Formulation, Statistical Optimization and In Vitro ‎Evaluation of Transdermal Anastrozole Nanospanlastic

Authors

  • Laila A. Alwan Alalkawy Ministry of Health ,Diyala Health Department, Baghdad, Iraq.
  • Shaimaa Nazar Abd Alhammid Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.31351/vol34iss4pp197-214

Keywords:

Anastrozole, Edge activator, Nanospanlastic, Surface randomized design, Transdermal.

Abstract

In postmenopausal women, anastrozole reduces estrogen levels, which may inhibit the development of certain breast cancers that need estrogen to increase in the body. The limitations of anastrozole are the first-pass action, limited aqueous solubility, and gastrointestinal issues. Additionally, improving skin permeability, controlling drug release, and shielding sensitive molecules from deterioration are just a few of the uses for nanoparticles that are gaining popularity. Spanlastics are elastic, malleable nanovesicles based on surfactants. They comprise an edge activator (EA) and a nonionic surfactant. In this study, anastrozole nanospanlastic (Ana-SPLs) was created to improve patient compliance and control anastrozole transdermal distribution as an alternative to the oral route. Therefore, the study aimed to develop a formulation that could get around these problems by using the advantages of the transdermal administration route and nanotechnology concepts. Minimized sizes with higher absolute zeta potential Ana-SPLs were formulated using a response-surface randomized User-Defind method. In addition to one category component that addresses the kind of EA, two numerical variables were examined: Span 60 to EA ratio (w/w) and sonication duration (min). Zeta potential (mV) and particle size (nm) were investigated as responses. A mathematical optimization technique was used to forecast the optimal variable values. With a sonication period of 5 minutes, the optimized formulation with a Span 60: SDC ratio of 9:1 w/w revealed particle dimensions of 128 nm with a zeta potential of -32 mV. Formula (F2) was seen using transmission electron microscopy to have a homogeneous, spherical shape. Because of its tiny particle size, high entrapment efficiency percentage (80.2 ± 4.3%), and 12-hour release pattern, formula (F2) was selected for further analysis. The compatibility study did not consider the interaction of Ana with other components. The previously described findings suggest spanlastics may be potentially effective drug carriers for transdermal medication administration.

How to Cite

1.
Alalkawy LAA, Shaimaa Nazar Abd Alhammid. Formulation, Statistical Optimization and In Vitro ‎Evaluation of Transdermal Anastrozole Nanospanlastic. Iraqi Journal of Pharmaceutical Sciences [Internet]. 2025 Dec. 20 [cited 2025 Dec. 22];34(4):197-214. Available from: https://www.bijps.uobaghdad.edu.iq/index.php/bijps/article/view/3803

Publication Dates

Received

2024-05-23

Revised

2024-08-15

Accepted

2024-11-12

Published Online First

2025-12-20

References

Stebbing J, Ngan S. Breast cancer (metastatic). BMJ Clinical Evidence. 2010;2010.

Hortobagyi GN, Buzdar AU. Anastrozole (Arimidex®), a new aromatase inhibitor for advanced breast cancer: mechanism of action and role in management. Cancer investigation. 1998 Jan 1;16(6):385-90.

Heer E, Harper A, Escandor N, Sung H, McCormack V, Fidler-Benaoudia MM. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. The Lancet Global Health. 2020 Aug 1;8(8):e1027-37.

Coughlin SS. Epidemiology of breast cancer in women. Breast Cancer Metastasis and Drug Resistance: Challenges and Progress. 2019:9-29.

Kunstič TT, Debeljak N, Tacer KF. Heterogeneity in hormone-dependent breast cancer and therapy: Steroid hormones, HER2, melanoma antigens, and cannabinoid receptors. Advances in Cancer Biology-Metastasis. 2023 Jul 1; 7:100086.

Horwitz KB, Sartorius CA. Ninety years of progesterone: progesterone and progesterone receptors in breast cancer: past, present, future. Journal of Molecular Endocrinology. 2020 Jul 1;65(1):T49-63.

Allison KH, Hammond ME, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM. Estrogen and progesterone receptor testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists guideline update. Archives of pathology & laboratory medicine. 2020 May 1;144(5):545-63.

Refaat B, Aslam A, Idris S, Almalki AH, Alkhaldi MY, Asiri HA, Almaimani RA, Mujalli A, Minshawi F, Alamri SA, AlHussain MI. Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness. Frontiers in Endocrinology. 2023 May 3; 14:1187259.

Iacopetta D, Ceramella J, Baldino N, Sinicropi MS, Catalano A. Targeting breast cancer: An overlook on current strategies. International Journal of Molecular Sciences. 2023 Feb 11;24(4):3643.

