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  • Nanoemulsion-Based Targeted Drug Delivery Systems: Formulation Strategies, Optimization Techniques, And Therapeutic Applications in Neurodegenerative Diseases, Cancer, And Diabetes Mellitus

  • Department of Pharmaceutics Paavai College of Pharmacy and Research R. Puliyampatti, Namakkal, Tamilnadu, India

Abstract

Nanoemulsion-based drug delivery systems have emerged as advanced high-technology pharmaceutical platforms capable of overcoming major limitations associated with conventional drug delivery, including poor aqueous solubility, limited bioavailability, and lack of site specificity. Nanoemulsions are kinetically stable colloidal dispersions composed of two immiscible liquids stabilized by surfactants, with droplet sizes typically below 200 nm. Their nanoscale dimensions provide enhanced surface area, improved dissolution rates, and superior stability compared to conventional emulsions. Recent developments in nanotechnology have enabled the rational design and optimization of nanoemulsions using both high-energy and low-energy emulsification techniques. High-energy approaches such as ultrasonication, high-pressure homogenization, and micro fluidization generate intense shear forces to reduce droplet size, whereas low-energy methods rely on phase inversion and spontaneous emulsification mechanisms. Statistical optimization tools such as response surface methodology and Box–Behnken design further enhance formulation efficiency and reproducibility. Nanoemulsions demonstrate exceptional therapeutic potential in complex diseases such as neurodegenerative disorders, cancer, and diabetes mellitus. In neurodegenerative diseases, nanoemulsions facilitate nose-to-brain delivery, bypassing the blood–brain barrier and improving drug targeting. In oncology, nanoemulsions exploit the enhanced permeability and retention effect to increase tumor accumulation while minimizing systemic toxicity. In diabetes management, nanoemulsions improve oral bioavailability and therapeutic efficacy of antidiabetic agents, including natural polyphenols. This manuscript comprehensively reviews formulation principles, preparation methods,optimization strategies, and disease-specific applications of nanoemulsion-based drug delivery systems, highlighting their significance as next-generation pharmaceutical technologies.

Keywords

Nano emulsion; Targeted drug delivery; neurodegenerative diseases; Cancer therapy; Diabetes mellitus

Introduction

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Nanoemulsions are submicron colloidal systems consisting of oil and water phases stabilized by surfactants and co-surfactants, with droplet sizes typically ranging from 20 to 600 nm. Unlike conventional emulsions, Nanoemulsions exhibit superior kinetic stability, reduced gravitational separation, and enhanced bioavailability due to their nanoscale size and increased interfacial surface area [1,2,30].

The growing number of poorly water-soluble drugs in modern pharmacotherapy has intensified the need for innovative delivery systems capable of improving solubility, absorption, and therapeutic efficacy. Nanoemulsions offer multiple advantages, including ease of preparation, scalability, optical transparency, improved drug loading, and compatibility with multiple routes of administration [3–5].

Advances in nanotechnology have positioned Nanoemulsions as versatile carriers for targeted drug delivery in diseases requiring precise tissue localization, such as Alzheimer’s disease, Parkinson’s disease, cancer, and diabetes mellitus [6–9]. Their ability to cross biological barriers and provide controlled release makes Nanoemulsions a promising high-technology platform for pharmaceutical development.

2. CLASSIFICATION AND CHARACTERISTICS OF NANOEMULSIONS

Nanoemulsions are classified into oil-in-water (O/W), water-in-oil (W/O), and bi-continuous systems depending on the phase distribution. O/W Nanoemulsions are most commonly employed for oral, nasal, and parenteral delivery due to their low viscosity and patient acceptability.

Key physicochemical characteristics of Nanoemulsions include small droplet size, narrow size distribution, large interfacial area, optical clarity, and enhanced kinetic stability [1,2,30]. These properties significantly improve drug dissolution, absorption, and bioavailability.

Table 1 summarizes the classification, composition, and pharmaceutical relevance of Nano emulsion systems.

