Nanotechnology-enabled delivery of phytoconstituents: Recent developments, applications, and regulatory considerations

Abstract

Nanotechnology has revolutionized drug delivery, particularly through nanoformulations of phytoconstituents, enhancing their therapeutic potential. Despite their broad bioactivities, plant-based compounds often suffer from poor bioavailability and stability. Nanoformulations address these limitations by improving solubility, targeted delivery, and controlled release. This approach opens new possibilities for treating chronic diseases like cancer, diabetes, and neurodegenerative disorders. This review aims to examine recent advancements in nanotechnology-based formulation strategies designed to enhance the delivery, stability, and therapeutic efficacy of phytochemicals and also discusses regulatory issues, safety concerns, scalability, and cost-effectiveness. Emphasis was placed on nanoformulation techniques employed for key phytoconstituents such as curcumin, resveratrol, epigallocatechin gallate, and quercetin. The most commonly employed nanocarriers included polymeric nanoparticles, solid lipid nanoparticles, and liposomes. These formulations significantly improved the solubility, stability, and controlled release profiles of phytochemicals. In vitro and in vivo studies demonstrated enhanced anti-inflammatory, anticancer, and antioxidant activities. Moreover, surface-modified and targeted nanoparticles showed promise in increasing site-specific targeting and enhancing bioavailability of the encapsulated compounds. Nanoformulations present a promising strategy for overcoming the pharmacokinetic limitations of phytochemicals. Despite encouraging preclinical results, further studies are needed to address issues related to long-term safety, clinical efficacy, and regulatory approval for successful clinical translation.

Keywords

Phytoconstituents / Nanoformulations / Bioavailability enhancement / Nanotechnology / Personalized medicine / Cosmeceuticals / Nutraceuticals

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The article received no extramural funding.

Authors’ contributions

MDA contributed to the conception and design of the work, carried out the methodology, conducted the investigation, performed the formal analysis, and drafted the original manuscript. HM participated in data investigation, contributed to the formal analysis, and assisted in manuscript writing. SM was involved in the critical review and editing of the manuscript and contributed to the formal analysis. ZMS contributed to the critical revision and editing of the draft and participated in the formal analysis. AH performed critical review and edited the manuscript. YS contributed to the critical review, editing, and formal analysis. FS was involved in the review, editing, and formal analysis of the manuscript. All authors reviewed and approved the final version of the manuscript for publication.

Declaration of generative AI and AI-assisted technologies in the manuscript preparation process

During the preparation of this work, the authors used ChatGPT to paraphrase certain sections of the manuscript, without involvement in data collection, analysis, or any other scientific work. The authors reviewed and edited the content and take full responsibilities for the publication.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

The authors sincerely thank Universiti Malaya for their support.

References

[1] Shaikh JR, Patil M. Qualitative tests for preliminary phytochemical screening: An overview. Int J Chem Stud 2020; 8(2):603-608.

[2] Shariare MH, Kazi M. Phospholipid based nano drug delivery systems of phytoconstituents. In: Ahmad U, Faheem Haider M, Smart drug delivery. London: Intechopen; 2022, p. 101-120.

[3] Khan AR, Yang X, Fu M, Zhai G. Recent progress of drug nanoformulations targeting to brain. J Control Release 2018; 291:37-64.

[4] Tan ZS, Vasan RS. Thyroid function and Alzheimer’s disease. J Alzheimers Dis 2009; 16(3):503-507.

[5] Ansari MD, Saifi Z, Pandit J, Khan I, Solanki P, Sultana Y, et al. Spanlastics a novel nanovesicular carrier: Its potential application and emerging trends in therapeutic delivery. AAPS PharmSciTech 2022; 23(4). doi: 10.1208/s12249-022-02217-9.

[6] Karuppaiah A, Babu D, Selvaraj D, Natrajan T, Rajan R, Gautam M, et al. Building and behavior of a pH-stimuli responsive chitosan nanoparticles loaded with folic acid conjugated gemcitabine silver colloids in MDA-MB-453 metastatic breast cancer cell line and pharmacokinetics in rats. Eur J Pharm Sci 2021; 165. doi: 10.1016/J.EJPS.2021.105938.

[7] S MS, Naveen NR, Rao GK, Gopan G, Chopra H, Park MN, et al. A spotlight on alkaloid nanoformulations for the treatment of lung cancer. Front Oncol 2022; 12. doi: 10.3389/FONC.2022.994155/PDF.