Navaei NM, Navaei NM. Unlocking the potential of aromatase inhibitors: recent advances in drug design, synthesis, docking activity, and in vitro bioactivity evaluations. Synthesis and Sintering. 2023 Dec 2;3(4):234-40.

Emond R, Griffiths JI, Grolmusz VK, Nath A, Chen J, Medina EF, Sousa RS, Synold T, Adler FR, Bild AH. Cell facilitation promotes growth and survival under drug pressure in breast cancer. Nature Communications. 2023 Jun 29;14(1):3851.

Kasar RR, Ahir KN. Current and emerging biomarkers in breast cancer: A review. World Journal of Biology Pharmacy and Health Sciences. 2024;17(3):001-25.

In: Carrell DT, Pastuszak AW, Hotaling JM, editors. Men's Reproductive and Sexual Health Throughout the Lifespan: An Integrated Approach to Fertility, Sexual Function, and Vitality. Cambridge: Cambridge University Press; 2023. p. 264–8

Najm A, Niculescu AG, Grumezescu AM, Beuran M. Emerging Therapeutic Strategies in Sarcopenia: An Updated Review on Pathogenesis and Treatment Advances. International Journal of Molecular Sciences. 2024 Apr 12;25(8):4300.

Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. Journal of Clinical Oncology. 2003 Sep 1;21(17):3357-65.

Huppert LA, Gumusay O, Idossa D, Rugo HS. Systemic therapy for hormone receptor‐positive/human epidermal growth factor receptor 2‐negative early stage and metastatic breast cancer. CA: A Cancer Journal for Clinicians. 2023 Sep;73(5):480-515.

Alhammid SN, Kassab HJ, Hussein LS, Haiss MA. Spanlastics Nanovesicles: An Emerging and Innovative Approach for Drug Delivery. Maren Journal for Medical Sciences. 2023;2(2):9.

Alwan LA, Abd Alhammid SN. A modern method for the delivery of nano vesicular drugs, spanlastics. IAR J Pharm 2023, 4(6): 01-10

Gad S, Hanna P, Ibrahim H, Mortagi Y. Surfactants' Role in Nanovesicles Drug Delivery System. Records of Pharmaceutical and Biomedical Sciences. 2023 Jan 1;7(3):140-9.

Ali AA, Hassan AH, Eissa EM, Aboud HM. Response surface optimization of ultra-elastic nanovesicles loaded with deflazacort tailored for transdermal delivery: Accentuated bioavailability and anti-inflammatory efficacy. International Journal of Nanomedicine. 2021 Jan 25:591-607.

Saini H, Rapolu Y, Razdan K, Nirmala, Sinha VR. Spanlastics: a novel elastic drug delivery system with potential applications via multifarious routes of administration. Journal of Drug Targeting. 2023 Nov 26;31(10):999-1012.

Muzammil S, Mazhar A, Yeni DK, Andleeb R, Ashraf A, Shehzad MI, Zafar N, Mazhar M. Nanospanlastic as a promising nanovesicle for drug delivery 2022 Jan 1 (pp. 337-352). Academic Press.

Ansari MD, Saifi Z, Pandit J, Khan I, Solanki P, Sultana Y, Aqil M. Spanlastics a novel nano vesicular carrier: its potential application and emerging trends in therapeutic delivery. AAPS PharmSciTech. 2022 Apr 11;23(4):112.

Al-Mahallawi AM, Khowessah OM, Shoukri RA. Enhanced non-invasive trans-tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: Fabrication, in-vitro characterization, and comparative ex-vivo permeation studies. International journal of pharmaceutics. 2017 Apr 30;522(1-2):157-64.

Abdelbari MA, El-Mancy SS, Elshafeey AH, Abdelbary AA. Implementing spanlastics for improving the ocular delivery of clotrimazole: in vitro characterization, ex vivo permeability, microbiological assessment and in vivo safety study. International Journal of Nanomedicine. 2021 Sep 10:6249-61.

Elsherif NI, Shamma RN, Abdelbary G. Terbinafine hydrochloride trans-ungual delivery via nano vesicular systems: in vitro characterization and ex vivo evaluation. AAPS PharmsciTech. 2017 Feb; 18:551-62.

Placha D, Jampilek J. Chronic inflammatory diseases, anti-inflammatory agents and their delivery nanosystems. Pharmaceutics. 2021 Jan 6;13(1):64.

Mazyed EA, Helal DA, Elkhoudary MM, Abd Elhameed AG, Yasser M. Formulation and optimization of nanospanlastics for improving the bioavailability of green tea epigallocatechin gallate. Pharmaceuticals. 2021 Jan 15;14(1):68.

