Definition and Prevalence of Hypertension : Hypertension is a chronic medical condition characterized by persistently elevated arterial blood pressure, typically defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg in adults ⁷.It represents one of the most prevalent non-communicable diseases globally, affecting approximately 1.4 billion people and contributing to over 10 million deaths annually due to cardiovascular complications such as stroke, myocardial infarction, and renal failure ^8,9.The growing prevalence is attributed to urbanization,  sedentary  lifestyle,  and  dietary habits, making hypertension a global public-health challenge ¹⁰

Pathophysiology and Current Pharmacological Approaches : The pathophysiology of hypertension is multifactorial, involving genetic predisposition, overactivation of the renin– angiotensin–aldosterone system (RAAS), increased sympathetic activity, endothelial dysfunction, and oxidative stress ¹¹.Current pharmacological management includes diuretics, β-blockers, calcium-channel blockers, ACE inhibitors, angiotensin-II receptor blockers (ARBs), and direct vasodilators, either as monotherapy or in combination ^12.Although these drugs are effective, their pharmacokinetic limitations and poor patient adherence often compromise long-term blood-pressure control ¹³.

Challenges in Existing Antihypertensive Therapies: Conventional antihypertensive drugs frequently suffer from low aqueous solubility, poor oral bioavailability, rapid first-pass metabolism, and short biological half-life, resulting in variable plasma concentrations and suboptimal therapeutic outcomes ¹⁴. Moreover, the need for multiple daily doses and the incidence of systemic side effects (e.g., hypotension, dizziness, or electrolyte imbalance) further reduce patient compliance. These challenges emphasize the need for innovative drug-delivery platforms that can sustain drug release and improve target specificity.

Rationale for Using Nanoparticle-Based Drug Delivery: Nanoparticle-based drug-delivery systems (NDDS) offer novel solutions to overcome the pharmacokinetic drawbacks of conventional therapy. By reducing particle size to the nanometres range, NDDS enhance drug solubility, permeability, and retention, while allowing controlled or sustained release ¹⁶. Furthermore, surface modification (PEGylation or ligand  attachment)  enables  targeted  vascular delivery, minimizing systemic toxicity and maximizing therapeutic efficacy ^{17 ,18}.

Nanotechnology in Drug Delivery: An Overview:

Concept and Evolution of Nanotechnology in Medicine: Nanotechnology involves the design and application of materials at the nanometres scale (1–100 nm) to improve diagnosis and therapy ^19. Since the introduction of liposomes and polymeric nanoparticles in the 1970s, nanomedicine has evolved to include lipid carriers, dendrimers, micelles, and metallic nanoparticles for targeted and sustained drug delivery ²⁰.

Basic Characteristics of Nanoparticles: Nanoparticles possess a small size, high surface area, and modifiable surface charge, allowing better interaction with biological membranes ²¹ They exhibit biocompatibility, stability, and the ability to encapsulate both hydrophilic and hydrophobic drugs, protecting them from degradation and enhancing bioavailability ²².

Mechanisms of Nanoparticle-Mediated Drug Delivery: Drug transport occurs through enhanced permeability and retention (EPR) effect, enabling passive accumulation at disease sites ²³ Functionalization with ligands or polymers enables active targeting to specific receptors, while controlled-release properties ensure sustained therapeutic levels and reduced dosing frequency ²⁴.

Types of Nanoparticles Used in Hypertension Treatment:

1. Polymeric Nanoparticles: Polymeric nanoparticles are solid colloidal systems made from biodegradable or biocompatible polymers such as PLGA, Eudragit, and Chitosan, widely used for controlled and targeted drug delivery ²⁵.

Methods of Preparation: They can be prepared by techniques such as emulsion solvent evaporation (for PLGA and Eudragit systems) and ionic gelation (for chitosan nanoparticles), which allow precise control over particle size and drug-loading efficiency ²⁶

Applications in Antihypertensive Drug Delivery:

Polymeric nanoparticles enhance the bioavailability and sustained release of poorly soluble antihypertensive drugs like Nicardipine, Losartan, and Captopril ²⁷. They reduce dosing frequency, improve patient compliance, and can be modified for vascular or endothelial targeting, offering more consistent blood-pressure control ²⁸.