[8] Barnett C, Joubert F, Iliopoulou A, Álvarez RS, Pasparakis G. Photochemical internalization using natural anticancer drugs, antimetabolites, and nanoformulations: A systematic study against breast and pancreatic cancer cell lines. Mol Pharm 2023; 20(3):1818-1841.

[9] AbouAitah K, Higazy IM, Swiderska-Sroda A, Abdelhameed RM, Gierlotka S, Mohamed TA, et al. Anti-inflammatory and antioxidant effects of nanoformulations composed of metal-organic frameworks delivering rutin and/or piperine natural agents. Drug Deliv 2021; 28(1):1478-1495.

[10] AbouAitah K, Stefanek A, Higazy IM, Janczewska M, Swiderska-Sroda A, Chodara A, et al. Effective targeting of colon cancer cells with piperine natural anticancer prodrug using functionalized clusters of hydroxyapatite nanoparticles. Pharmaceutics 2020; 12(1). doi: 10.3390/PHARMACEUTICS12010070.

[11] Cordell GA, Quinn-Beattie ML, Farnsworth NR. The potential of alkaloids in drug discovery. Phytother Res 2001; 15(3):183-205.

[12] Davatgaran-Taghipour Y, Masoomzadeh S, Farzaei MH, Bahramsoltani R, Karimi-Soureh Z, Rahimi R, et al. Polyphenol nanoformulations for cancer therapy: Experimental evidence and clinical perspective. Int J Nanomedicine 2017; 12:2689-2702.

[13] Funes L, Fernández-Arroyo S, Laporta O, Pons A, Roche E, Segura-Carretero A, et al. Correlation between plasma antioxidant capacity and verbascoside levels in rats after oral administration of lemon verbena extract. Food Chem 2009; 117(4):589-598.

[14] Shivani, Singh G, Narwal S, Chopra B, Dhingra A. Quercetin-based nanoformulation: A potential approach for cancer treatment. Anticancer Agents Med Chem 2023; 23(18):1983-2007.

[15] Dwivedi K, Mandal AK, Afzal O, Altamimi ASA, Sahoo A, Alossaimi MA, et al. Emergence of nano-based formulations for effective delivery of flavonoids against topical infectious disorders. Gels 2023; 9(8). doi: 10.3390/GELS9080671.

[16] Mashwani ZUR, Khan MA, Khan T, Nadhman A. Applications of plant terpenoids in the synthesis of colloidal silver nanoparticles. Adv Colloid Interface Sci 2016; 234:132-141.

[17] Parveen R, Ahmad F, Iqbal Z, Singh M, Kamal Y, Ahmad S. Simultaneous estimation of anti-cancer terpenoids in pharmaceutical nanoformulation by RP-HPLC and HPTLC. Acta Chromatogr 2014; 26(2):391-400.

[18] Malla S, Neupane R, Boddu SHS, Abou-Dahech MS, Pasternak M, Hussein N, et al. Application of nanocarriers for paclitaxel delivery and chemotherapy of cancer. In: Swamy MK, Pullaiah T, Chen ZS (eds.) Paclitaxel:sources, chemistry, anticancer actions, and current biotechnology. Salt Lake City, USA: Academic Press; 2022, p. 73-127.

[19] Bag BG, Barai AC, Hasan SN, Panja SK, Ghorai S, Patra S. Terpenoids, nano-entities and molecular self-assembly. Pure and Applied Chemistry 2019; 92:567-577.

[20] Bag BG, Das S, Hasan SN, Barai AC, Ghorai S, Panja SK, et al. Terpenoids in early 21st century: From renewable functional nano-entities to advanced materials. Prayogik Rasayan 2018; 2(1). doi: 10.53023/P.RASAYAN-20171222.

[21] Felgines C, Fraisse D, Besson C, Vasson MP, Texier O. Bioavailability of lemon verbena (Aloysia triphylla) polyphenols in rats: Impact of colonic inflammation. Br J Nutr 2014; 111(10):1773-1781.

[22] Pandit J, Garg M, Jain NK, Palacios S, Silverman SL, De Villiers TJ, et al. Miconazole nitrate bearing ultraflexible liposomes for the treatment of fungal infection. Menopause 2015; 22(2):806-813.

[23] Naseri A, Holdt SL, Jacobsen C. Biochemical and nutritional composition of industrial red seaweed used in carrageenan production. J Aquat Food Prod Technol 2019; 28(9):967-973.

