Studies on Risperidone Loaded β-Cyclodextrin Nanosponges for Managing Altered Mental Status and Delirium in Cancer Patients

• Mohd Muqtader Ahmed

  University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur Dt, AP-522510, India

• P. Ravi

  University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur Dt, AP-522510, India

• K.E. Pravallika

  University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur Dt, AP-522510, India

• Sarwat Hazeeqa

  Hayatt Health Care & Azur Pharmaceuticals, Zaheerabad, Telangana- 502220, India

This study explores the prospective of risperidone-loaded β-cyclodextrin nanosponges as a therapeutic strategy for managing altered mental status (AMS) and delirium in cancer patients. Almost 87% of patients with advanced cancer experience AMS or delirium, significantly impacting prognosis and quality of life. The present study aims to enhance the solubility, bioavailability, and therapeutic effectiveness of second-generation antipsychotic medication risperidone (RSP), with poor aqueous solubility, it was encapsulated in β-cyclodextrin nanosponges. The nanosponges prepared by fusion technique using different β-CD: DPC molar ratios, were tested for their ability to encapsulation efficiency, drug loading, and dissolutions kinetics. Batch 1, (1:1 molar ratio) exhibits RSP loading capacity (454.2 µg/mg) and encapsulation efficiency (90.84%) along with DSC and FTIR also confirmed that the RSP was successfully encapsulated and without any chemical interactions. In vitro dissolution studies demonstrated a biphasic release profile, with an initial burst followed by sustained release, governed by Fickian diffusion as confirmed by release kinetics modeling. The improved solubility and dissolution profile of the nanosponges will be significant to improve risperidone delivery, ensuring better symptom management in a vulnerable population. These findings highlight the potential of β-cyclodextrin nanosponges as an innovative and adaptable platform for enhancing antipsychotic drug delivery.

LaHue SC, Douglas VC. Approach to altered mental status and inpatient delirium. Neurol Clin 2022; 40(1): 45-57. https://doi.org/10.1016/j.ncl.2021.08.004

El Majzoub I, Abunafeesa H, Cheaito R, Cheaito MA, Elsayem AF. Management of altered mental status and delirium in cancer patients. Ann Palliat Med 2019; 8(5). https://doi.org/10.21037/apm.2019.09.14

Bush SH, Tierney S, Lawlor PG. Clinical assessment and management of delirium in the palliative care setting. Drugs 2017; 77(15): 1623-1643. https://doi.org/10.1007/s40265-017-0804-3

Bellman V, Russell N, Depala K, Dellenbaugh A, Desai S, Vadukapuram R, Patel S, Srinivas S. Challenges in treating cancer patients with unstable psychiatric disorder. World J Oncol 2021; 12(5): 137-148. https://doi.org/10.14740/wjon1402

Bourgeois A, Horrill T, Mollison A, Stringer E, Lambert LK, Stajduhar K. Barriers to cancer treatment for people experiencing socioeconomic disadvantage in high-income countries: a scoping review. BMC Health Serv Res 2024; 24: 670. https://doi.org/10.1186/s12913-024-11129-2

Weinstein LC, Stefancic A, Cunningham AT, Hurley KE, Cabassa LJ, Wender RC. Cancer screening, prevention, and treatment in people with mental illness. CA Cancer J Clin 2016; 66(2): 134-151. https://doi.org/10.3322/caac.21334

Venkataramu VN, Ghotra HK, Chaturvedi SK. Management of psychiatric disorders in patients with cancer. Indian J Psychiatry 2022; 64(Suppl 2): S458-S472. https://doi.org/10.4103/indianjpsychiatry.indianjpsychiatry_15_22

Kishi Y, Kato M, Okuyama T, Thurber S. Treatment of delirium with risperidone in cancer patients. Psychiatry Clin Neurosci 2012; 66(5): 411-417. https://doi.org/10.1111/j.1440-1819.2012.02346.x

Chou FH, Tsai KY, Wu HC, Shen SP. Cancer in patients with schizophrenia: What is the next step? Psychiatry Clin Neurosci 2016; 70(11): 473-488. https://doi.org/10.1111/pcn.12420

Oystacher T, Blasco D, He E, Huang D, Schear R, McGoldrick D, Link B, Yang LH. Understanding stigma as a barrier to accessing cancer treatment in South Africa: implications for public health campaigns. Pan Afr Med J 2018; 29: 73. https://doi.org/10.11604/pamj.2018.29.73.14399

Grassi L, Riba MB. Disparities and inequalities in cancer care and outcomes in patients with severe mental illness: Call to action. Psychooncology 2021; 30(12): 1997-2001. https://doi.org/10.1002/pon.5853

Zhang X, Ma L. Antipsychotics and tumor suppressor gene activity in cancer patients with schizophrenia. Transl Psychiatry 2013; 3: e288.

Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y, Li Y. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct Target Ther 2021; 6(1): 263. https://doi.org/10.1038/s41392-021-00658-5

Eslami M, Memarsadeghi O, Davarpanah A, Arti A, Nayernia K, Behnam B. Overcoming chemotherapy resistance in metastatic cancer: a comprehensive review. Biomedicines 2024; 12(1): 183. https://doi.org/10.3390/biomedicines12010183

Watkins CC, Sawa A, Pomper MG. Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application. Transl Psychiatry 2014; 4(1): e350. https://doi.org/10.1038/tp.2013.119

Rathi R, Mehetre NM, Goyal S, Singh I, Huanbutta K, Sangnim T. Advanced drug delivery technologies for enhancing bioavailability and efficacy of risperidone. Int J Nanomedicine 2024; 19: 12871-12887. https://doi.org/10.2147/IJN.S492684

Alvarez-Herrera S, Rosel Vales M, Pérez-Sánchez G, Becerril-Villanueva E, Flores-Medina Y, Maldonado-García JL, Saracco-Alvarez R, Escamilla R, Pavón L. Risperidone decreases expression of serotonin receptor-2A (5-HT2A) and serotonin transporter (SERT) but not dopamine receptors and dopamine transporter (DAT) in PBMCs from patients with schizophrenia. Pharmaceuticals 2024; 17(2): 167. https://doi.org/10.3390/ph17020167

Moran-Gates T, Grady C, Shik Park Y, Baldessarini RJ, Tarazi FI. Effects of risperidone on dopamine receptor subtypes in developing rat brain. Eur Neuropsychopharmacol 2007; 17(6-7): 448-55. https://doi.org/10.1016/j.euroneuro.2006.10.004

Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology 1996; 124(1-2): 57-73. https://doi.org/10.1007/BF02245606

Pyrak B, Rogacka-Pyrak K, Gubica T, Szeleszczuk Ł. Exploring cyclodextrin-based nanosponges as drug delivery systems: understanding the physicochemical factors influencing drug loading and release kinetics. Int J Mol Sci 2024; 25(6): 3527. https://doi.org/10.3390/ijms25063527

Koppula S, Maddi S. Nanosponges in therapeutics: Current advancements and future directions in targeted drug delivery. J Drug Deliv Sci Technol 2024; 101(Pt B): 106258. https://doi.org/10.1016/j.jddst.2024.106258

Llave K, Cheng KK, Ko A, Pham A, Ericson M, Campos B, Perez-Gilbe HR, Kim JHJ. Promising directions: a systematic review of psychosocial and behavioral interventions with cultural incorporation for advanced and metastatic cancer. Int J Behav Med 2024; 31: 848-870. https://doi.org/10.1007/s12529-024-10264-8

Saokham P, Muankaew C, Jansook P, Loftsson T. Solubility of cyclodextrins and drug/cyclodextrin complexes. Molecules 2018; 23(5): 1161. https://doi.org/10.3390/molecules23051161

Rojek B, Bartyzel A, Sawicki W, Plenis A. DSC, TGA-FTIR and FTIR assisted by chemometric factor analysis and PXRD in assessing the incompatibility of the antiviral drug arbidol hydrochloride with pharmaceutical excipients. Molecules 2024; 29(1): 264. https://doi.org/10.3390/molecules29010264

Mennickent S, de Diego M, Liser B, Trujillo L. Stability indicating HPLC method for quantification of risperidone in tablets. J Chil Chem Soc 2018; 63(3): 4150. https://doi.org/10.4067/s0717-97072018000304150

Dedania ZR, Dedania RR, Sheth NR, Patel JB, Patel B. Stability indicating HPLC determination of risperidone in bulk drug and pharmaceutical formulations. Int J Anal Chem 2011; 2011: 124917. https://doi.org/10.1155/2011/124917

Kumar S, Sihag P, Trotta F, Rao R. Encapsulation of Babchi oil in cyclodextrin-based nanosponges: physicochemical characterization, photodegradation, and in vitro cytotoxicity studies. Pharmaceutics 2018; 10(4): 169. https://doi.org/10.3390/pharmaceutics10040169

Sbârcea L, Tănase IM, Ledeți A, Cîrcioban D, Vlase G, Barvinschi P, Miclău M, Văruţ RM, Suciu O, Ledeți I. Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex-Compatibility Study with Pharmaceutical Excipients. Molecules 2021; 26(6): 1690. https://doi.org/10.3390/molecules26061690

Alkilani AZ, Omar S, Nasereddin J, Hamed R, Obaidat R. Design of colon-targeted drug delivery of dexamethasone: Formulation and in vitro characterization of solid dispersions. Heliyon 2024; 10(14): e34212. https://doi.org/10.1016/j.heliyon.2024.e34212

Mekasha YT, Wondie Mekonen A, Nigussie S, et al. Modeling and comparison of dissolution profiles for different brands of albendazole boluses. BMC Pharmacol Toxicol 2024; 25: 48. https://doi.org/10.1186/s40360-024-00774-2

Sbârcea L, Tănase IM, Ledeți A, Cîrcioban D, Vlase G, Barvinschi P, Miclău M, Văruţ RM, Trandafirescu C, Ledeți I. Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies. Molecules 2020; 25(23): 5694. https://doi.org/10.3390/molecules25235694

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