Type of Nano emulsion

Dispersed Phase

Continuous Phase

Key Characteristics

Pharmaceutical Relevance

Oil-in-Water (O/W)

Oil

Water

Low viscosity, high bioavailability, good patient compliance

Oral, nasal, parenteral delivery

Water-in-Oil (W/O)

Water

Oil

Sustained release, enhanced lipophilicity

Topical and transdermal delivery

Bi-continuous

Interconnected oil and water domains

—

High solubilization capacity

Advanced targeting applications

3. FORMULATION COMPONENTS

The formulation of stable Nanoemulsions depends on the careful selection of formulation components, including the oil phase, aqueous phase, surfactant, and co-surfactant [2,5]. The oil phase solubilizes lipophilic drugs, while surfactants reduce interfacial tension and stabilize nano-droplets. Co-surfactants enhance interfacial flexibility and promote spontaneous Nanoemulsions formation [4,7].

The hydrophilic–lipophilic balance (HLB) value of surfactants plays a crucial role in determining emulsion type, droplet size, and stability.

Table 2 lists commonly used formulation components and their pharmaceutical roles.

Component

Examples

Function

Oil phase

Medium-chain triglycerides, palm oil, isopropyl myristate

Solubilizes lipophilic drugs

Surfactants

Tween 80, Span 20

Reduces interfacial tension

Co-surfactants

Ethanol, propylene glycol

Enhances interfacial flexibility

Aqueous phase

Purified water, buffers

Continuous phase

4. METHODS OF NANO EMULSION PREPARATION

4.1 HIGH-ENERGY EMULSIFICATION TECHNIQUES

High-energy emulsification techniques utilize mechanical energy to break coarse emulsions into nanoscale droplets. These include high-pressure homogenization, ultrasonication, micro fluidization, and membrane emulsification.

Ultrasonication employs acoustic cavitation to reduce droplet size, while high-pressure homogenization forces emulsions through narrow gaps at high pressure, generating intense shear and turbulence [2,6,18].

4.2 LOW-ENERGY EMULSIFICATION TECHNIQUES

Low-energy methods rely on physicochemical changes in the system rather than external mechanical force. Phase inversion temperature and spontaneous emulsification are widely used low-energy techniques suitable for heat-sensitive drugs and large-scale manufacturing [7,30].

Table 3 compares high-energy and low-energy preparation methods.

Method Type

Technique

Principle

Advantages

Limitations

High-energy

High-pressure homogenization

Mechanical shear

Uniform droplet size

High energy consumption

High-energy

Ultrasonication

Acoustic cavitation

Simple laboratory method

Scale-up challenges

Low-energy

Phase inversion temperature

Thermodynamic changes

Suitable for heat-sensitive drugs

Limited formulation range

Low-energy

Spontaneous emulsification

Interfacial turbulence

Energy-efficient

Requires precise surfactant ratios

 

Figure 1 illustrates the structural organization of a Nanoemulsions system, while Figure 2 compares high-energy and low-energy preparation technique

5. OPTIMIZATION STRATEGIES

Figure 2 Schematic Representation of Nanoemulsion Structure

Optimization of Nanoemulsions formulations is essential to achieve desirable droplet size, polydispersity index, and stability. Response surface methodology and Box–Behnken design allow systematic evaluation of formulation variables with minimal experimental runs.

Design-Expert®-assisted optimization has been widely employed to enhance reproducibility and performance of Nanoemulsions-based drug delivery systems [6].

6. NANOEMULSIONS IN NEURODEGENERATIVE DISEASES

6.1 ALZHEIMER’S DISEASE

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline [12–14]. Nanoemulsions-based intranasal delivery systems bypass the blood–brain barrier via olfactory and trigeminal pathways, enhancing brain drug targeting [15–18].

Nanoemulsions containing curcumin and quercetin have demonstrated improved neuroprotection and therapeutic efficacy [19,20].

6.2 PARKINSON’S DISEASE

Parkinson’s disease involves degeneration of dopaminergic neurons, resulting in motor dysfunction [22–24]. Nanoemulsions-based delivery of levodopa, selegiline, and antioxidant compounds improves bioavailability, brain targeting, and behavioural outcomes [25–28].

Figure 3 depicts nose-to-brain drug delivery via Nanoemulsions.

Table 4 summarizes Nanoemulsions applications in neurodegenerative diseases.

Disease

Drug / Compound

Route

Therapeutic Outcome

Alzheimer’s disease

Curcumin, quercetin

Intranasal

Enhanced brain targeting

Parkinson’s disease

Levodopa

Oral / Nasal

Improved bioavailability

Parkinson’s disease

Selegiline

Intranasal

Enhanced behavioural performance

7. Nanoemulsions in Cancer Therapy

Nanoemulsions play a crucial role in cancer therapy through passive and active targeting mechanisms. The enhanced permeability and retention (EPR) effect enables selective accumulation of Nanoemulsions in tumor tissues due to leaky vasculature and poor lymphatic drainage [35,36].