[24] Mahato SB. Glycosides, saponins and sapogenins. In: Sainsbury M (ed.) Second supplements to the 2nd edition of Rodd’s chemistry of carbon compounds. Amsterdam, Holland: Elsevier; 2008, p. 509-554.

[25] Penfold J, Thomas RK, Tucker I, Petkov JT, Stoyanov SD, Denkov N, et al. Saponin adsorption at the air-water interface-neutron reflectivity and surface tension study. Langmuir 2018; 34(32):9540-9547.

[26] Wang Y, Xu X, Gu Y, Cheng Y, Cao F. Recent advance of nanoparticle-based topical drug delivery to the posterior segment of the eye. Expert Opin Drug Deliv 2018; 15(7):687-701.

[27] Benalaya I, Alves G, Lopes J, Silva LR. A review of natural polysaccharides: Sources, characteristics, properties, food and pharmaceutical applications. Int J Mol Sci 2024; 25(2). doi: 10.3390/ijms25021322.

[28] Li J, Ahmed HH, Hussein AM, Kaur M, Jameel MK, Kaur H, et al. Advances in polysaccharide‐based materials for biomedical and pharmaceutical applications: A comprehensive review. Arch Pharm (Weinheim) 2024. doi: 10.1002/ARDP.202400854.

[29] Hsu CY, Allela OQB, Hussein AM, Mustafa MA, Kaur M, Alaraj M, et al. Recent advances in polysaccharide-based drug delivery systems for cancer therapy: A comprehensive review. Artif Cells Nanomed Biotechnol 2024; 52(1):564-586.

[30] Kareemi AF, Likhitkar S. Applications and advancements of polysaccharide-based nanostructures for enhanced drug delivery. Colloids Surf B Biointerfaces 2024; 238. doi: 10.1016/j.colsurfb.2024.113883.

[31] Hao Y, Ji Z, Zhou H, Wu D, Gu Z, Wang D, et al. Lipid-based nanoparticles as drug delivery systems for cancer immunotherapy. MedComm (Beijing) 2023; 4(4):e339.

[32] Hu YW, Du YZ, Liu N, Liu X, Meng TT, Cheng BL, et al. Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier. J Control Release 2015; 206:91-100.

[33] Fan S, Han H, Yan Z, Lu Y, He B, Zhang Q. Lipid-based nanoparticles for cancer immunotherapy. Med Rev 2023; 3(3):230-269.

[34] Ahmad N, Banala VT, Kushwaha P, Karvande A, Sharma S, Tripathi AK, et al. Quercetin-loaded solid lipid nanoparticles improve osteoprotective activity in an ovariectomized rat model: A preventive strategy for post-menopausal osteoporosis. RSC Adv 2016; 6(100):97613-97628.

[35] Obozina AS, Komedchikova EN, Kolesnikova OA, Iureva AM, Kovalenko VL, Zavalko FA, et al. Genetically encoded self-assembling protein nanoparticles for the targeted delivery in vitro and in vivo. Pharmaceutics 2023; 15(1). doi: 10.3390/PHARMACEUTICS15010231.

[36] Seth L, Bingham Ferlez KM, Kaba SA, Musser DM, Emadi S, Matyas GR, et al. Development of a self-assembling protein nanoparticle vaccine targeting Plasmodium falciparum circumsporozoite protein delivered in three army liposome formulation adjuvants. Vaccine 2017; 35(41):5448-5454.

[37] Majid H, Verma N, Bhandari S, Gupta S, Nidhi. A systematic review on safety and efficacy of Migalastat for the treatment of Fabry’s Disease. Expert Opin Pharmacother 2024; 25(6):769-782. doi: 10.1080/14656566.2024.2354466.

[38] Majid H, Masoom M, Khan MA, Garg A. Safety and efficacy of genistein in Sanfilippo syndrome-A systematic review. Curr Drug Ther 2023; 18(4). doi: 10.2174/1574885518666230313145936.

[39] Xu H, Yang Y. Nanoparticles derived from plant proteins for controlled release and targeted delivery of therapeutics. Nanomedicine 2015; 10(13):2001-2004.

[40] Mirza MA, Talegaonkar S, Iqbal Z. Quantitative analysis of itraconazole in bulk, marketed, and nano formulation by validated, stability indicating high performance thin layer chromatography. J Liq Chromatogr Relat Technol 2012; 35(11):1459-1480.

[41] El-Leithy ES, Abdel-Rashid RS. Lipid nanocarriers for tamoxifen citrate/coenzyme Q10 dual delivery. J Drug Deliv Sci Technol 2017; 41:239-250.