2. Lipid-Based Nanocarriers: Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) are lipid-based delivery systems that enhance the solubility, stability, and bioavailability of poorly water-soluble antihypertensive drugs ²⁹. They offer controlled release, protect drugs from degradation, and improve lymphatic uptake. Examples include SLN formulations of carvedilol and losartan, which demonstrate prolonged antihypertensive activity.
3. Liposomes and Noisome: Liposomes are spherical  vesicles  composed  of  phospholipid bilayers, while niosomes are their non-ionic surfactant analogy ³¹ Both systems show high encapsulation efficiency and allow for controlled and targeted delivery of antihypertensive drugs. Liposomal formulations of enalapril and captopril have shown enhanced absorption and reduced dosing frequency ³².
4. Metallic and Inorganic Nanoparticles: Gold, silica, and iron oxide nanoparticles have emerged as potential carriers for vascular-targeted drug delivery, due to their unique magnetic or optical properties ³³. They enable site-specific accumulation in hypertensive tissues and can be functionalized with ligands for endothelial targeting. However, biocompatibility and long- term safety remain key concerns requiring further evaluation ³⁴.
5. Nanosuspensions and Nano emulsions: These systems consist of drug particles dispersed in a suitable medium, improving dissolution of poorly soluble antihypertensive agents ³⁵. Techniques such as high-pressure homogenization and ultrasonication are commonly used. For example, Nicardipine nanosuspensions have shown improved bioavailability and extended blood- pressure control compared to conventional tablets

Fig 1. Types of Nanoparticles Used in Hypertension Treatment

Method of Preparation of Nanoparticles:

1. Emulsion Solvent Evaporation Technique:

This method is based on forming an emulsion of a polymer–drug solution in an organic solvent with an aqueous phase containing a stabilizer, followed by evaporation of the solvent, resulting in nanoparticle formation^37.

Fig 2. Emulsion Solvent Evaporation Technique

Procedure: -

1. The drug and polymer (e.g., PLGA, PLA, or PCL) are dissolved in a volatile organic solvent such as dichloromethane or ethyl acetate.
2. This polyvinyl alcohol (PVA) under high-speed homogenization or ultrasonication.
3. The solvent is then evaporated under reduced pressure or continuous stirring, leading to nanoparticle solidification.
4. The nanoparticles are collected by centrifugation, washed, and lyophilized for storage^38.

2. Ionic Gelation Method: The ionic gelation method is based on the electrostatic interaction between oppositely charged polymers or polyelectrolytes, leading to the formation of nanoparticles through cross-linking without the use of organic solvents or high temperatures³⁹

Procedure: -

1. Polymer Solution Preparation: A natural polymer such as chitosan (positively charged) is dissolved in a dilute acidic aqueous solution.
2. Cross-Linking Agent Preparation: A negatively charged agent such as sodium tripolyphosphate (TPP) is prepared in water.
3. Nanoparticle Formation: The TPP solution is added dropwise to the chitosan solution under continuous stirring. Electrostatic interactions between –NH?? groups of chitosan and –PO?³? groups of TPP cause spontaneous nanoparticle formation.
4. Purification: The resulting suspension is centrifuged and washed to remove unreacted materials.⁴⁰

Fig 3. Ionic gelation Method

3. Solvent Diffusion and Nanoprecipitation Method: This technique relies on the precipitation of polymer and drug from an organic solvent (miscible with water) into an aqueous phase, leading to the spontaneous formation of nanoparticles due to supersaturation and diffusion effects.⁴¹

Procedure: -

1. Organic Phase Preparation: The drug and polymer are dissolved in a partially water-miscible solvent (e.g., acetone, ethanol).
2. Aqueous Phase Preparation: A stabilizer or surfactant (e.g., PVA, poloxamer) is dissolved in water to prevent particle aggregation.
3. Diffusion / Nanoprecipitation: The organic phase is added dropwise into the aqueous phase under constant stirring Rapid diffusion of solvent into water causes supersaturation and instant nanoparticle formation.
4. Solvent Removal: The organic solvent is evaporated under reduced pressure, leaving stable nanoparticles in suspension.
5. Purification and Drying: Nanoparticles are collected by centrifugation, washed, and lyophilized for storage.⁴²

Fig 4. Solvent Diffusion and Nanoprecipitation Method

4. High-Pressure Homogenization (HPH) Method: High-Pressure Homogenization is based on forcing a drug–lipid mixture through a narrow gap under high pressure, creating intense shear forces and cavitation that break down particles to the nanometer range. It is widely used for lipid- based nanoparticles.⁴³