Nanoemulsions-based delivery of paclitaxel, docetaxel, and doxorubicin has shown improved tumor targeting, reduced systemic toxicity, and enhanced anticancer efficacy [34,37,39].

Figure 4 illustrates tumour targeting via the EPR effect.

Table 5 summarizes Nanoemulsions-based anticancer applications.

Drug

Targeting Strategy

Outcome

Paclitaxel

Passive (EPR effect)

Increased tumor accumulation

Docetaxel

PEGylated Nanoemulsions

Prolonged circulation

Doxorubicin

Dual-targeting

Overcomes drug resistance

8. Nanoemulsions in Diabetes Mellitus

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycaemia. Nanoemulsions enhance oral bioavailability and therapeutic efficacy of antidiabetic agents.

Quercetin Nanoemulsions demonstrate improved glycaemic control, antioxidant activity, and pancreatic β-cell protection compared to conventional formulations [40,44,54].

Figure 5 illustrates the role of Nanoemulsions in diabetes management.

Table 6 summarizes Nanoemulsions applications in diabetes mellitus.

Active Compound

Benefit

Observed Effect

Quercetin

Improved solubility

Enhanced antidiabetic efficacy

Insulin alternatives

Oral delivery

Reduced injection dependency

9. ADVANTAGES AND LIMITATIONS

Nanoemulsions offer improved drug solubility, enhanced bioavailability, targeted delivery, and reduced toxicity [1,2]. However, challenges such as surfactant toxicity, long-term stability, and large-scale manufacturing remain.

10. FUTURE PERSPECTIVES

Future research should focus on stimuli-responsive Nanoemulsions, ligand-mediated targeting, and personalized drug delivery systems. Integration with smart nanotechnology platforms is expected to enhance clinical translation [38,39].

11. CONCLUSION

Nanoemulsions-based drug delivery systems represent a powerful high-technology platform capable of addressing critical challenges in pharmaceutical development. Their ability to enhance drug solubility, enable targeted delivery, and improve therapeutic efficacy across neurodegenerative diseases, cancer, and diabetes mellitus highlights their broad clinical potential. Continued innovation and clinical validation will further establish Nanoemulsions as key components of next-generation precision medicine