[42] Solanki P, Ansari MD, Alam MI, Aqil M, Ahmad FJ, Sultana Y. Precision engineering designed phospholipid-tagged pamidronate complex functionalized SNEDDS for the treatment of postmenopausal osteoporosis. Drug Deliv Transl Res 2023; 13(3):883-913.

[43] Ansari MD, Ahmed S, Imam SS, Khan I, Singhal S, Sharma M, et al. CCD based development and characterization of nano-transethosome to augment the antidepressant effect of agomelatine on Swiss albino mice. J Drug Deliv Sci Technol 2019; 54. doi: 10.1016/j.jddst.2019.101234.

[44] Pinkerton JV, Dalkin AC. Combination therapy for treatment of osteoporosis: A review. Am J Obstet Gynecol 2007; 197(6):559-565.

[45] Chime SA, Akpa PA, Attama AA. The utility of lipids as nanocarriers and suitable vehicle in pharmaceutical drug delivery. Curr Nanomater 2019; 4(3):160-175.

[46] Ramteke AS. Lipid nanobiotechnology: An alternative strategy to targeted drug and vaccine delivery system and its biomedical applications as nanomedicine. Int J Med Pharm Sci 2023; 13(5):1-9.

[47] Belal A, Mahmoud R, Mohamed EE, Farghali A, Abo El-Ela FI, Gamal A, et al. A novel hydroxyapatite/vitamin B12 nanoformula for treatment of bone damage: Preparation, characterization, and anti-arthritic, anti-inflammatory, and antioxidant activities in chemically induced arthritic rats. Pharmaceuticals 2023; 16(4). doi: 10.3390/PH16040551.

[48] Patel AD, Desai MA. Reduction in particle size of methylcobalamin using antisolvent crystallization. Mater Today Proc 2019; 32:431-436.

[49] Pandit J, Aqil M, Sultana Y. Nanoencapsulation technology to control release and enhance bioactivity of essential oils. In: Grumezescu AM (ed.) Encapsulations: Nanotechnology in the agri-food industry Volume 2. Salt Lake City, USA: Academic Press; 2016, p. 597-640.

[50] Granata G, Riccobene C, Napoli E, Geraci C. Polymeric nanocapsules containing fennel essential oil: Their preparation, physicochemical characterization, stability over time and in simulated gastrointestinal conditions. Pharmaceutics 2022; 14(4). doi: 10.3390/PHARMACEUTICS14040873.

[51] Mahomoodally MF, Sadeer N, Edoo M, Venugopala KN. The potential application of novel drug delivery systems for phytopharmaceuticals and natural extracts-current status and future perspectives. Mini Rev Med Chem 2020; 21(18):2731-2746.

[52] Singh D. Application of novel drug delivery system in enhancing the therapeutic potential of phytoconstituents. Asian J Pharm 2015. doi: 10.22377/AJP.V9I4.480.

[53] Ng PQ, Ling LSC, Chellian J, Madheswaran T, Panneerselvam J, Kunnath AP, et al. Applications of nanocarriers as drug delivery vehicles for active phytoconstituents. Curr Pharm Des 2020; 26(36):4580-4590.

[54] Kharbanda J, Mazumder R, Bhardwaj S, Mazumder A, Mishra R, Mishra R, et al. Phytoconstituents-based nanotherapeutic approach for the effective management of joint inflammatory condition: Arthritis. Curr Drug Targets 2024; 25(10):700-714.

[55] Siddiquee T, Bhaskaran NA, Nathani K, Sawarkar SP. Empowering lung cancer treatment: Harnessing the potential of natural phytoconstituent-loaded nanoparticles. Phytother Res 2024; 38(8):3899-3920.

[56] Poudyal A, Subba B, Bhattarai A, Regmi D, Tiwari B, Pradhan A, et al. Comprehensive review on phytosomes: A novel drug delivery system of phytoconstituents. Int J Life Sci Pharma Res 2022. doi: 10.22376/IJPBS/LPR.2022.12.5.P143-161.

[57] Mahmoudabad AG, Shirshahi V, Mehrabi M, Gheybi F, Gharravi AM, Salehi M, et al. Phytosome: An effective transdermal drug delivery system for phytoconstituents. Lett Drug Des Discov 2022; 20(8):1020-1030.