Procedure: -

1. Pre-emulsion Formation: The melted lipid phase containing the drug is dispersed in an aqueous surfactant solution using a high-speed stirrer to form a coarse emulsion.
2. High-Pressure Homogenization: The pre- emulsion is passed several times (3–10 cycles) through a high-pressure homogenizer at 100–1500 bar. The mechanical forces reduce droplet size to nanoscale.
3. Cooling and Solidification: The hot Nano emulsions is cooled to room temperature (or below lipid melting point) to solidify the lipid phase, forming solid lipid nanoparticles (SLNs) or nanostructured lipid carriers (NLCs).
4. Purification: The suspension is filtered and stored for further use. ⁴⁴

Fig 5. High pressure homogenization Method

5. Melt emulsification: The melt emulsification technique involves melting a lipid matrix containing the drug and dispersing it into a hot aqueous surfactant solution to form an emulsion. Upon cooling, the lipid phase solidifies into nanoparticles, encapsulating the drug.⁴⁵

Procedure: -

1. Melting of Lipid and Drug: The lipid (e.g., glyceryl monostearate, stearic acid) is heated above its melting point, and the drug is dissolved or dispersed in this molten lipid.
2. Emulsification: The molten lipid–drug mixture is added to a hot aqueous surfactant solution under continuous stirring or sonication to form a hot oil- in-water (O/W) emulsion.

Fig 6. Melt Emulsification Method

3. Cooling: The resulting emulsion is rapidly cooled to room temperature or below the lipid’s melting point, leading to solidification of lipid droplets into nanoparticles.
4. Collection and Purification:The formed nanoparticles are separated (e.g., by centrifugation or filtration) and washed to remove unencapsulated materials.⁴⁶

Table 1. Comparative Analysis for Antihypertensive Drugs:

Evaluation and Characterization of Nanoparticles:

The evaluation and characterization of nanoparticles are essential to ensure their quality, stability, and therapeutic performance. Various physicochemical and analytical parameters are assessed as follows:

1. Particle Size, Zeta Potential, and Polydispersity Index (PDI): These parameters are determined using Dynamic Light Scattering (DLS).

Particle size - influences drug release rate, biodistribution, and cellular uptake.

Zeta potential - indicates surface charge and predicts the stability of the nanoparticle suspension; higher absolute values denote better stability.

PDI - reflects the uniformity of particle size distribution; values below 0.3 indicate a monodisperse system.⁴⁷

2. Surface Morphology (SEM/TEM): Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) provide information on the surface structure, shape, and morphology of nanoparticles. TEM also offers insights into internal structure and particle aggregation behavior.⁴⁸
3. Drug Loading and Entrapment Efficiency: These parameters determine the amount of drug incorporated within nanoparticles. They are calculated using spectroscopic or chromatographic methods (e.g., UV–Vis, HPLC). High entrapment efficiency ensures optimal therapeutic effect and sustained release.⁴⁹
4. In Vitro Drug Release Studies: Conducted using dialysis membrane or diffusion cell methods, these studies evaluate the rate and mechanism of drug release from nanoparticles, simulating physiological conditions. Results help in predicting in vivo performance and release kinetics.⁵⁰

5. Stability Studies: Stability testing assesses changes in particle size, zeta potential, drug content, and morphology under various storage conditions (temperature, humidity, light). It ensures long-term consistency and shelf life of formulations.⁵¹
6. Compatibility Studies (FTIR, DSC): Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) are used to analyze possible interactions between the drug and excipients. FTIR detects chemical bonding changes, while DSC identifies thermal transitions indicating physical          or         chemical incompatibilities.⁵²

Fig 7. Evaluation and characterization of Nanoparticles

Pharmacokinetic Aspects:

1. Impact of Nanoparticles on Drug Absorption and Bioavailability: Nanoparticles significantly influence the pharmacokinetic behavior of drugs by enhancing their solubility, permeability, and stability ⁵³ Due to their nanoscale size and large surface area, they can improve dissolution rates and facilitate absorption through biological membranes. Additionally, nanoparticles protect drugs from enzymatic degradation and first-pass metabolism, leading to improved systemic bioavailability. Lipid-based and polymeric nanoparticles have been shown to enhance oral absorption of poorly water-soluble drugs such as antihypertensives and anticancer agents⁵³
2. Sustained and Targeted Release Profiles: Nanocarrier systems provide controlled and site- specific drug release, reducing fluctuations in plasma concentration and minimizing dosing frequency⁵⁴ Sustained release is achieved through diffusion- or degradation-controlled mechanisms within the nanoparticle matrix. Surface functionalization with ligands (e.g., antibodies, peptides) enables targeted delivery to specific tissues or receptors, thereby improving therapeutic efficacy and reducing systemic side effects ⁵⁴