REFERENCES

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  3. Kim CK, Cho YJ, Gao ZG. Preparation and evaluation of biphenyl dimethyl dicarboxylate microemulsions for oral delivery. J Control Release. 2001; 70:149–155.
  4. Ahuja A, Ali J, Baboota S, Faisal MS, Shakeel F, Shafiq S. Stability evaluation of celecoxib Nanoemulsions containing Tween 80. Thai J Pharm Sci. 2008; 32:4–9.
  5. Sharma SN, Jain NK. A textbook of professional pharmacy. 1st ed. Vallabh Prakashan; 1985. p. 201.
  6. Tiwari SB, Amiji MM. Nanoemulsion formulations for tumor-targeted delivery. In: Nanotechnology in cancer therapy. Taylor & Francis Group; 2006. p. 723–739.
  7. El-Aasser MS, Lack CD, Vanderhoff JW, Fowkes FM. Miniemulsification process—different form of spontaneous emulsification. Colloids Surf. 1986; 29:103–118.
  8. Nirale P, Paul A, Yadav KS. Nanoemulsions for targeting the neurodegenerative diseases: Alzheimer's, Parkinson's and Ps. Life sciences. 2020 Mar 15; 245:117394.
  9. Bak TH, Chandran S. What wires together dies together: verbs, actions and neurodegeneration in motor neuron disease. Cortex. 2012;48(7):936–944.
  10. Nikalje AP. Nanotechnology and its applications in medicine. Med Chem. 2015;5(2):81–89.
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  12. Kurz A, Perneczky R. Novel insights for the treatment of Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(2):373–379
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  14. Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res. 2018;7.
  15. Shinde RL, Jindal AB, Devarajan PV. Microemulsions and nanoemulsions for targeted drug delivery to the brain. Curr Nanosci. 2011;7(1):119–133.
  16. Gabal YM, Kamel AO, Sammour OA, Elshafeey AH. Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route. Int J Pharm. 2014;473(1–2):442–457.
  17. Nasr M. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose-to-brain delivery. Drug Deliv. 2016;23(4):1444–1452
  18. Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B Biointerfaces. 2014; 113:330–337.
  19. Dhage MA, Kulkarni AS, Kokate TD, Jadhav SS, Mohite SV, Dongare PR, Chavan SA, Patil PB. Design, Formulation, and Optimization of Nano Emulsion-Based Nasal Delivery System of Quercetin for Alzheimer’s Therapy. Vascular and Endovascular Review. 2025 Nov 4;8(5s):468-78.
  20. Misra SK, Pathak K. Nose-to-brain targeting via nanoemulsion: significance and evidence. Colloids Interfaces. 2023; 7:23. doi:10.3390/colloids7010023.
  21. Singh D, Kapahi H, Rashid M, Prakash A, Majeed ABA, Mishra N. Recent prospective of surface engineered nanoparticles in the management of neurodegenerative disorders. Artif Cells Nanomed Biotechnol. 2016;44(3):780–791.
  22. Zijlmans JC, Daniel SE, Hughes AJ, Révész T, Lees AJ. Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov Disord. 2004;19(6):630–640.
  23. Fleming SM. Mechanisms of gene–environment interactions in Parkinson’s disease. Curr Environ Health Rep. 2017;4(2):192–199.
  24. Tab S. Parkinson’s disease (PD). In: The APRN and PA’s complete guide to prescribing drug therapy 2020. 2019. p. 368
  25. Zainol S, Basri M, Basri HB, Shamsuddin AF, Abdul-Gani SS, Karjiban RA, et al. Formulation optimization of a palm-based nanoemulsion system containing levodopa. Int J Mol Sci. 2012;13(10):13049–13064.
  26. Sa F, Guo BJ, Li S, Zhang ZJ, Chan HM, Zheng Y, et al. Pharmacokinetic study and optimal formulation of new anti-Parkinson natural compound schisantherin A. Parkinsons Dis. 2015;2015: Article ID 841371.
  27. Kumar S, Ali J, Baboota S. Design-Expert® supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced behavioural performance in Parkinson’s disease. Nanotechnology. 2016;27(43):435101.
  28. Gaba B, Khan T, Haider MF, Alam T, Baboota S, Parvez S, et al. Vitamin E-loaded naringenin nanoemulsion via intranasal delivery for the management of oxidative stress in a 6-OHDA Parkinson’s disease model. Biomed Res Int. 2019;2019: Article ID 2382564.
