org/10.1002/adma.202100425.
Article CAS Google Scholar
Du H, Liu P, Zhu J, Li Y, Zhang L, Zzhu J, et al. Hyaluronic acid-based dissolving microneedle patch loaded with methotrexate for improved treatment of psoriasis. ACS Appl Mater Interfaces. 2019;11(46):43588–98. https://doi.org/10.1021/acsami.9b15668.
Article CAS Google Scholar
Alkilani AZ, Mccrudden MTC, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015;7(4):438–70. https://doi.org/10.3390/pharmaceutics7040438.
Article CAS Google Scholar
Amjadi M, Mostaghaci B, Sitti M. Recent advances in skin penetration enhancers for transdermal gene and drug delivery. Curr Gene Ther. 2017;17(2):139–46.
Article CAS Google Scholar
Li Y, Guo L, Lu W. Laser ablation-enhanced transdermal drug delivery. Photonics Lasers Med. 2013;2(4):315–22.
Article Google Scholar
Szunerits S, Boukherroub R. Heat: a highly efficient skin enhancer for transdermal drug delivery. Front Bioeng Biotechnol. 2018;6:15. https://doi.org/10.3389/fbioe.2018.00015.
Article Google Scholar
Parhi R, Mandru A. Enhancement of skin permeability with thermal ablation techniques: concept to commercial products. Drug Delivery Translat Res. 2021;11:817-41.
Babaie S, Del Bakhshayesh AR, Ha JW, Hamishehkar H. Invasome: A novel nanocarrier for transdermal drug delivery. Nanomaterials. 2020;10(2):341. https://doi.org/10.3390/nano10020341.
Article CAS Google Scholar
Palac Z, Engesland A, Flaten GE, Škalko-Basnet N, Filipović-Grčić J, Vanić Ž. Liposomes for (trans)dermal drug delivery: the skin-PVPA as a novel in vitro stratum corneum model in formulation development. J Liposome Res. 2014;24(4):313–22. https://doi.org/10.3109/08982104.2014.899368.
Article CAS Google Scholar
Rajan R, Jose S, Mukund VP, Vasudevan DT. Transferosomes-a vesicular transdermal delivery system for enhanced drug permeation. J Adv Pharm Technol Res. 2011;2(3):138–43. https://doi.org/10.4103/2231-4040.85524.
Article CAS Google Scholar
Zhang Z, Liu Y, Chen Y, Li L, Lan P, He D, et al. Transdermal delivery of 5-aminolevulinic acid by nanoethosome gels for photodynamic therapy of hypertrophic scars. ACS Appl Mater Interfaces. 2019;11(4):3704–14. https://doi.org/10.1021/acsami.8b17498.
Article CAS Google Scholar
Stanekzai A, Sudhakar CK, Zhakfar AM, Karan VS. Recent approaches in transdermal drug delivery system. Res J Pharm Tech. 2019;12(9):4550–8. https://doi.org/10.5958/0974-360X.2019.00783.2.
Article Google Scholar
Hadgraft J, Lane ME. Passive transdermal drug delivery systems. Am J Drug Deliv. 2006;4(3):153–60. https://doi.org/10.2165/00137696-200604030-00003.
Article CAS Google Scholar
Gandhi K, Dahiya A, Monika LT, Singh K. Transdermal drug delivery – a review. Int J Res Pharm Sci. 2012;3(3):379–88.
Google Scholar
Dhal S, Gavara RR, Pal K, Banerjee I, Mishra M, Giri S. Facile transdermal delivery of upconversion nanoparticle by iontophoresis-responsive magneto-upconversion oleogel. Nano Express. 2020;1(1):010012. https://doi.org/10.1088/2632-959X/ab81e1.
Article Google Scholar
Jeong WY, Kim SD, Lee SY, Lee HS, Han DW, Yang SY, et al. Transdermal delivery of Minoxidil using HA-PLGA nanoparticles for the treatment in alopecia. Biomater Res. 2019;23(1):16. https://doi.org/10.1186/s40824-019-0164-z.
Article CAS Google Scholar
Lee SY, Kang MS, Jeong WY, Han DW, Kim KS. Hyaluronic acid-based theranostic nanomedicines for targeted cancer therapy. Cancers. 2020;12(4):940. https://doi.org/10.3390/cancers12040940.
Article CAS Google Scholar
Jijie R, Barras A, Boukherroub R, Szunerits S. Nanomaterials for transdermal drug delivery: beyond the state of the art of liposomal structures. J Mater Chem B. 2017;5(44):8653–75. https://doi.org/10.1039/C7TB02529G.