[58] Sohel M, Aktar S, Biswas P, Amin MA, Hossain MA, Ahmed N, et al. Exploring the anti-cancer potential of dietary phytochemicals for the patients with breast cancer: A comprehensive review. Cancer Med 2023; 12(13):14556-14583.

[59] Gilani SJ, Beg S, Kala C, Nomani MS, Mahapatra DK, Imam SS, et al. Chemically nano-engineered theranostics for phytoconstituents as healthcare application. Curr Biochem Eng 2020; 6(1):53-61.

[60] Godase SS, Kulkarni NS, Dhole SN. A comprehensive review on novel lipid-based nano drug delivery. Adv Pharm Bull 2024; 14(1):34-47.

[61] Alharbi WS, Almughem FA, Almehmady AM, Jarallah SJ, Alsharif WK, Alzahrani NM, et al. Phytosomes as an emerging nanotechnology platform for the topical delivery of bioactive phytochemicals. Pharmaceutics 2021; 13(9). doi: 10.3390/PHARMACEUTICS13091475.

[62] Babazadeh A, Zeinali M, Hamishehkar H. Nano-phytosome: A developing platform for herbal anti-cancer agents in cancer therapy. Curr Drug Targets 2018; 19(2):170-180.

[63] Nadeem M, Majid H, Ansari MD, Ahmad FJ, Parvez S, Akhtar M, et al. Development and optimization of piracetam and shatavarin IV-loaded nanoemulsion for alzheimer’s disease therapy: In silico and experimental analysis. ACS Omega 2025; 10(9):9132-9153.

[64] Alam P, Imran M, Ali A, Majid H. Cananga odorata (Ylang-Ylang) essential oil containing nanoemulgel for the topical treatment of scalp psoriasis and dandruff. Gels 2024; 10(5):303.

[65] Gnananath K, Nataraj KS, Rao BG. Phospholipid complex technique for superior bioavailability of phytoconstituents. Adv Pharm Bull 2017; 7(1):35-42.

[66] Imran M, Riaz T, Majid H, Maqsood S. Identification of botanicals using molecular biotechnology. Polim Med 2023; 53(1):69-79.

[67] Imran Mohd, Majid H, Ali M, Qadir A. Phytochemical screening of Solanum xanthocarpum and its xanthine oxidase inhibitory activity. Biol Sci 2022; 2(3):311-323.

[68] Ansari MD, Majid H, Khan A, Sultana Y. Clinical frontiers of metabolic bone disorders: A comprehensive review. Metab Target Organ Damage 2023;4:2. doi: 10.20517/mtod.2023.38.

[69] Nodirahon A, Majid H, Waghdhare S, Vohora D, Nidhi. The effect of sodium glucose co-transport 2 inhibitors on cognitive impairment and depression in type 2 diabetes mellitus patients. Clin Epidemiol Glob Health 2024;26. doi: 10.1016/J.CEGH.2024.101555.

[70] Zhang P, Steinborn B, Lächelt U, Zahler S, Wagner E. Lipo-oligomer nanoformulations for targeted intracellular protein delivery. Biomacromolecules 2017; 18(8):2509-2520.

[71] Lin W, Ma G, Yuan Z, Qian H, Xu L, Sidransky E, et al. Development of zwitterionic polypeptide nanoformulation with high doxorubicin loading content for targeted drug delivery. Langmuir 2019; 35(5):1273-1283.

[72] Dahalia M, Gupta S, Majid H, Vohora D, Nidhi. Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in Mice. Front Pharmacol 2025; 15. doi: 10.3389/fphar.2024.1528032.

[73] Majid H, Masoom M, Bansal N, Ahmad W, Khan MF, Farooqui S, et al. Spectrum of infections in different regimens of post-induction chemotherapy in acute myeloid leukemia (de-novo): A comparative retrospective study. Heliyon 2024; 10(3):e24561.

[74] Khan WU, Salman M, Ali M, Majid H, Yar MS, Akhtar M, et al. Neuroprotective effects of sulforaphane in a rat model of Alzheimer’s disease induced by Aβ (1-42) peptides. Neurochem Int 2024; 179. doi: 10.1016/j.neuint.2024.105839.

[75] Roy M, Majid H, Khan P, Sharma N, Kohli S, Islam SU, et al. CTX-1 and TRACP-5b as biomarkers for osteoporosis risk in type 2 diabetes mellitus: A cross-sectional study. J Diabetes Metab Disord 2024; 23(2):2055-2064.