Mechanism of Targeted Nanoparticles Delivery In Hypertension

Passive Targeting (Enhanced Permeability and Retention Effect: Passive targeting utilizes the Enhanced Permeability and Retention (EPR) effect, where nanoparticles preferentially accumulate in hypertensive or inflamed vascular tissues due to leaky endothelium and impaired lymphatic drainage⁵⁵ This phenomenon allows nanoparticles within the size range of 10–200 nm to penetrate and remain in diseased vascular regions, improving drug localization without requiring specific ligands. Such systems enhance therapeutic efficiency and reduce systemic side effects.⁵⁵

Active Targeting (Ligand/Receptor-Mediated Delivery:  Active  targeting  involves  surface functionalization of nanoparticles with ligands such as antibodies, peptides, aptamers, or small molecules that specifically bind to overexpressed receptors in hypertensive tissues (e.g., angiotensin II type 1 receptors, endothelial adhesion molecules). This approach ensures cell-specific internalization and enhanced therapeutic concentration at target sites. Examples include angiotensin-targeted liposomes and peptide- modified nanoparticles ^56.

Fig 9. Application of nanoparticles in the hypertension management

CHALLENGES AND LIMITATION:

1. Toxicity & biocompatibility:

What: Nanoparticles can produce dose- and material-dependent toxicity (oxidative,stress, inflammation, genotoxicity, organ accumulation) that varies with size, shape, surface chemistry and dose. This makes safety prediction difficult from in-vitro data alone.

Why it matters: Unexpected toxicity blocks translation to clinic and raises regulatory hurdles.

Mitigations: thorough physico-chemical characterization, standardized in-vitro / in-vivo testing  cascades,  ADME  and  long-term biodistribution studies, and safer-by-design surface chemistries. ⁵⁸

2. Scale-up & reproducibility challenges: What: Many lab synthesis methods don’t translate directly to industrial scale — batch variability, control of critical quality attributes (size, PDI, surface properties), reproducibility and process robustness are recurring problems. Equipment, solvent handling, and process parameters often change product behaviour during scale-up.

Why it matters: Poor reproducibility raises costs, slows regulatory approval, and can change safety/efficacy profiles

Mitigations: adopt scalable manufacturing platforms         (continuous                          manufacturing, microfluidics, high-shear mixing), implement in- process controls and PAT (process analytical technology), and early engagement with manufacturing experts.⁵⁹

3. Regulatory & ethical considerations

What: Existing pharmaceutical frameworks (ICH, FDA, EMA) are not always specific enough for nanomaterials; regulators request additional characterization and risk assessment. Questions such as classification (device vs drug), lot comparability, long-term safety and environmental impact complicate approval pathways.

Why it matters: Unclear regulatory expectations lead to delays, additional studies and uncertain commercial paths.

Mitigations: follow FDA/EMA nanotechnology guidance, early regulatory engagement (pre-IND / scientific advice), transparent reporting of characterization and non-clinical data, and ethical review for human and environmental risks. ⁶⁰

4. Cost-effectiveness      &      manufacturing economics:

What: Nanomedicines can be expensive to develop and produce (specialized equipment, raw materials, tight QC). Limited comparative effectiveness data versus standard therapies makes it hard to demonstrate value to payers.

Why it matters: High manufacturing costs and uncertain reimbursement reduce commercial attractiveness and slow adoption.

Mitigations: early health-economic modeling, process intensification to lower per-unit cost, demonstrating clear clinical advantages (reduced dosing, fewer side-effects, better adherence) and lifecycle cost analyses. ⁶¹

Table 3: Challenges and Limitations of Nanoparticle-Based Drug Delivery Systems

FUTURE PROSPECTIVE:

1. Personalized nanomedicine in hypertension:

Precision or personalized nanomedicine aims to match nanoparticle formulations (drug choice, dose, targeting ligand, release profile) to patient- specific features such as genetics, comorbidities, endothelial phenotype and pharmacokinetics —enabling optimized blood-pressure control and fewer adverse effects. Approaches include pharmacogenomic-guided selection of antihypertensives combined with patient-tuned nanoformulations and theranostic nanoparticles that both monitor and treat vascular dysfunction. Early translational work and reviews highlight the conceptual framework and proof-of-principle platforms for tailoring nanomedicines to individual patients.⁶²

