Needleless Administration of Advanced Therapies into the Skin Via the Appendages Using a Hypobaric Patch

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Apr 28

PMID 35482922

Authors

Faiza Benaouda

Ricardo Inacio

Chui Hua Lim

Haeeun Park

Thomas Pitcher

Mohamed A Alhnan

Mazen M S Aly

Khuloud T Al-Jamal

Ka-Lung Chan

Rikhav P Gala

Daniel Sebastia-Saez

Liang Cui

Tao Chen

Julie Keeble

Stuart A Jones

Affiliations

Soon will be listed here.

Abstract

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia. These changes allowed direct delivery of an H1N1 vaccine antigen and a diclofenac nanotherapeutic into the skin. Fluorescence imaging and infrared mapping of the skin showed needleless delivery via the appendages. The in vivo utility of the patch was demonstrated by a superior immunoglobulin G response to the vaccine antigen in mice compared to intramuscular injection and a 70% reduction in rat paw swelling in vivo over 5 h with diclofenac without skin histology changes.

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References

Rouphael N, Paine M, Mosley R, Henry S, McAllister D, Kalluri H . The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial. Lancet. 2017; 390(10095):649-658. PMC: 5578828. DOI: 10.1016/S0140-6736(17)30575-5. View

Ferreira S, Lorenzetti B, Poole S . Bradykinin initiates cytokine-mediated inflammatory hyperalgesia. Br J Pharmacol. 1993; 110(3):1227-31. PMC: 2175796. DOI: 10.1111/j.1476-5381.1993.tb13946.x. View

Shoji Y, Chichester J, Jones M, Manceva S, Damon E, Mett V . Plant-based rapid production of recombinant subunit hemagglutinin vaccines targeting H1N1 and H5N1 influenza. Hum Vaccin. 2011; 7 Suppl:41-50. DOI: 10.4161/hv.7.0.14561. View

Petchsangsai M, Rojanarata T, Opanasopit P, Ngawhirunpat T . The combination of microneedles with electroporation and sonophoresis to enhance hydrophilic macromolecule skin penetration. Biol Pharm Bull. 2014; 37(8):1373-82. DOI: 10.1248/bpb.b14-00321. View

Nair B, Taylor-Gjevre R . A Review of Topical Diclofenac Use in Musculoskeletal Disease. Pharmaceuticals (Basel). 2016; 3(6):1892-1908. PMC: 4033958. DOI: 10.3390/ph3061892. View

Takayama K, Hirose A, Suda I, Miyazaki A, Oguchi M, Onotogi M . Comparison of the anti-inflammatory and analgesic effects in rats of diclofenac-sodium, felbinac and indomethacin patches. Int J Biomed Sci. 2013; 7(3):222-9. PMC: 3614831. View

Vogt A, Combadiere B, Hadam S, Stieler K, Lademann J, Schaefer H . 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin. J Invest Dermatol. 2006; 126(6):1316-22. DOI: 10.1038/sj.jid.5700226. View

Cai X, Patel T, Woods A, Mesquida P, Jones S . Investigating the influence of drug aggregation on the percutaneous penetration rate of tetracaine when applying low doses of the agent topically to the skin. Int J Pharm. 2016; 502(1-2):10-7. DOI: 10.1016/j.ijpharm.2016.02.007. View

Lallow E, Jhumur N, Ahmed I, Kudchodkar S, Roberts C, Jeong M . Novel suction-based in vivo cutaneous DNA transfection platform. Sci Adv. 2021; 7(45):eabj0611. PMC: 8570601. DOI: 10.1126/sciadv.abj0611. View

10.

Cross S, Anderson C, Roberts M . Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies. Br J Clin Pharmacol. 1998; 46(1):29-35. PMC: 1873984. DOI: 10.1046/j.1365-2125.1998.00045.x. View

11.

Brown M, Martin G, Jones S, Akomeah F . Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv. 2006; 13(3):175-87. DOI: 10.1080/10717540500455975. View

12.

Rancan F, Papakostas D, Hadam S, Hackbarth S, Delair T, Primard C . Investigation of polylactic acid (PLA) nanoparticles as drug delivery systems for local dermatotherapy. Pharm Res. 2009; 26(8):2027-36. DOI: 10.1007/s11095-009-9919-x. View

13.

Alexander H, Cook T . Accounting for natural tension in the mechanical testing of human skin. J Invest Dermatol. 1977; 69(3):310-4. DOI: 10.1111/1523-1747.ep12507731. View

14.

Knorr F, Lademann J, Patzelt A, Sterry W, Blume-Peytavi U, Vogt A . Follicular transport route--research progress and future perspectives. Eur J Pharm Biopharm. 2008; 71(2):173-80. DOI: 10.1016/j.ejpb.2008.11.001. View

15.

Hengge U, Ruzicka T, Schwartz R, Cork M . Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2005; 54(1):1-15. DOI: 10.1016/j.jaad.2005.01.010. View

16.

Aguilar G, Svaasand L, Nelson J . Effects of hypobaric pressure on human skin: feasibility study for port wine stain laser therapy (part I). Lasers Surg Med. 2005; 36(2):124-9. DOI: 10.1002/lsm.20140. View

17.

Ehrl D, Heidekrueger P, Broer P, Erne H . Topical Negative Pressure Wound Therapy of Burned Hands: Functional Outcomes. J Burn Care Res. 2017; 39(1):121-128. DOI: 10.1097/BCR.0000000000000557. View

18.

Camacho N, West P, Torzilli P, Mendelsohn R . FTIR microscopic imaging of collagen and proteoglycan in bovine cartilage. Biopolymers. 2001; 62(1):1-8. DOI: 10.1002/1097-0282(2001)62:1<1::AID-BIP10>3.0.CO;2-O. View

19.

Cunha F, Lorenzetti B, Poole S, Ferreira S . Interleukin-8 as a mediator of sympathetic pain. Br J Pharmacol. 1991; 104(3):765-7. PMC: 1908235. DOI: 10.1111/j.1476-5381.1991.tb12502.x. View

20.

Leveque J, de Rigal J, Agache P, Monneur C . Influence of ageing on the in vivo extensibility of human skin at a low stress. Arch Dermatol Res. 1980; 269(2):127-35. DOI: 10.1007/BF00406532. View