The Potential for Enhanced Systemic Delivery of Nimodipine Loaded Polymeric Nanoparticles via Bilayer Dissolving Microneedles
DOI:
https://doi.org/10.31351/vol35iss1pp9-21Abstract
Nimodipine (NID) is used for the prevention of ruptured intracranial aneurysms and subarachnoid haemorrhage (SAH). The objective of study using the benefits of a combined approach of polymeric nanoparticles and microneedles to fabricate NID as polymeric nanoparticles (NID-NPs) loaded in a bilayer dissolving microneedle (bDMNs) patch to enhance the delivery of drugs through skin layers as a promising noninvasive and painless delivery system, improving poor solubility and lower oral bioavailability (5–10%) owing to first-pass metabolism, which leads to frequent dosing, inconsistent clinical responses, and poor patient compliance. The NID-NPs formula was fabricated with a (1:8) drug to polymer, Soluplus®, w/w ratio and 0.25% polyvinylpyrrolidone K15 (PVPK15) using nanoprecipitation technique. Formulas were characterized by measuring particle size (PS), polydisperse index (PDI), and entrapment efficiency (%EE). It exhibits a PS (81.78 nm) and PDI (0.046), zeta potential (-18.96 mV), and aspherical shape examined by transmission electron microscopy (TEM) with improved NID release. Moreover, the formula was designed as bilayer dissolved microneedles (bDMNs) using micromolding technique in polydimethylsiloxane (PDMS) molds. Eight microneedle (MN1-MN8) patches of polymers such as hyaluronic acid (HA), polyvinylpyrrolidone (PAPK30), polyvinyl alcohol (PVA), carboxymethylcellulose (CMC), and Pullulan (Pu) employ two plasticizers, glycerin (Gly) and polyethylene glycol 400 (PEG). The optimised formula MN2 with 10% PVA and 5% glycerin as amatrix was evaluated by measuring drug content, % moisture absorbance (%MA), weight variation, surface pH, and maximum mechanical needle strength for all MNs. Ex-vivo permeation study displayed that 80% of NID permeated in less than 2hr with a lag time of 2-3min. Insertion and mechanical studies show high resistance. Morphological study by field emission scanning electron microscopy (FE-SEM) was studied before and after the insertion into the skin, which displays sharp, strong, and uniform MNs. As a result, NP-bDMNs achieved an improvement in both solubility and drug release for transdermal drug delivery, reduced dose frequency, fewer side effects, and improved patient compliance.
How to Cite
Publication Dates
Received
Revised
Accepted
Published Online First
References
- Phuna ZX, Panda BP, Aregowda SH, Madhavan P. Recent development in nanocrystal-based drug delivery for neurodegenerative diseases: Scope, challenges, current and future prospects. Journal of Drug Delivery Science and Technology. 2022; 68:102921.
- Guidance D. Guidance for industry considering whether an FDA-regulated product involves the application of nanotechnology. Biotechnol Law Rep. 2011;30(5):613-6.
- Yarlagadda T, Sharma S, Yarlagadda PK, Sharma J. Recent developments in the Field of nanotechnology for development of medical implants. Procedia Manufacturing. 2019; 30:544-51.
- Khan S, Minhas MU, Tekko IA, Donnelly RF, Thakur RRS. Evaluation of microneedles-assisted in situ depot forming poloxamer gels for sustained transdermal drug delivery. Drug delivery and translational research. 2019; 9:764-82.
- Sivaraman A, Banga AK. Novel in situ forming hydrogel microneedles for transdermal drug delivery. Drug delivery and translational research. 2017; 7:16-26.
- Fonseca DF, Vilela C, Pinto RJ, Bastos V, Oliveira H, Catarino J, et al. Bacterial nanocellulose-hyaluronic acid microneedle patches for skin applications: In vitro and in vivo evaluation. Materials Science and Engineering: C. 2021; 118:111350.
- McCrudden MT, Alkilani AZ, McCrudden CM, McAlister E, McCarthy HO, Woolfson AD, et al. Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs. Journal of Controlled Release. 2014; 180:71-80.