  29. Mahato R. Nanoemulsion as targeted drug delivery system for cancer therapeutics. Journal of pharmaceutical sciences and pharmacology. 2017 Jun 1;3(2):83-97.
  30. Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nano-emulsions. Adv Colloid Interface Sci. 2004; 108:303–318.
  31. Bielinska AU, Janczak KW, Landers JJ, Markovitz DM, Montefiori DC, Baker JR Jr. Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates. AIDS Res Hum Retroviruses. 2008; 24:271–281
  32. Tiwari S, Tan YM, Amiji M. Preparation and in vitro characterization of multifunctional nanoemulsions for simultaneous MR imaging and targeted drug delivery. J Biomed Nanotechnol. 2006; 2:217–224.
  33. Shi R, Hong L, Wu D, Ning X, Chen Y, Lin T, Fan D, Wu K. Enhanced immune response to gastric cancer-specific antigen peptide by coencapsulation with CpG oligodeoxynucleotides in nanoemulsion. Cancer Biol Ther. 2005; 4:218–224.
  34. Khandavilli S, Panchagnula R. Nanoemulsions as versatile formulations for paclitaxel delivery: peroral and dermal delivery studies in rats. J Invest Dermatol. 2007; 127:154–162.
  35. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000; 65:271–284.
  36. Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev. 2011; 63:131–135.
  37. Khalid MN, Simard P, Hoarau D, Dragomir A, Leroux JC. Long-circulating poly (ethylene glycol)-decorated lipid nanocapsules deliver docetaxel to solid tumors. Pharm Res. 2006; 23:752–758.
  38. Phillips MA, Gran ML, Peppas NA. Targeted nanodelivery of drugs and diagnostics. Nano Today. 2010; 5:143–159.
  39. Kim D, Lee ES, Oh KT, Gao ZG, Bae YH. Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH. Small. 2008; 4:2043–2050.
  40. Bastaki S. Diabetes mellitus and its treatment. International journal of Diabetes and Metabolism. 2005 Mar;13(3):111-34.
  41. World Health Organization. Diabetes mellitus. WHO Technical Report Series No. 727. Geneva: World Health Organization; 1985.
  42. Ahrén B, Corrigan CB. Intermittent need for insulin in a subgroup of diabetic patients in Tanzania. Diabet Med. 1984; 2:262–264.
  43. Zimmet P, Alberti KGMM, Shaw T. Global and social implications of the diabetes epidemic. Nature. 2001; 414:782–787.
  44. Miller CD, Phillips LS, Ziemer DC, et al. Hypoglycaemia in patients with type 2 diabetes mellitus. Arch Intern Med. 2001; 161:1653–1659.
  45. Pandit MK, Burke J, Gustafson AB. Drug-induced disorders of glucose tolerance. Ann Intern Med. 1993; 118:529–539.
  46. Raffel LJ, Scheuner MT, Rotter JI. Genetics of diabetes. In: Porte D Jr, Sherwin RS, editors. Ellenberg & Rifkin’s diabetes mellitus. 5th ed. Stamford (CT): Appleton & Lange; 1997. p. 401–454
  47. Lederman HM. Is maturity-onset diabetes of the young (MODY) more common in Europe than previously assumed? Lancet. 1995; 345:648.
  48. Bearse MA Jr, Han T, Schneck ME, et al. Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci. 2004; 45:3259–3265.
  49. Svensson M, Eriksson JW, Dahlquist G. Early glycemic control, age at onset, and development of microvascular complications in childhood-onset type 1 diabetes: a population-based study in northern Sweden. Diabetes Care. 2004; 27:955–962.
  50. Ramachandran A, Snehalatha C, Latha E, et al. Rising prevalence of NIDDM in an urban population in India. Diabetologia. 1997; 40:232–237.
  51. O’Dea K. Marked improvement in carbohydrate and lipid metabolism in diabetic Australian Aborigines after temporary reversion to traditional lifestyle. Diabetes. 1984; 33:596–603.
  52. Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the Da Qing IGT and Diabetes Study. Diabetes Care. 1997; 20:537–544.
  53. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002; 346:393–403.
  54. Mahadev M, Nandini HS, Ramu R, Gowda DV, Almarhoon ZM, Al-Ghorbani M, Mabkhot YN. Fabrication and evaluation of quercetin nanoemulsion: A delivery system with improved bioavailability and therapeutic efficacy in diabetes mellitus. Pharmaceuticals. 2022 Jan 5;15(1):70.