[76] Pathak M, Majid H, Khan P, Masoom M, Parveen R, Kapur P, et al. Effect of sodium-glucose co-transporter 2 inhibitors on MCP-1 and uromodulin levels in patients with type 2 diabetes mellitus. Clin Epidemiol Glob Health 2025; 31. doi: 10.1016/j.cegh.2024.101888.

[77] Shishir MRI, Karim N, Xu Y, Xie J, Chen W. Improving the physicochemical stability and functionality of nanoliposome using green polymer for the delivery of pelargonidin-3-O-glucoside. Food Chem 2021; 337. doi: 10.1016/J.FOODCHEM.2020.127654.

[78] Chen C, Ma T, Tang W, Wang X, Wang Y, Zhuang J, et al. Reversibly-regulated drug release using poly(tannic acid) fabricated nanocarriers for reduced secondary side effects in tumor therapy. Nanoscale Horiz 2020; 5(6):986-998.

[79] Kaur H, Ghosh S, Kumar P, Basu B, Nagpal K. Ellagic acid-loaded, tween 80-coated, chitosan nanoparticles as a promising therapeutic approach against breast cancer: In-vitro and in-vivo study. Life Sci 2021; 284. doi: 10.1016/J.LFS.2021.119927.

[80] Tyagi K, Masoom M, Majid H, Garg A, Bhurani D, Agarwal NB, et al. Role of cytokines in chemotherapy-related cognitive impairment of breast cancer patients: A systematic review. Curr Rev Clin Exp Pharmacol 2023; 18(2):110-119.

[81] Shidhaye S, Vaidya R, Sutar S, Patwardhan A, Kadam V. Solid lipid nanoparticles and nanostructured lipid carriers - innovative generations of solid lipid carriers. Curr Drug Deliv 2008; 5(4):324-331.

[82] Pierre MBR, Dos Santos Miranda Costa I. Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Arch Dermatol Res 2011; 303(9):607-621.

[83] Belliveau NM, Huft J, Lin PJ, Chen S, Leung AK, Leaver TJ, et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 2012; 1(8). doi: 10.1038/mtna.2012.28.

[84] Devina Verma, Mirza MA, Taleuzzaman M, Khuroo T, Talegaonkar S, Kumar R, et al. Development and validation of reversed phase HPLC method for the simultaneous detection of lactone and carboxylate forms of topotecan along with thymoquinone: Application to nanoparticulate anticancer formulation system. J Anal Chem 2020; 75(4):503-509.

[85] Arifin DY, Lee LY, Wang CH. Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems. Adv Drug Delivery Rev 2006; 58(12-13):1274-1325.

[86] Iqbal Z. Oral formulation of paclitaxel and erlotinib polymeric nanoparticles: A potential combination to treat breast cancer. Biomed J Sci Tech Res 2020; 31(4):29-32.

[87] Ahmed S, Gull A, Aqil M, Danish Ansari M, Sultana Y. Poloxamer-407 thickened lipid colloidal system of agomelatine for brain targeting: Characterization, brain pharmacokinetic study and behavioral study on Wistar rats. Colloids Surf B Biointerfaces 2019; 181:426-436.

[88] Sariem CN, Nanlir ZS, Banwat SB, Dapar MP. Factors influencing tuberculosis medication adherence: A cognitive intervention in a resource limited setting. World J Pharm Sci 2019; 3(9):1912-1920.

[89] Ahmed S, Mahmood S, Ansari MD, Gull A, Sharma N, Sultana Y. Nanostructured lipid carrier to overcome stratum corneum barrier for the delivery of agomelatine in rat brain; formula optimization, characterization and brain distribution study. Int J Pharm 2021; 607. doi: 10.1016/j.ijpharm.2021.121006.

[90] Müller RH, Petersen RD, Hommoss A, Pardeike J. Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Deliv Rev 2007; 59(6):522-530.

[91] Kesharwani P, Jain K, Jain NK. Dendrimer as nanocarrier for drug delivery. Prog Polym Sci 2014; 39(2):268-307.

[92] Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U. Dendrimer nanoarchitectures for cancer diagnosis and anticancer drug delivery. Drug Discov Today 2017; 22(2):314-326.

[93] Ansari MD khan I, Solanki P, Pandit J, Jahan RN, Aqil M, et al. Fabrication and optimization of raloxifene loaded spanlastics vesicle for transdermal delivery. J Drug Deliv Sci Technol 2022; 68. doi: 10.1016/j.jddst.2022.103102.