- Waghule T, Singhvi G, Dubey SK, Pandey MM, Gupta G, Singh M, et al. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & pharmacotherapy. 2019; 109:1249-58.
- González-Vázquez P, Larrañeta E, McCrudden MT, Jarrahian C, Rein-Weston A, Quintanar-Solares M, et al. Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis. Journal of Controlled Release. 2017; 265:30-40.
- Zhao Y, Xin T, Ye T, Yang X, Pan W. Solid dispersion in the development of a nimodipine delayed-release tablet formulation. Asian journal of pharmaceutical sciences. 2014;9(1):35-41.
- Soliman GM, Sharma R, Choi AO, Varshney SK, Winnik FM, Kakkar AK, et al. Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers. Biomaterials. 2010;31(32):8382-92.
- Huang S, Huang Z, Fu Z, Shi Y, Dai Q, Tang S, et al. A novel drug delivery carrier comprised of nimodipine drug solution and a nanoemulsion: preparation, characterization, in vitro, and in vivo studies. International journal of nanomedicine. 2020:1161-72.
- Alwan LA, Al-Akkam E. Formulation and Evaluation of Transdermal Dissolved Microneedles Patches for Meloxicam. International Journal of Drug Delivery Technology. 2021;11:656-62.
- Al-Omar MA. Nimodipine: Physical profile. Profiles of Drug Substances, Excipients and Related Methodology. 31: Elsevier; 2005. p. 337-54.
- AlSheyyab RY, Obaidat RM, Altall YR, Abuhuwaij RT, Ghanma RR, Ailabouni AS, et al. Solubility enhancement of nimodipine through preparation of Soluplus® dispersions. Journal of Applied Pharmaceutical Science. 2019;9(9):030-7.
- Lahoti S, Toshniwal S. Development, and validation of UV spectrophotometric method of nimodipine in bulk and tablet formulation. Asian Journal of Biomedical and Pharmaceutical Sciences. 2012;2(7).
- Shelake S, Patil S, Patil S, Sangave P. Formulation, and evaluation of fenofibrate-loaded nanoparticles by precipitation method. Indian J Pharm Sci. 2018;80(3):420-7.
- Rashid AM, Abd-Alhammid SN. Formulation and characterization of itraconazole as nanosuspension dosage form for enhancement of solubility. Iraqi Journal of Pharmaceutical Sciences. 2019;28(2):124-33.
- Alzalzalee R, Kassab H. Factors affecting the preparation of Cilnidipine nanoparticles. Iraqi Journal of Pharmaceutical Sciences. 2023;32(Suppl.):235-43.
- Bohrey S, Chourasiya V, Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Convergence. 2016;3(1):1-7.
- Zhu S, Zhang B, Wang Y, He Y, Qian G, Deng L, et al. A bilayer microneedle for therapeutic peptide delivery towards the treatment of diabetes in db/db mice. Journal of drug delivery science and technology. 2021;62:102336.
- Toma NM, Abdulrasool AA. Formulation and Evaluation of Montelukast Sodium Nanoparticles for Transdermal Delivery. International Journal of Drug Delivery Technology. 2021;11(2):530-538.
- Ling M-H, Chen M-C. Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats. Acta biomaterialia. 2013;9(11):8952-61.
- Mir M, Permana AD, Ahmed N, Khan GM, ur Rehman A, Donnelly RF. Enhancement in site-specific delivery of carvacrol for potential treatment of infected wounds using infection responsive nanoparticles loaded into dissolving microneedles: A proof of concept study. European Journal of Pharmaceutics and Biopharmaceutics. 2020;147:57-68.
- Noor AH, Ghareeb MM. Formulation and evaluation of ondansetron HCl nanoparticles for transdermal delivery. Iraqi Journal of Pharmaceutical Sciences. 2020;29(2):70-9.
- Guan T, Miao Y, Xu L, Yang S, Wang J, He H, et al. Injectable nimodipine-loaded nanoliposomes: preparation, lyophilization and characteristics. International journal of pharmaceutics. 2011;410(1-2):180-7.
