PRONIOSOMES: A NOVEL VESICULAR CARRIER FOR OCULAR DRUG TARGETING
DOI:
https://doi.org/10.22159/ajpcr.2025v18i7.54552Keywords:
Ocular,, Permeability,, Barriers, Proniosomes,, Nanocarriers.Abstract
The Human body is one of the most fascinating and complex structures present on this earth. It has 5 sensory organs that allow a human to feel, understand and respond according to their surroundings. Amongst these 5 organs, one is the eye. The Eye is considered one of the most important sensory organs of the human body. It helps us in seeing this beautiful and colourful world, present around us. In case any kind of disease or disorder occurs in the eye, then the treatment may take a long time for the condition to return to normal. Ocular drug delivery presents unique challenges in the field of pharmaceutical sciences. This is due to the presence of numerous protective barriers and the complex anatomy of the human eye. Conventional formulations present in the market include eye drops, ointments, creams and gels. These formulations often suffer from various limitations, like low bioavailability, short drug residence time, and even rapid drug elimination. This results in decreased therapeutic efficacy of traditional formulations. To overcome these problems, vesicular systems like proniosomes have emerged in the healthcare field as promising drug delivery carriers in ocular pharmacotherapy. Proniosomes are dry, free-flowing, and non-ionic surfactant-based formulations. Proniosomes convert into niosomes when hydrated. Proniosomes offer numerous advantages in ocular drug delivery. These advantages include enhanced drug stability, increased permeability, and prolonged drug release across the ocular barriers, thus providing increased therapeutic results. This article provides a detailed overview of the anatomy of the human eye, focusing on its structural complexity and barriers which are responsible for alterations in the effective absorption of administered drugs. It even highlights the potential of proniosomal formulations and how they revolutionize ocular pharmacotherapy. Furthermore, this article also elaborates about the various formulation methods of proniosomes, which include the coacervation-phase separation method, slurry method, ether injection method, spray drying method and thin-film hydration method. This review emphasizes the enhanced drug delivery efficiency and the sustained therapeutic effects offered by proniosomal formulations. The future perspectives of proniosomal formulations for research have also been explored in this review while focusing on various innovative strategies that may improve drug targeting and bioavailability. This article mainly aims to serve as a comprehensive source of information about the potential and need for advanced proniosomal formulations in the treatment of Ocular diseases.
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References
Peter M, Panonnummal R. A review on newer ocular drug delivery systems with an emphasis on glaucoma. Adv Pharm Bull. 2021;11(3):399-413. doi: 10.34172/apb.2021.048, PMID 34513615
Durak S, Esmaeili Rad M, Alp Yetisgin A, Eda Sutova H, Kutlu O, Cetinel S, et al. Niosomal drug delivery systems for ocular disease-recent advances and future prospects. Nanomaterials (Basel). 2020 Jun;10(6):1191. doi: 10.3390/nano10061191, PMID 32570885
Kaushik A, Mazumder R, Padhi S, Mazumder A, Budhori R, Manorma et al. Novel approaches in ocular drug delivery-a revolution. Int J Appl Pharm. 2022 May;14:1-11. doi: 10.22159/ijap.2022v14i3.44045
Bremond-Gignac D, Chiambaretta F, Milazzo S. A European perspective on topical ophthalmic antibiotics: Current and evolving options. Ophthalmol Eye Dis. 2011 Jan;3:29-43. doi: 10.4137/OED. S4866, PMID 23861622
Suri R, Beg S, Kohli K. Target strategies for drug delivery bypassing ocular barriers. J Drug Deliv Sci Technol. 2020 Feb;55:101389. doi: 10.1016/j.jddst.2019.101389
Ahmed I. The noncorneal route in ocular drug delivery. In: Mitra A, editor. Ophthalmic Drug Delivery Systems. 2nd ed. United States: CRC Press; 2003. p. 335-63. doi: 10.1201/9780203912072.ch11
Ahmed S, Amin MM, Sayed S. Ocular drug delivery: A comprehensive review. AAPS PharmSciTech. 2023 Feb;24(2):66. doi: 10.1208/ s12249-023-02516-9, PMID 36788150
Bryar PJ, Gu D, Agron S, Eichinger SE. Eye. In: Ernst LM, Ruchelli ED, Carreon CK, Huff DS, editors. Color Atlas of Human Fetal and Neonatal Histology. Cham: Springer International Publishing; 2019. p. 311-23. doi: 10.1007/978-3-030-11425-1_30
Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systemsA shift to the posterior segment. Drug Discov Today. 2008 Feb;13(3- 4):135-43. doi: 10.1016/j.drudis.2007.11.002, PMID 18275911
Pardridge WM. The blood-brain barrier: Bottleneck in brain drug development. NeuroRx. 2005 Jan;2(1):3-14. doi: 10.1602/ neurorx.2.1.3, PMID 15717053
Ghate D, Edelhauser HF. Ocular drug delivery. Expert Opin Drug Deliv. 2006 Mar;3(2):275-87. doi: 10.1517/17425247.3.2.275, PMID 16506953
Kishor RC, Dhewale S, Pawar AA, Vir DK. A review in the vision an novel innovation towards ocular drug delivery system with medication. Int J Creat Res Thoughts. 2025 Jan;13(1):1-2.