[94] Morimoto N, Endo T, Ohtomi M, Iwasaki Y, Akiyoshi K. Hybrid nanogels with physical and chemical cross-linking structures as nanocarriers. Macromol Biosci 2005; 5(8):710-716.

[95] Radha R, Paul V, Anjum S, Bouakaz A, Pitt WG, Husseini GA. Enhancing Curcumin’s therapeutic potential in cancer treatment through ultrasound mediated liposomal delivery. Sci Rep 2024; 14(1). doi: 10.1038/s41598-024-61278-x.

[96] Kumar A, Kurmi BD, Singh A, Singh D. Potential role of resveratrol and its nano-formulation as anti-cancer agent. Explor Target Antitumor Ther 2022; 3(5):643-658.

[97] Vishwas S, Gulati M, Kapoor B, Gupta S, Singh SK, Awasthi A, et al. Expanding the arsenal against Huntington’s disease-herbal drugs and their nanoformulations Curr Neuropharmacol 2021; 19(7):957-989.

[98] McCubrey JA, Lertpiriyapong K, Steelman LS, Abrams SL, Yang LV, Murata RM, et al.Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY) 2017; 9(6):1477.

[99] Alyasiri FJ, Ghobeh M, Tabrizi MH. Preparation and characterization of allicin-loaded solid lipid nanoparticles surface-functionalized with folic acid-bonded chitosan: In vitro anticancer and antioxidant activities. Front Biosci (Landmark Ed) 2023; 28(7). doi: 10.31083/J.FBL2807135.

[100] Jagaran K, Habib S, Singh M. Bio-inspired polymeric solid lipid nanoparticles for sirna delivery: Cytotoxicity and cellular uptake in vitro. Polymers (Basel) 2024; 16(23). doi: 10.3390/POLYM16233265.

[101] Ahmad H, Khandelwal K, Samuel SS, Tripathi S, Mitra K, Sangwan RS, et al. Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats. Drug Deliv 2016; 23(7):2630-2641.

[102] Murray CJL, Afshin A, Alam T, Ashbaugh C, Barthelemy C, Biehl M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396(10258):1204-1222.

[103] Mehta P, Bothiraja C, Mahadik K, Kadam S, Pawar A. Phytoconstituent based dry powder inhalers as biomedicine for the management of pulmonary diseases. Biomed Pharmacother 2018; 108:828-837.

[104] Cheng Z, Fobian SF, Gurrieri E, Amin M, D’Agostino VG, Falahati M, et al. Lipid-based nanosystems: The next generation of cancer immune therapy. J Hematol Oncol 2024; 17(1):53. doi: 10.1186/s13045-024-01574-1.

[105] Wu S, Yang X, Lu Y, Fan Z, Li Y, Jiang Y, et al. A green approach to dual-drug nanoformulations with targeting and synergistic effects for cancer therapy. Drug Deliv 2017; 24(1):51-60.

[106] Sharma P, Maheshwari R, Tekade M, Tekade R. Nanomaterial based approaches for the diagnosis and therapy of cardiovascular diseases. Curr Pharm Des 2015; 21(30):4465-4478.

[107] Jayakodi S, Kim H, Menon S, Shanmugam VK, Choi I, Sekhar MR, et al. Preparation of novel nanoformulation to enhance efficacy in the treatment of cardiovascular disease. Biomimetics 2022; 7(4). doi: 10.3390/BIOMIMETICS7040189.

[108] Smith BR. Nanotherapeutics for cardiovascular disease. Nat Rev Cardiol 2021; 18(9):617-618.

[109] Campisi A, Sposito G, Pellitteri R, Santonocito D, Bisicchia J, Raciti G, et al. Effect of unloaded and curcumin-loaded solid lipid nanoparticles on tissue transglutaminase isoforms expression levels in an experimental model of Alzheimer’s disease. Antioxidants 2022; 11(10). doi: 10.3390/antiox11101863.

[110] Bhattacharya T, Soares GABE, Chopra H, Rahman MM, Hasan Z, Swain SS, et al. Applications of phyto-nanotechnology for the treatment of neurodegenerative disorders. Materials 2022; 15(3). doi: 10.3390/MA15030804.

[111] Singh S, Semwal BC, Sharma H, Sharma D. Impact of phytomolecules with nanotechnology on the treatment of inflammation. Curr Bioact Compd 2023; 19(10). doi: 10.2174/1573407219666230807150030.

