Generic placeholder image

Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Review Article

Invasomes for Enhanced Delivery through the Skin: Evaluation of Systems to Meet with Clinical Challenges

Author(s): Ravi Shankar, Prabhat K. Upadhyay and Manish Kumar*

Volume 9, Issue 5, 2021

Published on: 28 December, 2021

Page: [317 - 325] Pages: 9

DOI: 10.2174/2211738510666211220142126

Price: $65

Abstract

Background: Portage of therapeutic agents directly to the skin (cutaneous/dermal delivery) is the preferable approach in mitigating and curing a variety of skin manifestations, including itching, eczema, acne, psoriasis keratinization, and skin cancer. Dermal delivery reduces side effects associated with systemic therapy and allows maximum utilization of the available doses. Invasomes are the next generation of liposomes with greater flexibility, elasticity, and permeability through the skin than liposomes and ethosomes.

Objective: This review article highlights various aspects of invasomes, including the structure and composition of invasomes, methods of preparation of invasomes, the mechanism involved in better penetration through the skin, key parameters to be considered for effective permeation, therapeutic applications of invasomes as novel drug delivery systems, and future development and challenges.

Methods: The authors have reviewed various primary and secondary sources, including PUBMED, SCIENCE DIRECT, INFORMA, and patents.com, to collect information on various aspects of invasomes.

Results and Conclusion: Invasomes are novel vesicular drug delivery systems that have been used for dermal delivery of drugs for various therapeutic applications. These novel carriers have great ability, and their properties can be highly modulated by varying their composition and concentration of terpenes. Based on all the research reports gathered, it is well proven that these systems have a much higher potential for delivering drugs for skin manifestations and could expand the opportunities for treating various dermatological issues, increasing day by day.

Keywords: Cutaneous, dermal, liposome, invasome, permeation, vesicular systems.