Tiwari S, Talreja S. Proniosome: A contemporary extension in drug delivery and specific target. J Interdisip Cycle Res. 2020 Nov;12:126-33.
Wadavkar SD, Khandre RA. Ocular drug delivery system: A review. Int J Creat Res Thoughts. 2022;7(11):9-24.
Ajrin M, Anjum F. Proniosome: A promising approach for vesicular drug delivery. Turk J Pharm Sci. 2022 Aug;19(4):462-75. doi: 10.4274/ tjps.galenos.2021.53533, PMID 36047601
Dubald M, Bourgeois S, Andrieu V, Fessi H. Ophthalmic drug delivery systems for antibiotherapy-a review. Pharmaceutics. 2018 Jan;10(1):10. doi: 10.3390/pharmaceutics10010010, PMID 29342879
Mithra MM, Krishnakumar K, Nair SK. Herbal nanosuspension: In vitro cancer study against different cell lines. Asian J Pharm Clin Res. 2020 Jun;13:25-9. doi: 10.22159/ajpcr.2020.v13i7.37764
Li S, Chen L, Fu Y. Nanotechnology-based ocular drug delivery systems: Recent advances and future prospects. J Nanobiotechnology. 2023 Jul;21(1):232. doi: 10.1186/s12951-023-01992-2, PMID 37480102
Kandpal N, Nainwal N, Ale Y, Semwal Y, Jakhmola V, Padiyar N. Proniosomes: A pro vesicular system in ocular drug delivery. J Adv Biotechnol Exp Ther. 2023;6(3):622. doi: 10.5455/jabet.2023.d154
Hu C, Rhodes DG. Proniosomes: A novel drug carrier preparation. Int J Pharm. 1999 Aug;185(1):23-35. doi: 10.1016/S0378-5173(99)00122-2, PMID 10425362
Scriven LE. Equilibrium bicontinuous structure. Nature. 1976 Sep;263(5573):123-5. doi: 10.1038/263123a0
Gupta DK, Ahad A, Waheed A, Aqil Mohd, Al-Jenoobi FI, Al-Mohizea AM. Bilosomes: A novel platform for drug delivery. In: Systems of Nanovesicular drug Delivery. Netherlands: Elsevier; 2022. p. 293-309. doi: 10.1016/B978-0-323-91864-0.00004-823. Ruiz-Herrera J, Bartnicki-Garcia S, Bracker CE. Dissociation of chitosomes by digitonin into 16 S subunits with chitin synthetase activity. Biochim Biophys Acta. 1980 May;629(2):201-6. doi: 10.1016/0304- 4165(80)90094-X, PMID 6446324
Albash R, Elmahboub Y, Baraka K, Abdellatif MM, Alaa-Eldin AA. Ultra-deformable liposomes containing terpenes (terpesomes) loaded fenticonazole nitrate for treatment of vaginal candidiasis: Box-Behnken design optimization, comparative ex vivo and in vivo studies. Drug Deliv. 2020 Jan;27(1):1514-23. doi: 10.1080/10717544.2020.1837295, PMID 33108907
Abdelkader H, Wu Z, Al-Kassas R, Alany RG. Niosomes and Discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects. Int J Pharm. 2012 Aug;433(1-2):142-8. doi: 10.1016/j.ijpharm.2012.05.011, PMID 22595640
Khan A, Varshney C, Chaudhary T, Singh B. Spanlastics: An innovative formulation strategy in pharmaceutical drug delivery. World J Pharm Res. 2023 Dec;12(20):219-34.
Pawar S, Shashikant D, Shivarkar R. Ethosome: A novel carrier used in transdermal and topical drug delivery. Int J Pharm Res Appl. 2024 May;9(3):2442-552.