Fahmy AM, El-Setouhy DA, Habib BA, Tayel SA. Enhancement of transdermal delivery of haloperidol via spanlastic dispersions: entrapment efficiency vs particle size. AAPS PharmsciTech. 2019 Apr; 20:1-3.

Ibrahim SS, Abd-Allah H. Spanlastic nanovesicles for enhanced ocular delivery of vanillic acid: design, in vitro characterization, and in vivo anti-inflammatory evaluation. International Journal of Pharmaceutics. 2022 Sep 25; 625:122068.

Badria F, Mazyed E. Formulation of nanospanlastics as a promising approach for‎ improving the topical delivery of a natural leukotriene inhibitor (3-‎ acetyl-11-keto-β-boswellic acid): statistical optimization, in vitro‎ characterization, and ex vivo permeation study. Drug design, development and therapy. 2020 Sep 15:3697-721.

Ibrahim MM, Basalious EB, El-Nabarawi MA, Makhlouf AI, Sayyed ME, Ibrahim IT. Nose to brain delivery of mirtazapine via lipid nanocapsules: Preparation, statistical optimization, radiolabeling, in vivo biodistribution and pharmacokinetic study. Drug Delivery and Translational Research. 2024 Feb 20:1-9.

Mekkawy AI, Eleraky NE, Soliman GM, Elnaggar MG, Elnaggar MG. Combinatorial therapy of letrozole-and quercetin-loaded spanlastics for enhanced cytotoxicity against MCF-7 breast cancer cells. Pharmaceutics. 2022 Aug 18;14(8):1727.

Zaki RM, Ibrahim MA, Alshora DH, El Ela AE. Formulation and evaluation of transdermal gel containing tacrolimus-loaded spanlastics: in vitro, ex vivo and in vivo studies. Polymers. 2022 Apr 9;14(8):1528.

Drais HK. Transdermal Delivery of Lornoxicam Hybrid Nanogel: Design, Preparation, Characterization, and In-Vitro Diffusion Evaluation. Iraqi Journal of Industrial Research. 2023 Oct 20;10(2):98-104.

Hashim AA, Rajab NA. Anastrozole loaded nanostructured lipid carriers: preparation and evaluation. Iraqi Journal of Pharmaceutical Sciences. 2021 Dec 11;30(2):185-95.

Radhi A, Ali WK, Al-Saedi F. Preparation and in vitro evaluation of synthetic high-density lipoproteins as parenteral drug delivery system for tamoxifen citrate. Iraqi Journal of Pharmaceutical Sciences. 2023 Dec 30;32(3):105-17.

Albassam NY, Kassab HJ. Diacerein loaded novasome for transdermal delivery: Preparation, in-vitro characterization and factors affecting formulation. Iraqi Journal of Pharmaceutical Sciences. 2023 Nov 3;32(Suppl.):214-24.

Abdullah TM, Khalid KA. Topical Propranolol Hydrochloride Nanoemulsion: A Promising Approach Drug Delivery for Infantile Hemangiomas. Iraqi Journal of Pharmaceutical Sciences. 2023 Nov 4;32(Suppl.):300-15.

Salih OS, Al-Akkam EJ. Preparation, in-vitro, and ex-vivo evaluation of ondansetron-loaded invasomes for transdermal delivery. IJPS. 2023 Dec 30;32(3):71–84. https://doi.org/10. 31351/ vol32iss3pp71-84

Pereira-Silva M, Jarak I, Alvarez-Lorenzo C, Concheiro A, Santos AC, Veiga F, Figueiras A. Micelleplexes as nucleic acid delivery systems for cancer-targeted therapies. Journal of controlled release. 2020 Jul 10; 323:442-62.

Sultan MH, Moni SS, Madkhali OA, Bakkari MA, Alshahrani S, Alqahtani SS, Alhakamy NA, Mohan S, Ghazwani M, Bukhary HA, Almoshari Y. Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer. Scientific reports. 2022 Jan 10;12(1):468.

Abbas H, El-Feky YA, Al-Sawahli MM, El-Deeb NM, El-Nassan HB, Zewail M. Development and optimization of curcumin analogue nano-bilosomes using 21.31 full factorial design for anti-tumour profiles improvement in human hepatocellular carcinoma: In-vitro evaluation, in-vivo safety assay. Drug Delivery. 2022 Dec 31;29(1):714-27.

Haroon H.B., Mukherjee D., Anbu J., Teja B.V. Thiolated Chitosan-Centella Asiatica Nanocomposite: A Potential Brain Targeting Strategy Through Nasal Route. AAPS PharmSciTech. 2021; 22:251.