Graphical Abstract
[1]
Higuchi T. Physical-chemical analysis of percutaneous absorption process from creams and ointments. J Soc Cosmet Chem 1960; 11: 85-97.
[2]
Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv 2006; 13(3): 175-87.
[http://dx.doi.org/10.1080/10717540500455975] [PMID: 16556569]
[3]
Barry BW, Smith E, Maibach HI. Penetration enhancer classification. 2nd ed. Percutaneous penetration enhancers. 2nd ed. United Kingdom: Taylor and Francis Group 1995; pp. 3-16.
[4]
Bouwstra JA, Honeywell-Nguyen PL. Skin structure and mode of action of vesicles. Adv Drug Deliv Rev 2002; 54(54)(Suppl. 1): S41-55.
[http://dx.doi.org/10.1016/S0169-409X(02)00114-X] [PMID: 12460715]
[5]
Cancel LM, Tarbell JM, Ben-Jebria A. Fluorescein permeability and electrical resistance of human skin during low frequency ultrasound application. J Pharm Pharmacol 2004; 56(9): 1109-18.
[http://dx.doi.org/10.1211/0022357044193] [PMID: 15324479]
[6]
Liu H, Li S, Wang Y, Yao H, Zhang Y. Effect of vehicles and enhancers on the topical delivery of cyclosporin A. Int J Pharm 2006; 311(1-2): 182-6.
[http://dx.doi.org/10.1016/j.ijpharm.2005.12.029] [PMID: 16439077]
[7]
Barry BW. Breaching the skin’s barrier to drugs. Nat Biotechnol 2004; 22(2): 165-7.
[http://dx.doi.org/10.1038/nbt0204-165] [PMID: 14755286]
[8]
Pierre MBR, Dos Santos Miranda Costa I. Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Arch Dermatol Res 2011; 303(9): 607-21.
[http://dx.doi.org/10.1007/s00403-011-1166-4] [PMID: 21805180]
[9]
Wang J, Yuan Y, Liu C, Zhu D, Shen X, Yang B. Preparation and pharmaceutical/pharmacodynamic evaluation of topical brucine-loaded liposomal hydrogel. J Mater Sci Mater Med 2009; 20(10): 2075-84.
[http://dx.doi.org/10.1007/s10856-009-3773-6] [PMID: 19459034]
[10]
Gupta R, Dwadasi BS, Rai B, Mitragotri S. Effect of chemical permeation enhancers on skin permeability: in silico screening using molecular dynamics simulations. Sci Rep 2019; 9(1): 1456.
[http://dx.doi.org/10.1038/s41598-018-37900-0] [PMID: 30728438]
[11]
Bharkatiya M, Nema RK. Skin penetration enhancement techniques. J Young Pharm 2009; 1(2): 110-5.
[http://dx.doi.org/10.4103/0975-1483.55741]
[12]
Fireman S, Toledano O, Neimann K, Loboda N, Dayan N. A look at emerging delivery systems for topical drug products. Dermatol Ther 2011; 24(5): 477-88.
[http://dx.doi.org/10.1111/j.1529-8019.2012.01464.x] [PMID: 22353154]
[13]
Lee RW, Shenoy DB, Sheel R, Kulkarni Vithal S, Eds. Micellar nanoparticles: Applications for topical and passive transdermal drug delivery. Kulkarni VS, ed. Handbook of non-invasive drug delivery systems Burlington: Elsevier Inc 2009; pp. 37-58.
[14]
Vogt A, Wischke C, Neffe AT, Ma N, Alexiev U, Lendlein A. Nanocarriers for drug delivery into and through the skin - Do existing technologies match clinical challenges? J Control Release 2016; 242: 3-15.
[http://dx.doi.org/10.1016/j.jconrel.2016.07.027] [PMID: 27449743]
[15]
Dragicevic N, Maibach HI. Percutaneous penetration enhancers chemical methods in penetration enhancement. Berlin, Germany: Springer 2016.
[http://dx.doi.org/10.1007/978-3-662-47862-2]
[16]
Sinico C, Fadda AM. Vesicular carriers for dermal drug delivery. Expert Opin Drug Deliv 2009; 6(8): 813-25.
[http://dx.doi.org/10.1517/17425240903071029] [PMID: 19569979]
[17]
Cevc G, Schätzlein A, Blume G. Transdermal drug carriers: Basic properties, optimization and transfer efficiency in the case of epicutaneously applied peptides. J Control Release 1995; 36: 3-16.
[http://dx.doi.org/10.1016/0168-3659(95)00056-E]
[18]
Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug Carrier Syst 1996; 13(3-4): 257-388.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v13.i3-4.30] [PMID: 9016383]
[19]
Mezei M, Gulasekharam V. Liposomes- a selective drug delivery system for the topical route of administration. Lotion dosage form. Life Sci 1980; 26(18): 1473-7.