Reference

  1. Soni H, Sharma S. Current update on Nanoemulsions: a review. Sch. Int. J. Anat. Physiol. 2021;4(1):6-13.
  2. Jaiswal M, Dudhe R, Sharma PK. Nanoemulsions: an advanced mode of drug delivery system. 3 Biotech. 2015 Apr;5(2):123-7.
  3. Kim CK, Cho YJ, Gao ZG. Preparation and evaluation of biphenyl dimethyl dicarboxylate microemulsions for oral delivery. J Control Release. 2001; 70:149–155.
  4. Ahuja A, Ali J, Baboota S, Faisal MS, Shakeel F, Shafiq S. Stability evaluation of celecoxib Nanoemulsions containing Tween 80. Thai J Pharm Sci. 2008; 32:4–9.
  5. Sharma SN, Jain NK. A textbook of professional pharmacy. 1st ed. Vallabh Prakashan; 1985. p. 201.
  6. Tiwari SB, Amiji MM. Nanoemulsion formulations for tumor-targeted delivery. In: Nanotechnology in cancer therapy. Taylor & Francis Group; 2006. p. 723–739.
  7. El-Aasser MS, Lack CD, Vanderhoff JW, Fowkes FM. Miniemulsification process—different form of spontaneous emulsification. Colloids Surf. 1986; 29:103–118.
  8. Nirale P, Paul A, Yadav KS. Nanoemulsions for targeting the neurodegenerative diseases: Alzheimer's, Parkinson's and Ps. Life sciences. 2020 Mar 15; 245:117394.
  9. Bak TH, Chandran S. What wires together dies together: verbs, actions and neurodegeneration in motor neuron disease. Cortex. 2012;48(7):936–944.
  10. Nikalje AP. Nanotechnology and its applications in medicine. Med Chem. 2015;5(2):81–89.
  11. Srikanth M, Kessler JA. Nanotechnology—novel therapeutics for CNS disorders. Nat Rev Neurol. 2012;8(6):307.
  12. Kurz A, Perneczky R. Novel insights for the treatment of Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(2):373–379
  13. Kumar A. The role of oxidative stress in the pathophysiology of Alzheimer’s disease. EC Neurology. 2019; 11:672–680.
  14. Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res. 2018;7.
  15. Shinde RL, Jindal AB, Devarajan PV. Microemulsions and nanoemulsions for targeted drug delivery to the brain. Curr Nanosci. 2011;7(1):119–133.
  16. Gabal YM, Kamel AO, Sammour OA, Elshafeey AH. Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route. Int J Pharm. 2014;473(1–2):442–457.
  17. Nasr M. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose-to-brain delivery. Drug Deliv. 2016;23(4):1444–1452
  18. Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B Biointerfaces. 2014; 113:330–337.
  19. Dhage MA, Kulkarni AS, Kokate TD, Jadhav SS, Mohite SV, Dongare PR, Chavan SA, Patil PB. Design, Formulation, and Optimization of Nano Emulsion-Based Nasal Delivery System of Quercetin for Alzheimer’s Therapy. Vascular and Endovascular Review. 2025 Nov 4;8(5s):468-78.
  20. Misra SK, Pathak K. Nose-to-brain targeting via nanoemulsion: significance and evidence. Colloids Interfaces. 2023; 7:23. doi:10.3390/colloids7010023.
  21. Singh D, Kapahi H, Rashid M, Prakash A, Majeed ABA, Mishra N. Recent prospective of surface engineered nanoparticles in the management of neurodegenerative disorders. Artif Cells Nanomed Biotechnol. 2016;44(3):780–791.
  22. Zijlmans JC, Daniel SE, Hughes AJ, Révész T, Lees AJ. Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov Disord. 2004;19(6):630–640.
  23. Fleming SM. Mechanisms of gene–environment interactions in Parkinson’s disease. Curr Environ Health Rep. 2017;4(2):192–199.
  24. Tab S. Parkinson’s disease (PD). In: The APRN and PA’s complete guide to prescribing drug therapy 2020. 2019. p. 368
  25. Zainol S, Basri M, Basri HB, Shamsuddin AF, Abdul-Gani SS, Karjiban RA, et al. Formulation optimization of a palm-based nanoemulsion system containing levodopa. Int J Mol Sci. 2012;13(10):13049–13064.
  26. Sa F, Guo BJ, Li S, Zhang ZJ, Chan HM, Zheng Y, et al. Pharmacokinetic study and optimal formulation of new anti-Parkinson natural compound schisantherin A. Parkinsons Dis. 2015;2015: Article ID 841371.
  27. Kumar S, Ali J, Baboota S. Design-Expert® supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced behavioural performance in Parkinson’s disease. Nanotechnology. 2016;27(43):435101.
  28. Gaba B, Khan T, Haider MF, Alam T, Baboota S, Parvez S, et al. Vitamin E-loaded naringenin nanoemulsion via intranasal delivery for the management of oxidative stress in a 6-OHDA Parkinson’s disease model. Biomed Res Int. 2019;2019: Article ID 2382564.
  29. Mahato R. Nanoemulsion as targeted drug delivery system for cancer therapeutics. Journal of pharmaceutical sciences and pharmacology. 2017 Jun 1;3(2):83-97.
  30. Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nano-emulsions. Adv Colloid Interface Sci. 2004; 108:303–318.
  31. Bielinska AU, Janczak KW, Landers JJ, Markovitz DM, Montefiori DC, Baker JR Jr. Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates. AIDS Res Hum Retroviruses. 2008; 24:271–281