Nguyen T.T.L., Maeng H.J. Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery. Pharmaceutics. 2022; 14:572. doi 10.3390/pharmaceutics14030572.

Saad A, Sabri L. Study the Variables Affecting Formulation of Ethylcellulose-based Microsponges Loaded with Clobetasol. Iraqi Journal of Pharmaceutical Sciences. 2023 Nov 3;32(Suppl.):225-34.

Badr-Eldin SM, Aldawsari HM, Alhakamy NA, Fahmy UA, Ahmed OA, Neamatallah T, Tima S, Almaghrabi RH, Alkudsi FM, Alamoudi AA, Alzahrani AA. Merging experimental design and nanotechnology for developing optimized simvastatin spanlastics: A promising combined strategy for augmenting the suppression of various human cancer cells. Pharmaceutics. 2022 May 9;14(5):1024.

Alhagiesa AW, Ghareeb MM. The Formulation and Characterization of Nimodipine Nanoparticles to enhance solubility and dissolution rate. Iraqi Journal of Pharmaceutical Sciences. 2021 Dec 11;30(2):143-52.

Nowroozi F, Almasi A, Javidi J, Haeri A, Dadashzadeh S. Effect of surfactant type, cholesterol content and various downsizing methods on the particle size of niosomes. Iranian journal of pharmaceutical Research. 2018;17(Suppl2):1.

Nourzadeh Z, Anarjan N, Ebrahimzadeh Rajaei G, Jafarizadeh-Malmiri H. Preparation and characterization of vitamin D microemulsions using two-component surface-active stabilizer system. Zeitschrift für Physikalische Chemie. 2022 Feb 23;236(2):257-74.

Abdelrahman F.E., Elsayed I., Gad M.K., Elshafeey A.H., Mohamed M.I. Response Surface Optimization, Ex Vivo and In Vivo Investigation of Nasal Spanlastics for Bioavailability Enhancement and Brain Targeting of Risperidone. 2017; 530:1–11.

Alaaeldin E, Mostafa M, Mansour HF, Soliman GM. Spanlastics as an efficient delivery system for enhancing thymoquinone anticancer efficacy: Fabrication and cytotoxic studies against breast cancer cell lines. Journal of Drug Delivery Science and Technology. 2021 Oct 1; 65:102725.

Ansari MD, Solanki P, Pandit J, Jahan RN, Aqil M, Sultana Y. Fabrication and optimization of raloxifene loaded spanlastics vesicle for transdermal delivery. Journal of Drug Delivery Science and Technology. 2022 Feb 1; 68:103102.

Basalious EB, Shawky N, Badr-Eldin SM. SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: development and optimization. Int J Pharm. 2010;391 (1–2):203–211.

Saini H, Rapolu Y, Razdan K, Nirmala, Sinha VR. Spanlastics: a novel elastic drug delivery system with potential applications via multifarious routes of administration. Journal of Drug Targeting. 2023 Nov 26;31(10):999-1012.

Ruckmani K, Jayakar B, Ghosal SK. Nonionic surfactant vesicles (niosomes) of cytarabine hydrochloride for effective treatment of leukaemias: encapsulation, storage, and in vitro release. Drug Dev Ind Pharm. 2000; 26(2):217–222.

Souto EB, Fangueiro JF, Fernandes AR, Cano A, Sanchez-Lopez E, Garcia ML, Severino P, Paganelli MO, Chaud MV, Silva AM. Physicochemical and biopharmaceutical aspects influencing skin permeation and role of SLN and NLC for skin drug delivery. Heliyon. 2022 Feb 11.

Regenthal R, Voskanian M, Baumann F, Teichert J, Brätter C, Aigner A, Abraham G. Pharmacokinetic evaluation of a transdermal anastrozole-in-adhesive formulation. Drug Design, Development and Therapy. 2018 Nov 1:3653-64.

Salih O, Muhammed E. Preparation, evaluation, and histopathological studies of ondansetron-loaded invasomes transdermal gel. J Res Pharm. 2024;28(1)(28(1)):289–303.

Jaafer H, Al-Kinani KK. Formulation and Evaluation of Idebenone Microemulsion as a Potential Approach for the Transmucosal Drug Delivery Systems. Iraqi Journal of Pharmaceutical Sciences. 2024 Mar 26;33(1):79-88.

Mazyed EA, Abdelaziz AE. Fabrication of transgelosomes for enhancing the ocular delivery of acetazolamide: statistical optimization, in vitro characterization, and in vivo study. Pharmaceutics. 2020;12(5):465.

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2025-12-20

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Vol. 34 No. 4 (2025): 2025

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