[http://dx.doi.org/10.1016/0024-3205(80)90268-4] [PMID: 6893068]
[20]
Škalko N, Cajkovac M, Jalšenjak I. Liposomes with clindamycin hydrochloride in the therapy of acne vulgaris. Int J Pharm 1992; 85: 97-101.
[http://dx.doi.org/10.1016/0378-5173(92)90138-R]
[21]
Schaeffer HE, Krohn DL. Liposomes in topical drug delivery. Invest. The topical route of administration I. Lotion dosage form. Life Sci 1982; 26: 1473-7.
[22]
Lieberman HA, Rieger MM, Banker GS. Pharmaceutical dosage forms: Disperse systems in Three. New York, NY, U.S.A.: Marcel Dekker 1998.
[http://dx.doi.org/10.1201/9781420000955]
[23]
El Maghraby GM, Williams AC, Barry BW. Skin delivery of oestradiol from lipid vesicles: importance of liposome structure. Int J Pharm 2000; 204(1-2): 159-69.
[http://dx.doi.org/10.1016/S0378-5173(00)00493-2] [PMID: 11012000]
[24]
El Maghraby GM, Williams AC, Barry BW. Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro. J Pharm Pharmacol 2001; 53(8): 1069-77.
[http://dx.doi.org/10.1211/0022357011776450] [PMID: 11518016]
[25]
Chen M, Liu X, Fahr A. Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: in vitro study with finite and infinite dosage application. Int J Pharm 2011; 408(1-2): 223-34.
[http://dx.doi.org/10.1016/j.ijpharm.2011.02.006] [PMID: 21316430]
[26]
Ota Y, Hamada A, Nakano M, Saito H. Evaluation of percutaneous absorption of midazolam by terpenes. Drug Metab Pharmacokinet 2003; 18(4): 261-6.
[http://dx.doi.org/10.2133/dmpk.18.261] [PMID: 15618744]
[27]
Puglia C, Bonina F, Trapani G, Franco M, Ricci M. Evaluation of in vitro percutaneous absorption of lorazepam and clonazepam from hydro-alcoholic gel formulations. Int J Pharm 2001; 228(1-2): 79-87.
[http://dx.doi.org/10.1016/S0378-5173(01)00806-7] [PMID: 11576770]
[28]
Vaddi HK, Ho PC, Chan YW, Chan SY. Terpenes in ethanol: haloperidol permeation and partition through human skin and stratum corneum changes. J Control Release 2002; 81(1-2): 121-33.
[http://dx.doi.org/10.1016/S0168-3659(02)00057-3] [PMID: 11992685]
[29]
Verma DD, Fahr A. Synergistic penetration enhancement effect of ethanol and phospholipids on the topical delivery of cyclosporin A. J Control Release 2004; 97(1): 55-66.
[http://dx.doi.org/10.1016/j.jconrel.2004.02.028] [PMID: 15147804]
[30]
L Lakshmi P, Kalpana B, Prasanthi D. Invasomes-novel vesicular carriers for enhanced skin permeation. Syst Rev Pharm 2013; 4: 26-30.
[http://dx.doi.org/10.4103/0975-8453.135837]
[31]
Aqil M, Ahad A, Sultana Y, Ali A. Status of terpenes as skin penetration enhancers. Drug Discov Today 2007; 12(23-24): 1061-7.
[http://dx.doi.org/10.1016/j.drudis.2007.09.001] [PMID: 18061886]
[32]
Singla V, Saini S, Singh G, Rana AC, Vaibhav J. Penetration enhancers: a novel strategy for enhancing transdermal drug delivery. Int Res J Pharm 2011; 2: 32-6.
[33]
Cornwell PA, Barry BW. Sesquiterpene components of volatile oils as skin penetration enhancers for the hydrophilic permeant 5-fluorouracil. J Pharm Pharmacol 1994; 46(4): 261-9.
[http://dx.doi.org/10.1111/j.2042-7158.1994.tb03791.x] [PMID: 8051608]
[34]
Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev 2004; 56(5): 603-18.
[http://dx.doi.org/10.1016/j.addr.2003.10.025] [PMID: 15019749]
[35]
Dragicevic-Curic N, Gräfe S, Gitter B, Fahr A. Efficacy of temoporfin-loaded invasomes in the photodynamic therapy in human epidermoid and colorectal tumour cell lines. J Photochem Photobiol B 2010; 101(3): 238-50.
[http://dx.doi.org/10.1016/j.jphotobiol.2010.07.009] [PMID: 20797872]
[36]
Badran MM, Kuntsche J, Fahr A. Skin penetration enhancement by a microneedle device (Dermaroller) in vitro: dependency on needle size and applied formulation. Eur J Pharm Sci 2009; 36(4-5): 511-23.
[http://dx.doi.org/10.1016/j.ejps.2008.12.008] [PMID: 19146954]
[37]