Raj A, Dua K, Nair RS, Sarath Chandran C, Alex AT. Transethosome: An ultra-deformable ethanolic vesicle for enhanced transdermal drug delivery. Chem Phys Lipids. 2023 Sep;255:105315. doi: 10.1016/j. chemphyslip.2023.105315, PMID 37356610
Muthangi S, Pallerla P, Nimmagadda S. Transdermal delivery of drugs using transferosomes: A comprehensive review. J Adv Sci Res. 2023 Aug;14(6):30-5. doi: 10.55218/JASR.202314604
Antil D, Sharma R, Bhushan B. Formulation and in vitro characterization of thiocolchicoside proniosomes for oral delivery. Asian J Pharm Clin Res. 2023 Apr;16:114-21. doi: 10.22159/ajpcr.2023.v16i4.46456
Maiti S, Paul S, Mondol R, Ray S, Sa B. Nanovesicular formulation of brimonidine tartrate for the management of glaucoma: In vitro and in vivo evaluation. AAPS PharmSciTech. 2011 Jun;12(2):755-63. doi: 10.1208/s12249-011-9643-9, PMID 21671199
Cholkar K, Dasari SR, Pal D, Mitra AK. Eye: Anatomy, physiology and barriers to drug delivery. In: Ocular Transporters and Receptors. Netherlands: Elsevier; 2013. p. 1-36. doi: 10.1533/9781908818317.1
Eghrari AO, Riazuddin SA, Gottsch JD. Overview of the cornea: Structure, Function, and Development. Prog Mol Biol Transl Sci. 2015;134:7-23. doi: 10.1016/bs.pmbts.2015.04.001, PMID 26310146
Gaudana R, Jwala J, Boddu SH, Mitra AK. Recent perspectives in ocular drug delivery. Pharm Res. 2009 May;26(5):1197-216. doi: 10.1007/ s11095-008-9694-0, PMID 18758924
Rathore KS, Nema RK. An insight into ophthalmic drug delivery system. Int J Pharm Sci Drug Res. 2009 Apr; 1:1-5. doi: 10.25004/ IJPSDR.2009.010101
Ahmad MZ, Mohammed AA, Mokhtar Ibrahim M. Technology overview and drug delivery application of proniosome. Pharm Dev Technol. 2017 Apr;22(3):302-11. doi: 10.3109/10837450.2015.1135344, PMID 26794727
Edsman K, Carlfors J, Petersson R. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. Eur J Pharm Sci. 1998 Apr;6(2):105-12. doi: 10.1016/S0928-0987(97)00075-4, PMID 9795025
Solanki A, Parikh J, Parikh R. Solanki proniosomes. Iran J Pharm Res. 2008 Nov;7(4):237-46. doi: 10.22037/ijpr.2010.772
Abdelbary AA, Abd-Elsalam WH, Al-Mahallawi AM. Fabrication of novel ultradeformable bilosomes for enhanced ocular delivery of terconazole: In vitro characterization, ex vivo permeation and in vivo safety assessment. Int J Pharm. 2016 Nov;513(1-2):688-96. doi: 10.1016/j.ijpharm.2016.10.006, PMID 27717916
Mohsen AM, Salama A, Kassem AA. Development of acetazolamide loaded bilosomes for improved ocular delivery: Preparation, characterization and in vivo evaluation. J Drug Deliv Sci Technol. 2020 Oct;59:101910. doi: 10.1016/j.jddst.2020.101910
Janga KY, Tatke A, Balguri SP, Lamichanne SP, Ibrahim MM, Maria DN, et al. Ion-sensitive in situ hydrogels of natamycin bilosomes for enhanced and prolonged ocular pharmacotherapy: In vitro permeability, cytotoxicity and in vivo evaluation. Artif Cells Nanomed Biotechnol. 2018 Oct;46:1039-50. doi: 10.1080/21691401.2018.1443117, PMID 29475386
Teba HE, Khalil IA, El Sorogy HM. Novel cubosome based system for ocular delivery of acetazolamide. Drug Deliv. 2021 Jan;28(1):2177-86. doi: 10.1080/10717544.2021.1989090, PMID 34662264
Said M, Aboelwafa AA, Elshafeey AH, Elsayed I. Central composite optimization of ocular mucoadhesive cubosomes for enhanced bioavailability and controlled delivery of voriconazole. J Drug Deliv Sci Technol. 2021 Feb;61:102075. doi: 10.1016/j.jddst.2020.102075
Bessone CD, Akhlaghi SP, Tártara LI, Quinteros DA, Loh W, Allemandi DA. Latanoprost-loaded phytantriol cubosomes for the treatment of glaucoma. Eur J Pharm Sci. 2021 May;160:105748. doi: 10.1016/j.ejps.2021.105748, PMID 33567324
Ameeduzzafar, Alruwaili NK, Imam SS, Alotaibi NH, Alhakamy NA, Alharbi KS, et al. Formulation of chitosan polymeric vesicles of ciprofloxacin for ocular delivery: Box-Behnken optimization, in vitro characterization, HET-CAM irritation, and antimicrobial assessment. AAPS PharmSciTech. 2020 Jul;21(5):167. doi: 10.1208/s12249-020- 01699-9, PMID 32504176