[112] Kim TH, Kang MS, Mandakhbayar N, El-Fiqi A, Kim HW. Anti-inflammatory actions of folate-functionalized bioactive ion-releasing nanoparticles imply drug-free nanotherapy of inflamed tissues. Biomaterials 2019; 207:23-38.

[113] Patil KR, Mahajan UB, Unger BS, Goyal SN, Belemkar S, Surana SJ, et al. Animal models of inflammation for screening of anti-inflammatory drugs: Implications for the discovery and development of phytopharmaceuticals. Int J Mol Sci 2019; 20(18). doi: 10.3390/IJMS20184367.

[114] Bisht G, Singh AK, Kumar A, Kumar P. A mechanistic study of the antibacterial activity of phytoconstituents of Pyracantha crenulata by using molecular docking studies. Curr Chin Chem 2022; 2(3). doi: 10.2174/2666001602666220722112558.

[115] Chakrabarty S, Swain SS, Mishra MP. Quantitative phytochemical investigation, antibacterial potency, and drug-ability assessment of three indian medicinal plants leaf extracts using bioinformatics tools. Int J Exp Res Rev 2024; 42:351-364.

[116] Das P, Kumar K, Nambiraj A, Awasthi R, Dua K, Malipeddi H. Antibacterial and in vitro growth inhibition study of struvite urinary stones using Oxalis corniculata Linn. leaf extract and its biofabricated silver nanoparticles. Recent Pat Drug Deliv Formul 2018; 12(3):170-178.

[117] Mushtaq W, Ishtiaq M, Maqbool M, Mazhar MW, Casini R, Abd-ElGawad AM, et al. Green synthesis of zinc oxide nanoparticles using Viscum album extracts: Unveiling bioactive compounds, antibacterial potential, and antioxidant activities. Plants (Basel) 2023; 12(11). doi: 10.3390/PLANTS12112130.

[118] Crous C, Pretorius J, Petzer A. Overview of popular cosmeceuticals in dermatology. Skin Health Dis 2024; 4(2). doi: 10.1002/SKI2.340.

[119] Rahimpour Y, Hamishehkar H. Liposomes in cosmeceutics. Expert Opin Drug Deliv 2012; 9(4):443-455.

[120] Ganesan P, Choi DK. Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy. Int J Nanomed 2016; 11:1987-2007.

[121] Puglia C, Santonocito D. Cosmeceuticals: Nanotechnology-based strategies for the delivery of phytocompounds. Curr Pharm Des 2019; 25(21):2314-2322.

[122] Singh J, Kaur L, McCarthy OJ. Factors influencing the physico-chemical, morphological, thermal and rheological properties of some chemically modified starches for food applications—A review. Food Hydrocoll 2007; 21(1):1-22.

[123] Shah S, Nene S, Rangaraj N, Raghuvanshi RS, Singh SB, Srivastava S. Bridging the gap: Academia, industry and FDA convergence for nanomaterials. Drug Dev Ind Pharm 2020; 46(11):1735-1746.

[124] Zhang L, Xia Y. Scaling up the production of colloidal nanocrystals: Should we increase or decrease the reaction volume? Adv Mater 2014; 26(16):2600-2606.

[125] Heo DN, Min KH, Choi GH, Kwon IK, Park K, Lee SC. Scale-up production of theranostic nanoparticles. In: Chen XY, Wong S ( Salt Lake City,eds.) Cancer theranostics. USA: Academic Press; 2014, p. 457-470.

[126] Doan VD, Luc VS, Nguyen TLH, Nguyen TD, Nguyen TD. Utilizing waste corn-cob in biosynthesis of noble metallic nanoparticles for antibacterial effect and catalytic degradation of contaminants. Environ Sci Pollut Res 2020; 27(6):6148-6162.

[127] Ankamwar B, Lai TC, Huang JH, Liu RS, Hsiao M, Chen CH, et al. Biocompatibility of Fe₃O₄ nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells. Nanotechnology 2010; 21(7). doi: 10.1088/0957-4484/21/7/075102.

[128] Luo C, Sun J, Du Y, He Z. Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy. J Control Release 2014; 176:94-103.

[129] Zhao X, Yang CX, Chen LG, Yan XP. Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy. Nat Commun 2017;8. doi: 10.1038/NCOMMS14998.

[130] Veeranarayanan S, Poulose AC, Mohamed MS, Varghese SH, Nagaoka Y, Yoshida Y, et al. Synergistic targeting of cancer and associated angiogenesis using triple-targeted dual-drug silica nanoformulations for theragnostics. Small 2012; 8(22):3476-3489.