Article CAS Google Scholar
Ali A, Ahmad U. Nanoemulsion as a vehicle in transdermal drug delivery. Insights Biomed. 2018;3:15.
CAS Google Scholar
Halnor V, Pande V, Borawake D, Nagare H. Nanoemulsion: A novel platform for drug delivery system. J Mat Sci Nanotechol. 2018;6(1):104.
Google Scholar
Benson HA, Grice JE, Mohammed Y, Namjoshi S, Roberts MS. Topical and transdermal drug delivery: from simple potions to smart technologies. Curr Drug Deliv. 2019;16(5):444–60. https://doi.org/10.2174/1567201816666190201143457.
Article CAS Google Scholar
Ramadon D, McCrudden MT, Courtenay AJ, Donnelly RF. Enhancement strategies for transdermal drug delivery systems: current trends and applications. Drug Deliv Transl Res. 2021;20:1–34.
Google Scholar
Lee HJ, Song CY, Baik SM, Kim DY, Hyeon TG, Kim DH. Device-assisted transdermal drug delivery. Adv Drug Deliv Rev. 2018;127:35–45. https://doi.org/10.1016/j.addr.2017.08.009.
Article CAS Google Scholar
Bird D, Ravindra NM. Transdermal drug delivery and patches - an overview. Med Devices Sens. 2020;3(6):e10069.
Article Google Scholar
Hanbali OA, Khan HS, Sarfraz M, Arafat M, Ijaz S, Hameed A. Transdermal patches: design and current approaches to painless drug delivery. Acta Pharma. 2019;69(2):197–215. https://doi.org/10.2478/acph-2019-0016.
Article CAS Google Scholar
Escobar-Chávez JJ, Díaz-Torres R, Rodríguez-Cruz IM, Domínguez-Delgado CL, Morales RS, Ángeles-Anguiano E, et al. Nanocarriers for transdermal drug delivery. Res Rep Transdermal Drug Delivery. 2012;1:3–17.
Article Google Scholar
Patra JK, Das G, Fraceto LF, Campos EV, Del Pilar R-TM, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018;16(1):71. https://doi.org/10.1186/s12951-018-0392-8.
Article CAS Google Scholar
Buhecha MD, Lansley AB, Somavarapu S, Pannala AS. Development and characterization of PLA nanoparticles for pulmonary drug delivery: co-encapsulation of theophylline and budesonide, a hydrophilic and lipophilic drug. J Drug Deliv Sci Technol. 2019;53:101128. https://doi.org/10.1016/j.jddst.2019.101128.
Article CAS Google Scholar
Raza R, Mittai A, Kumar P, Alam S, Prakash S, Chauhan N. Approaches and evaluation of transdermal drug delivery system. Int J Drug Dev Res. 2015;7(1):222–33.
CAS Google Scholar
Sheth NS, Mistry RB. Formulation and evaluation of transdermal patches and to study permeation enhancement effect of eugenol. J. Appl. Pharm. Sci. 2011;1(3):96–101.
Google Scholar
Salamanca CH, Barrera-Ocampo A, Lasso JC, Camacho N, Yarce CJ. Franz diffusion cell approach for pre-formulation characterisation of ketoprofen semi-solid dosage forms. Pharmaceutics. 2018;10(3):148. https://doi.org/10.3390/pharmaceutics10030148.
Article CAS Google Scholar
Lee JD, Kim JY, Jang HJ, Lee BM, Kim KB. Percutaneous permeability of 1-phenoxy-2-propanol, a preservative in cosmetics. Regul Toxicol Pharmacol. 2019;103:56–62. https://doi.org/10.1016/j.yrtph.2019.01.002.
Article CAS Google Scholar
Rajithaa P, Shammika P, Aiswarya S, Gopikrishnan A, Jayakumar R, Sabitha M. Chaulmoogra oil based methotrexate loaded topical nanoemulsion for the treatment of psoriasis. J Drug Deliv Sci Technol. 2019;49:463–76. https://doi.org/10.1016/j.jddst.2018.12.020.
Article CAS Google Scholar
Escobar-Chávez JJ, Merino-Sanjuán V, López-Cervantes M, Urban-Morlan Z, Piñón-Segundo E, Quintanar-Guerrero D, et al. The tape-stripping technique as a method for drug quantification in skin. J Pharm Pharm Sci. 2008;11(1):104–30. https://doi.org/10.18433/J3201Z.
Article Google Scholar
Russell LM, Guy RH. Novel imaging method to quantify stratum corneum in dermatopharmacokinetic studies: proof-of-concept with acyclovir formulations. Pharm Res. 2012;29(12):3362–72. https://doi.org/10.1007/s11095-012-0831-4.