Zafar A, Alruwaili NK, Imam SS, Alsaidan OA, Alharbi KS, Yasir M, et al. Formulation of carteolol chitosomes for ocular delivery: Formulation optimization, ex-vivo permeation, and ocular toxicity examination. Cutan Ocul Toxicol. 2021 Oct;40(4):338-49. doi: 10.1080/15569527.2021.1958225, PMID 34340615
Aziz D, Mohamed S, Tayel S, Makhlouf A. Flexosomes as a promising nanoplatform for enhancing tolnaftate ocular delivery: Formulation, in vitro characterization, statistical optimization, ex vivo and microbial in vivo studies. Int J Pharm. 2023 Nov;646:123471. doi: 10.1016/j. ijpharm.2023.123471, PMID 37793467
Omran S, Elnaggar YS, Abdallah OY. Controlled release, chitosan-tethered luteolin phytocubosomes; Formulation optimization to in-vivo antiglaucoma and anti-inflammatory ocular evaluation. Int J Biol Macromol. 2024 Jan;254(3):127930. doi: 10.1016/j. ijbiomac.2023.127930, PMID 37944733
Mahboobian MM, Mohammadi M, Mansouri Z. Development of thermosensitive in situ gel nanoemulsions for ocular delivery of acyclovir. J Drug Deliv Sci Technol. 2020 Feb;55:101400. doi: 10.1016/j.jddst.2019.101400
Tayel SA, El-Nabarawi MA, Tadros MI, Abd-Elsalam WH. Promising ion-sensitive in situ ocular nanoemulsion gels of terbinafine hydrochloride: Design, in vitro characterization and in vivo estimation of the ocular irritation and drug pharmacokinetics in the aqueous humor of rabbits. Int J Pharm. 2013 Feb;443(1-2):293-305. doi: 10.1016/j. ijpharm.2012.12.049, PMID 23333217
Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G. Eudragit RS100® nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci. 2002 Jul;16(1-2):53-61. doi: 10.1016/S0928-0987(02)00057-X, PMID 12113891
Wang J, Li B, Huang D, Norat P, Grannonico M, Cooper RC, et al. Nano-in-Nano dendrimer gel particles for efficient topical delivery of antiglaucoma drugs into the eye. Chem Eng J. 2021 Dec;425:130498. doi: 10.1016/j.cej.2021.130498, PMID 34121919
Parekh HS, Marano RJ, Rakoczy EP, Blanchfield J, Toth I. Synthesis of a library of polycationic lipid core dendrimers and their evaluation in the delivery of an oligonucleotide with hVEGF inhibition. Bioorg Med Chem. 2006 Jul;14(14):4775-80. doi: 10.1016/j.bmc.2006.03.029, PMID 16603365
Başaran E, Demirel M, Sırmagül B, Yazan Y. Cyclosporine-A incorporated cationic solid lipid nanoparticles for ocular delivery. J Microencapsul. 2010 Jan;27(1):37-47. doi: 10.3109/02652040902846883, PMID 19545226
Ramadan AA, Eladawy SA, El-Enin AS, Hussein ZM. Development and investigation of timolol maleate niosomal formulations for the treatment of glaucoma. J Pharm Investig. 2020 Jan;50(1):59-70. doi: 10.1007/s40005-019-00427-1
Khalil RM, Abdelbary GA, Basha M, Awad GE, El-Hashemy HA. Enhancement of lomefloxacin Hcl ocular efficacy via niosomal encapsulation: In vitro characterization and in vivo evaluation. J Liposome Res. 2017 Oct;27(4):312-23. doi: 10.1080/08982104.2016.1191022, PMID 27241274
Hashemi Dehaghi M, Haeri A, Keshvari H, Abbasian Z, Dadashzadeh S. Dorzolamide loaded niosomal vesicles: Comparison of passive and remote loading methods. Iran J Pharm Res. 2017;16(2):413-22. PMID 28979296
Verma A, Sharma G, Jain A, Tiwari A, Saraf S, Panda PK, et al. Systematic optimization of cationic surface engineered mucoadhesive vesicles employing Design of experiment (DoE): A preclinical investigation. Int J Biol Macromol. 2019 Jul;133:1142-55. doi: 10.1016/j.ijbiomac.2019.04.118, PMID 31004631
Liu Y, Wang Y, Yang J, Zhang H, Gan L. Cationized hyaluronic acid coated spanlastics for cyclosporine a ocular delivery: Prolonged ocular retention, enhanced corneal permeation and improved tear production. Int J Pharm. 2019 Jun;565:133-42. doi: 10.1016/j.ijpharm.2019.05.018, PMID 31075435
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