  32. Tiwari S, Tan YM, Amiji M. Preparation and in vitro characterization of multifunctional nanoemulsions for simultaneous MR imaging and targeted drug delivery. J Biomed Nanotechnol. 2006; 2:217–224.
  33. Shi R, Hong L, Wu D, Ning X, Chen Y, Lin T, Fan D, Wu K. Enhanced immune response to gastric cancer-specific antigen peptide by coencapsulation with CpG oligodeoxynucleotides in nanoemulsion. Cancer Biol Ther. 2005; 4:218–224.
  34. Khandavilli S, Panchagnula R. Nanoemulsions as versatile formulations for paclitaxel delivery: peroral and dermal delivery studies in rats. J Invest Dermatol. 2007; 127:154–162.
  35. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000; 65:271–284.
  36. Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev. 2011; 63:131–135.
  37. Khalid MN, Simard P, Hoarau D, Dragomir A, Leroux JC. Long-circulating poly (ethylene glycol)-decorated lipid nanocapsules deliver docetaxel to solid tumors. Pharm Res. 2006; 23:752–758.
  38. Phillips MA, Gran ML, Peppas NA. Targeted nanodelivery of drugs and diagnostics. Nano Today. 2010; 5:143–159.
  39. Kim D, Lee ES, Oh KT, Gao ZG, Bae YH. Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH. Small. 2008; 4:2043–2050.
  40. Bastaki S. Diabetes mellitus and its treatment. International journal of Diabetes and Metabolism. 2005 Mar;13(3):111-34.
  41. World Health Organization. Diabetes mellitus. WHO Technical Report Series No. 727. Geneva: World Health Organization; 1985.
  42. Ahrén B, Corrigan CB. Intermittent need for insulin in a subgroup of diabetic patients in Tanzania. Diabet Med. 1984; 2:262–264.
  43. Zimmet P, Alberti KGMM, Shaw T. Global and social implications of the diabetes epidemic. Nature. 2001; 414:782–787.
  44. Miller CD, Phillips LS, Ziemer DC, et al. Hypoglycaemia in patients with type 2 diabetes mellitus. Arch Intern Med. 2001; 161:1653–1659.
  45. Pandit MK, Burke J, Gustafson AB. Drug-induced disorders of glucose tolerance. Ann Intern Med. 1993; 118:529–539.
  46. Raffel LJ, Scheuner MT, Rotter JI. Genetics of diabetes. In: Porte D Jr, Sherwin RS, editors. Ellenberg & Rifkin’s diabetes mellitus. 5th ed. Stamford (CT): Appleton & Lange; 1997. p. 401–454
  47. Lederman HM. Is maturity-onset diabetes of the young (MODY) more common in Europe than previously assumed? Lancet. 1995; 345:648.
  48. Bearse MA Jr, Han T, Schneck ME, et al. Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci. 2004; 45:3259–3265.
  49. Svensson M, Eriksson JW, Dahlquist G. Early glycemic control, age at onset, and development of microvascular complications in childhood-onset type 1 diabetes: a population-based study in northern Sweden. Diabetes Care. 2004; 27:955–962.
  50. Ramachandran A, Snehalatha C, Latha E, et al. Rising prevalence of NIDDM in an urban population in India. Diabetologia. 1997; 40:232–237.
  51. O’Dea K. Marked improvement in carbohydrate and lipid metabolism in diabetic Australian Aborigines after temporary reversion to traditional lifestyle. Diabetes. 1984; 33:596–603.
  52. Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the Da Qing IGT and Diabetes Study. Diabetes Care. 1997; 20:537–544.
  53. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002; 346:393–403.
  54. Mahadev M, Nandini HS, Ramu R, Gowda DV, Almarhoon ZM, Al-Ghorbani M, Mabkhot YN. Fabrication and evaluation of quercetin nanoemulsion: A delivery system with improved bioavailability and therapeutic efficacy in diabetes mellitus. Pharmaceuticals. 2022 Jan 5;15(1):70.

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Thilagavathi S.
Corresponding author

Paavai College of Pharmacy and Research R. Puliyampatti, Namakkal, Tamilnadu, India

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Aruna M.
Co-author

Paavai College of Pharmacy and Research R. Puliyampatti, Namakkal, Tamilnadu, India

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Sakthivel M.
Co-author

Paavai College of Pharmacy and Research R. Puliyampatti, Namakkal, Tamilnadu, India

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Sivakumar R.
Co-author

Paavai College of Pharmacy and Research R. Puliyampatti, Namakkal, Tamilnadu, India

Thilagavathi S., Aruna M., Sakthivel M., Sivakumar R., A Nanoemulsion-Based Targeted Drug Delivery Systems: Formulation Strategies, Optimization Techniques, And Therapeutic Applications in Neurodegenerative Diseases, Cancer, And Diabetes Mellitus, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 6, 3493-3502. https://doi.org/ 10.5281/zenodo.20699214

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