Article CAS Google Scholar
Gu Y, Yang M, Tang X. Lipid nanoparticles loading triptolide for transdermal delivery: mechanisms of penetration enhancement and transport properties. J Nanobiotechnol. 2018;16(1):1–14.
Article Google Scholar
Ahn J, Kim KH, Choe K, Lim JH, Lee SK, Kim YS, et al. Quantitative two-photon microscopy imaging analysis of human skin to evaluate enhanced transdermal delivery by hybrid-type multi-lamellar nanostructure. Biomed Opt Express. 2018;9(8):3974–82. https://doi.org/10.1364/BOE.9.003974.
Article CAS Google Scholar
Berekméri A, Tiganescu A, Alase AA, Vital E, Stacey M, Wittmann M. Non-invasive approaches for the diagnosis of autoimmune/autoinflammatory skin diseases-a focus on psoriasis and lupus erythematosus. Front Immunol. 2019;10:1931. https://doi.org/10.3389/fimmu.2019.01931.
Article CAS Google Scholar
Ashtikar M, Matthäus C, Schmitt M, Krafft C, Fahr A, Popp J. Non-invasive depth profile imaging of the stratum corneum using confocal raman microscopy: first insights into the method. Eur J Pharm Sci. 2013;50(5):601–8. https://doi.org/10.1016/j.ejps.2013.05.030.
Article CAS Google Scholar
Zhang LW, Monteiro-Riviere NA. Use of confocal microscopy for nanoparticle drug delivery through skin. J Biomed Opt. 2012;18(6):061214. https://doi.org/10.1117/1.JBO.18.6.061214.
Article Google Scholar
Page 2
Method
Advantages
Disadvantages
Ref.
Active Delivery
Iontophoresis
• Improving the delivery of polar molecules as well as high molecular weight compounds • Faster and easier administration
• Enabling continuous or pulsatile delivery of drug
• Risk of burns if electrodes are used improperly • Difficulty stabilizing the therapeutic agent in the vehicle
• Complexity of the drug release system
[25,26,27,28,29]
Sonophoresis
• Allows strict control of transdermal diffusion rates • In many cases, greater patient approval • Less risk of systemic absorption • Helpful to break up blood clots
• Not immensely sensitizing
• Can be prolonged to administer • Minor tingling, irritation and burning
• SC must be unbroken for effective drug penetration
[30,31,32,33]
Electroporation
• Highly effective, reproducible, directed drug transfer • Permits rapid termination of drug delivery through termination
• Not immensely sensitizing
• Impossible to use on a large area • Can be disturb the cargo if high voltage is uesd • Possibility of cell damage
• Relatively nonspecific
[34,35,36]
Photomechanical waves
• Can improve transfer of molecules across the plasma membrane of cells in vitro without loss of viability • Not appear to cause injury to the viable skin
• Do not cause pain or discomfort
• Lack of human clinical data
[37,38,39,40]
Microneedle
• Painless administration of the active pharmaceutical ingredient • Faster healing at injection site • No fear of needle
• Specific skin area can be targeted for proper drug delivery
• Lower dosing accuracy than hypodermic needles • Penetration depth of various particles depending on the skin layer
• Possibility of venous collapse due to repeated injections
[41,42,43,44,45,46,47,48,49,50,51,52,53,54]
Thermal ablation
• Avoid the pain, bleeding, and infection • Can remove SC selectively without damaging deeper tissues • Better control and reproducibility
• Low cost and disposable device
• Structural changes in the skin must be evaluated • Existing concerns about the use of extreme temperatures and the logistics of such devices
[55,56,57,58,59]
Passive delivery
Vesicles
• Accomplish sustained drug release behavior • Control the absorption rate through a multilayered structure
• Chemically unstable • Expensive of formulations
• Limitation of drug loading
[60,61,62,63]
Polymeric nanoparticles
• Accomplish targeted and controlled release behavior • High mechanical strength and non-deformability • Can be made of various biodegradable materials • Can be loaded both hydrophilic and hydrophobic drugs
• Can avoid the immune system due to small size
• Difficult to break down • Not enough toxicological assessment has been done
• Some processes are difficult to scale up
[64,65,66,67,68,69,70]
Nanoemulsion
• Long-term thermodynamic stability • Excellent wettability • High solubilization capacity and physical stability
• Possible to formulate it in variety of formulations
• Requires large concentration of emulsifiers • Limited solubilizing capacity for high-melting substances
• Variable kinetics of distribution processes and clearance