- Teng Z, Yu M, Ding Y, Zhang H, Shen Y, Jiang M, et al. Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability. International Journal of Nanomedicine. 2019:119-33.
- Minuti AE, Labusca L, Herea D-D, Stoian G, Chiriac H, Lupu N. A Simple Protocol for Sample Preparation for Scanning Electron Microscopic Imaging Allows Quick Screening of Nanomaterials Adhering to Cell Surface. International Journal of Molecular Sciences. 2022;24(1):430.
- Sadeq ZA. Microneedle Array Patches: Characterization and in-vitro Evaluation. Iraqi Journal of Pharmaceutical Sciences. 2021;30(1):66-75.
- Noor A, Ghareeb M. Transdermal dissolvable microneedle-mediated delivery of controlled release ondansetron hydrogen chloride nanoparticles. IJDDT. 2021;11:858-63.
- Alkhiro AR, Ghareeb MM. Formulation and Evaluation of Iornoxicam as Dissolving Microneedle Patch. Iraqi J Pharm Sci. 2020;29:184-94.1.
- Kumar SS, Behury B, Sachinkumar P. Formulation and evaluation of transdermal patch of Stavudine. Dhaka University journal of Pharmaceutical sciences. 2013;12(1):63-9.
- Wang QL, Ren JW, Chen BZ, Jin X, Zhang CY, Guo XD. Effect of humidity on mechanical properties of dissolving microneedles for transdermal drug delivery. Journal of industrial and engineering chemistry. 2018; 59:251-8.
- Lutton RE, Moore J, Larrañeta E, Ligett S, Woolfson AD, Donnelly RF. Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation. Drug delivery and translational research. 2015; 5:313-31.
- Jiang X, Chen P, Niu W, Fang R, Chen H, An Y, et al. Preparation and evaluation of dissolving tofacitinib microneedles for effective management of rheumatoid arthritis. European Journal of Pharmaceutical Sciences. 2023; 188:106518.
- Ripolin A, Quinn J, Larrañeta E, Vicente-Perez EM, Barry J, Donnelly RF. Successful application of large microneedle patches by human volunteers. International journal of pharmaceutics. 2017;521(1-2):92-101.
- Abdullah T, Al-Kinani K. Propranolol nanoemulgel: Preparation, in-vitro and ex-vivo characterization for a potential local hemangioma therapy. Pharmacia. 2024; 71:1-12.
- Neamah MJ, Al-Akkam EJM. Preparation and characterization of vemurafenib microemulsion based hydrogel using surface active ionic liquid. Pharmacia. 2024; 71:1-9.
- Hamzah ML, Kassab HJ. Formulation and Characterization of Intranasal Drug Delivery of Frovatriptan-Loaded Binary Ethosomes Gel for Brain Targeting. Nanotechnology, Science and Applications. 2024:1-19. Fan C, Li X, Zhou Y, Zhao
- Y, Ma S, Li W, et al. Enhanced topical delivery of tetrandrine by ethosomes for treatment of arthritis. BioMed research international. 2013;2013.
- Jakubowska E, Milanowski B, Lulek J. A systematic approach to the development of cilostazol nanosuspension by liquid antisolvent precipitation (LASP) and its combination with ultrasound. International Journal of Molecular Sciences. 2021;22(22):12406.
- Vora LK, Courtenay AJ, Tekko IA, Larrañeta E, Donnelly RF. Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules. International journal of biological macromolecules. 2020; 146:290-8.
- Cárcamo-Martínez Á, Anjani QK, Permana AD, Cordeiro AS, Larrañeta E, Donnelly RF. Coated polymeric needles for rapid and deep intradermal delivery. International Journal of Pharmaceutics. 2020; 2:100048.
- Migdadi EM, Courtenay AJ, Tekko IA, McCrudden MT, Kearney M-C, McAlister E, et al. Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride. Journal of controlled release. 2018; 285:142-51.
Downloads
Published
License
Copyright (c) 2026 Iraqi Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