2. Smart and stimuli-responsive nanoparticles:

Stimuli-responsive or “smart” nanocarriers release drug payloads in response to physiological triggers (pH, redox state, enzymatic activity, temperature) or external cues (ultrasound, light, magnetic field). For hypertension this opens opportunities for on- demand vasodilator release at sites of vascular inflammation or endothelial dysfunction, reducing systemic exposure and orthostatic side effects. Recent advances in biodegradable, tunable polymers and composite nanostructures make clinically-relevant responsive systems more feasible. ⁶³

3. Clinical     translation     and     regulatory advancements:

The pathway from bench to clinic for nanomedicines is maturing: guideline documents, regulatory reflection papers, and translational frameworks now emphasize standardized characterization, robust preclinical models, quality-by-design, and early regulatory engagement. ⁶⁴ These developments reduce uncertainty for developers and provide clearer expectations for comparability, safety testing and manufacturing controls — accelerating clinical trials and approval for well-characterized nanoparticle therapeutics. Nevertheless, harmonization across regions and validated, high- throughput safety assays remain important needs.65

CONCLUSION:

Nanoparticle-based drug delivery systems offer a promising and innovative approach for the effective management of hypertension. Over the last decade, extensive research has focused on the development of various nanocarriers—including lipid-based, polymeric, and inorganic nanoparticles—that improve the solubility, stability, and targeted delivery of antihypertensive drugs. These nanosystems have demonstrated enhanced pharmacokinetic profiles, reduced dosing frequency, and minimized systemic toxicity, thereby addressing several limitations of conventional antihypertensive therapy Despite remarkable laboratory and preclinical advances, the clinical translation of nanomedicine for hypertension remains limited. Future success depends on rigorous translational and clinical research, standardized safety evaluation, reproducible large-scale manufacturing, and clear regulatory          pathways.                           Interdisciplinary collaboration among researchers, clinicians, and regulatory bodies will be vital to ensure safety, efficacy, and cost-effectiveness. Looking forward, the integration of personalized nanomedicine, stimuli-responsive “smart” nanoparticles, and digital health monitoring technologies may revolutionize hypertension therapy. These next- generation systems hold potential for real-time patient monitoring, adaptive drug delivery, and individualized treatment regimens—ushering in a new era of precision and patient-centered management of cardiovascular diseases.

REFERENCES

1. World Health Organization. Hypertension: Key Facts. WHO Report, 2023

2. Zhou, B. Et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2021: a pooled analysis of 1201 population- representative studies with 104 million participants. The Lancet (2021) 398 (10304): 957-980.
3. Gupta, S., & Kesarla, R. Limitations of conventional antihypertensive therapy and the potential of novel delivery systems. Current Hypertension Reviews (2020) 16 (3): 201-213.
4. Prerna, P., et al. A Comprehensive Review on Nanoparticles as Drug Delivery System and Their Role for Management of Hypertension. Current Pharmaceutical Biotechnology (2025).
5. Soomherun, N., et al. Encapsulation of Nicardipine Hydrochloride in PLGA nanoparticles for sustained antihypertensive effect. International Journal of Pharmaceutics (2017) 518 (1–2): 283-29
6. Cong, X., et al. Nanocarriers for targeted drug delivery in the vascular system: opportunities and challenges in clinical translation. Journal of Controlled Release (2024) 372: 548-562
7. WheltonPKetal.2017ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2018;71: e13–e115.
8. World Health Organization. Hypertension: Key Facts. 2023.
9. Zhou B et al. Worldwide trends in hypertension prevalence and progress in treatment and control, 1990–2021. Lancet. 2021;398(10304):957-980.
10. Forouzanfar MH et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;317(2):165-182.
11. Hall JE et al. Pathophysiology of hypertension: mechanisms of vascular dysfunction and organ damage. Hypertension. 2021;78(2):193-202.
12. Oparil S et al. Hypertension. Nat Rev Dis Primers. 2018; 4:18014.
13. Wiysonge CS et al. Adherence to antihypertensive therapy and its determinants: systematic review. BMC Cardiovasc Disord. 2021;21(1):27.
14. Gupta S & Kesarla R. Limitations of conventional antihypertensive therapy and potential of novel delivery systems. Curr Hypertens Rev. 2020;16(3):201-213.
15. Zaman MA et al. Side-effects and adherence issues in antihypertensive drug therapy. Eur Heart J Suppl. 2022;24(Suppl B): B60-B66.
16. Prerna P et al. A Comprehensive Review on Nanoparticles as Drug Delivery System and Their Role for Management of Hypertension. Curr Pharm Biotechnol. 2025.
17. Cong X et al. Nanocarriers for targeted drug delivery in the vascular system: opportunities and challenges. J Controlled Release. 2024; 372:548-562.
18. Jha G et al. Nanoparticle-based approaches for cardiovascular drug delivery. J Nanobiotechnol. 2024; 22:154.
19. Couvreur P, et al. Nanotechnology in medicine: new perspectives for drug delivery. Nat Rev Drug Discov. 2017;16(10):742-755.
20. Ventola CL. Progress in nanomedicine: challenges and opportunities. Pharm Ther. 2017;42(12):742-755.
21. Park K. Controlled drug delivery systems: past forward and future back. J Controlled Release. 2024; 375:182-198
22. Jha G et al. Nanoparticle-based approaches for cardiovascular drug delivery. J Nanobiotechnol. 2024; 22:154.
23. Prerna P et al. Nanoparticles as drug delivery systems in hypertension management. Curr Pharm Biotechnol. 2025.
24. Cong X et al. Nanocarriers for targeted drug delivery in the vascular system. J Controlled Release. 2024; 372:548-562.

24. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles-based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75(1):1-18.
25. Bala I, Hariharan S, Kumar MNVR. PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst. 2004;21(5):387-422.
26. Soomherun N, et al. Encapsulation of Nicardipine Hydrochloride in PLGA nanoparticles for sustained antihypertensive effect. Int J Pharm. 2017;518(1–2):283-
27. Prerna P et al. Nanoparticles as drug delivery systems in hypertension management. Curr Pharm Biotechnol. 2025.
28. Mehnert W, Mäder K. Solid lipid nanoparticles: Production, characterization and applications. Adv Drug Deliv Rev. 2012; 64:83–101.
29. Paliwal R, et al. SLNs of carvedilol for enhanced oral bioavailability. Eur J Pharm Biopharm. 2009;73(3):373–379.
30. Akbarzadeh A, et al. Liposome: Classification, preparation, and applications. Nanoscale Res Lett. 2013; 8:102.
31. Singh B, et al. Liposomal and niosomal formulations for antihypertensive drug delivery. Int J Pharm Sci Res. 2019;10(2):511– 519.
32. Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arab J Chem. 2019;12(7):908–931.
33. Mody VV, et al. Magnetic nanoparticles for targeted vascular therapy: Opportunities and challenges. Nanomedicine. 2014;9(9):1277–1292.
34. Patravale VB, et al. Nanosuspensions: A promising drug delivery strategy. J Pharm Pharmacol. 2004;56(7):827–840.
35. Patel D, et al. Development of nicardipine nanosuspension for enhanced oral bioavailability. Eur J Pharm Sci. 2018; 114:308–316
36. Bilati, U., Allémann, E., & Doelker, E. (2005). Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. European Journal of Pharmaceutical Sciences, 24(1), 67–75.
37. Kumari, A., Yadav, S. K., & Yadav, S. C. (2010).         Biodegradable polymeric nanoparticles-based drug delivery systems. Colloids and Surfaces B: Biointerfaces, 75(1), 1–18.
38. Calvo, P., Remuñán-López, C., Vila-Jato, J. L., & Alonso, M. J. (1997). Novel hydrophilic chitosan–polyethylene oxide nanoparticles as protein carriers. Journal of Applied Polymer Science, 63(1), 125–132.
39. Mohammed, M. A., Syeda, J. T. M., Wasan, K. M., & Wasan, E. K. (2017). An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics, 9(4), 53.
40. Fessi, H., Puisieux, F., Devissaguet, J. P., Ammoury, N., & Benita, S. (1989). Nanocapsule formation by interfacial polymer deposition following solvent displacement. International Journal of Pharmaceutics, 55(1), R1–R4.
41. Bilati, U., Allémann, E., & Doelker, E. (2005). Poly(D,L-lactide-co-glycolide) nanoparticle preparation by the nanoprecipitation method — influence of the solvent nature on particle size. Journal of Controlled Release, 101(1–3), 102–112
42. Müller, R. H., Mäder, K., & Gohla, S. (2000). Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art. European Journal of Pharmaceutics and Biopharmaceutics, 50(1), 161–177.