Haag SF, Fleige E, Chen M, et al. Skin penetration enhancement of core-multishell nanotransporters and invasomes measured by electron paramagnetic resonance spectroscopy. Int J Pharm 2011; 416(1): 223-8.
[http://dx.doi.org/10.1016/j.ijpharm.2011.06.044] [PMID: 21745556]
[38]
Dragicevic-Curic N, Friedrich M, Petersen S, et al. Assessment of fluidity of different invasomes by electron spin resonance and differential scanning calorimetry. Int J Pharm 2011; 412(1-2): 85-94.
[http://dx.doi.org/10.1016/j.ijpharm.2011.04.020] [PMID: 21527323]
[39]
Dayan N, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomaterials 2000; 21(18): 1879-85.
[http://dx.doi.org/10.1016/S0142-9612(00)00063-6] [PMID: 10919691]
[40]
Verma P, Pathak K. Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomedicine 2012; 8(4): 489-96.
[http://dx.doi.org/10.1016/j.nano.2011.07.004] [PMID: 21839053]
[41]
Valenta C, Janisch M. Permeation of cyproterone acetate through pig skin from different vehicles with phospholipids. Int J Pharm 2003; 258(1-2): 133-9.
[http://dx.doi.org/10.1016/S0378-5173(03)00180-7] [PMID: 12753760]
[42]
Kumar L, Verma S, Singh K, Prasad DN, Jain AK. Ethanol based vesicular carriers in transdermal drug delivery: nanoethosomes and transethosomes in focus. NanoWorld J 2016; 2(3): 41-51.
[http://dx.doi.org/10.17756/nwj.2016-030]
[43]
Cornwell PA, Barry BW, Bouwstra JA, Gooris GS. Modes of action of terpene penetration enhancers in human skin; differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies. Int J Pharm 1996; 127: 9-26.
[http://dx.doi.org/10.1016/0378-5173(95)04108-7]
[44]
Kamran M, Ahad A, Aqil M, Imam SS, Sultana Y, Ali A. Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: in vitro characterization and in vivo pharmacokinetic assessment. Int J Pharm 2016; 505(1-2): 147-58.
[http://dx.doi.org/10.1016/j.ijpharm.2016.03.030] [PMID: 27005906]
[45]
Cui Y, Li L, Zhang L, et al. Enhancement and mechanism of transdermal absorption of terpene-induced propranolol hydrochloride. Arch Pharm Res 2011; 34(9): 1477-85.
[http://dx.doi.org/10.1007/s12272-011-0909-2] [PMID: 21975809]
[46]
Zhou W, He S, Yang Y, Jian D, Chen X, Ding J. Formulation, characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma. Drug Dev Ind Pharm 2015; 41(7): 1109-19.
[http://dx.doi.org/10.3109/03639045.2014.931968] [PMID: 25151873]
[47]
Verma DD, Verma S, McElwee KJ, Freyschmidt-Paul P, Hoffman R, Fahr A. Treatment of alopecia areata in the DEBR model using cyclosporin A lipid vesicles. Eur J Dermatol 2004; 14(5): 332-8.
[PMID: 15358573]
[48]
Dragicevic-Curic N, Scheglmann D, Albrecht V, Fahr A. Temoporfin-loaded invasomes: development, characterization and in vitro skin penetration studies. J Control Release 2008; 127(1): 59-69.
[http://dx.doi.org/10.1016/j.jconrel.2007.12.013] [PMID: 18281119]
[49]
Maira MS, Pearson MA, Fabbro D, Echeverría CG. Cancer Biology. Comp Med Chem II 2007; 7: 1-31.
[50]
Dragicevic-Curic N, Gräfe S, Albrecht V, Fahr A. Topical application of temoporfin-loaded invasomes for photodynamic therapy of subcutaneously implanted tumours in mice: a pilot study. J Photochem Photobiol B 2008; 91(1): 41-50.
[http://dx.doi.org/10.1016/j.jphotobiol.2008.01.009] [PMID: 18316200]
[51]
Dwivedi M, Sharma V, Pathak K. Pilosebaceous targeting by isotretenoin-loaded invasomal gel for the treatment of eosinophilic pustular folliculitis: optimization, efficacy and cellular analysis. Drug Dev Ind Pharm 2017; 43(2): 293-304.
[http://dx.doi.org/10.1080/03639045.2016.1239628] [PMID: 27649797]
[52]
Amnuaikit T, Limsuwan T, Khongkow P, Boonme P. Vesicular carriers containing phenylethyl resorcinol for topical delivery system; liposomes, transfersomes and invasomes. Asian J Pharm Sci 2018; 13(5): 472-84.
[http://dx.doi.org/10.1016/j.ajps.2018.02.004] [PMID: 32104421]
[53]
Feldman S, Careccia RE, Barham KL, Hancox J. Diagnosis and treatment of acne. Am Fam Physician 2004; 69(9): 2123-30.
[PMID: 15152959]
[54]
El-Nabarawi MA, Shamma RN, Farouk F, Nasralla SM. Dapsone-loaded invasomes as a potential treatment of acne: preparation, characterization, and in vivo skin deposition assay. AAPS PharmSciTech 2018; 19(5): 2174-84.
[http://dx.doi.org/10.1208/s12249-018-1025-0] [PMID: 29725903]
[55]
Targhotra M, Gupta M. Development and characterization of effective topical formulation for adapalene-loaded invasomes for acne management. Indian J Pharm Sci Res 2020; 10(1): 1-8.
[56]
Dragicevic-Curic N, Scheglmann D, Albrecht V, Fahr A. Development of different temoporfin-loaded invasomes-novel nanocarriers of temoporfin: characterization, stability and in vitro skin penetration studies. Colloids Surf B Biointerfaces 2009; 70(2): 198-206.
[http://dx.doi.org/10.1016/j.colsurfb.2008.12.030] [PMID: 19188048]
[57]
Prasanthi DK, Lakshmi P. Iontophoretic transdermal delivery of finasteride in vesicular invasomal carriers. Pharm Nanotechnol 2013; 1: 136-50.
[http://dx.doi.org/10.2174/2211738511301020009]
[58]
Qadri GR, Ahad A, Aqil M, Imam SS, Ali A. Invasomes of isradipine for enhanced transdermal delivery against hypertension: formulation, characterization, and in vivo pharmacodynamic study. Artif Cells Nanomed Biotechnol 2017; 45(1): 139-45.
[http://dx.doi.org/10.3109/21691401.2016.1138486] [PMID: 26829018]
[59]
Mura S, Manconi M, Sinico C, Valenti D, Fadda AM. Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil. Int J Pharm 2009; 380(1-2): 72-9.
[http://dx.doi.org/10.1016/j.ijpharm.2009.06.040] [PMID: 19589377]
[60]
Vidya K, Lakshmi P. Cytotoxic effect of transdermal invasomal anastrozole gel on MCF-7 breast cancer cell line. J Appl Pharm Sci 2019; 9: 50-8.
[http://dx.doi.org/10.7324/JAPS.2019.90308]
[61]
Ogiso T, Yamaguchi T, Iwaki M, Tanino T, Miyake Y. Effect of positively and negatively charged liposomes on skin permeation of drugs. J Drug Target 2001; 9(1): 49-59.
[http://dx.doi.org/10.3109/10611860108995632] [PMID: 11378523]
[62]
Sinico C, Manconi M, Peppi M, Lai F, Valenti D, Fadda AM. Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle-skin interaction. J Control Release 2005; 103(1): 123-36.
[http://dx.doi.org/10.1016/j.jconrel.2004.11.020] [PMID: 15710506]
[63]
Chen J, Lu WL, Gu W, Lu SS, Chen ZP, Cai BC. Skin permeation behavior of elastic liposomes: role of formulation ingredients. Expert Opin Drug Deliv 2013; 10(6): 845-56.
[http://dx.doi.org/10.1517/17425247.2013.779252] [PMID: 23550630]
[64]
Rawicz W, Smith BA, McIntosh TJ, Simon SA, Evans E. Elasticity, strength, and water permeability of bilayers that contain raft microdomain-forming lipids. Biophys J 2008; 94(12): 4725-36.
[http://dx.doi.org/10.1529/biophysj.107.121731] [PMID: 18339739]
[65]
van den Bergh BA, Bouwstra JA, Junginger HE, Wertz PW. Elasticity of vesicles affects hairless mouse skin structure and permeability. J Control Release 1999; 62(3): 367-79.
[http://dx.doi.org/10.1016/S0168-3659(99)00168-6] [PMID: 10528074]
[66]
Ntimenou V, Fahr A, Antimisiaris SG. Elastic vesicles for transdermal drug delivery of hydrophilic drugs: a comparison of important physicochemical characteristics of different vesicle types. J Biomed Nanotechnol 2012; 8(4): 613-23.
[http://dx.doi.org/10.1166/jbn.2012.1426] [PMID: 22852471]
[67]
Ashtikar M, Langelüddecke L, Fahr A, Deckert V. Tip-enhanced Raman scattering for tracking of invasomes in the stratum corneum. Biochim Biophys Acta, Gen Subj 2017; 1861(11 Pt A): 2630-9.
[http://dx.doi.org/10.1016/j.bbagen.2017.07.003] [PMID: 28689988]
[68]
Lakshmi P, Mounica V, Manoj KY, Prasanthi D. Preparation and evaluation of curcumin invasomes. Int J Drug Deliv 2014; 6: 113-20.
[69]
Chung G, Oh SB. Eugenol as local anesthetic. In: Natural products: Phytochemistry, botany and metabolism of alkaloids, phenolics and terpenes. Berlin: Springer-Verlag 2013; pp. 4001-15.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy