A Comprehensive Review on Advances in Polymeric Nanoparticles for Drug Delivery: Formulation, Characterization, and Applications

Over the past few decades, there has been a significant research focus in the field of medication delivery utilizing nanoparticles as vehicles for small and big molecules. Polymeric nanoparticle systems from polymers that are both biodegradable and biocompatible are fascinating choices for regulated medication distribution and medication targeting. Polymeric nano-sized particles are particulate suspensions or solid particles with dimensions in the spectrum of 10-1000 nm. The medication is dissolved, caught, enclosed, or linked to a nanoparticle matrix. They have been employed in vivo to safeguard the chemical compound in the bloodstream, limit entry of the medication to the selected locations and to administer the medication at a regulated and steady pace to the location of effect. Different polymers have been utilized in delivery studies. since they can efficiently transport the medication to a specific location and thereby enhance the healing effect, whilst reducing adverse effects.

Based on polymer nanoparticles efficiently transport medications, proteins, and DNA aimed at specific cells and organs. Their nanometre-scale encourages efficient penetration across cells membranes and equilibrium in the circulatory system. Based on the technique of preparation Nanoparticles, nanospheres, or nanocapsules may be acquired. Nanospheres possess a monolithic structure. matrix arrangement where medications are distributed or adsorbed on their surfaces or contained within the particles. Nanocapsules serve as the vesicular system in where the medication is limited to a space made up of a inner fluid core encased by a polymeric membrane. In this instance, the active ingredient is typically dissolved in the inner core, but could also be adsorbed to the surface of the capsule ^[1].

The term “nanoparticle” includes both Nanocapsules and nanospheres, which differ in their structure. Nanocapsules consist of a lipid core where the medication is typically dissolved, enclosed by a polymeric coating that regulates the drug's release characteristics from the nucleus. Nanospheres consist of a continuous polymeric structure wherein the medication can be held within or adhered to their exterior. These two kinds of polymeric nanoparticles identified as a fundamental component of the reservoir system. Nanospheres rely on a continuous polymeric structure that can hold the drug within or adsorb it onto their surfaces surface. These two forms of polymeric nanoparticles are identified as a storage system (nanocapsule) and matrix structure (nanosphere) ^[2].

Figure 1. Types of polymeric nanoparticles

Figure 2. A schematic representation of the solvent evaporation technique.

Figure 3. A schematic representation of nanoprecipitation.

5. Spray Drying Method

In this approach, chitosan is initially dissolved in acetic acid; the drug is either dissolved or dispersed within the solution, and subsequently, an appropriate cross-linking agent is introduced; this solution or dispersion is then atomized in a stream of hot air. The atomization process results in the creation of small droplets, from which the solvent evaporates, resulting in the formation of free-flowing powders. The particle size is influenced by the size of the nozzle, the spray flow rate, the atomization pressure, the inlet air temperature, and the degree of cross-linking ^[20].

6. Ionotropic Gelation

The ionotropic gelation technique is a commonly employed method for creating polymeric nanoparticles. This approach relies on the ionic crosslinking of a polymer with multivalent counter-ions, which leads to the spontaneous generation of nanoparticles under mild, aqueous conditions, frequently at room temperature. The procedure entails the electrostatic interaction between species with opposite charges, such as cationic and anionic, resulting in gelation and the formation of nanoparticles that are appropriate for drug delivery and biomedical applications ^[21].

CHARACTERIZATION OF NANOPARTICLES

Nanoparticle characterization is a field of nanometrology that deals with the measurement of the physical and chemical properties of nanoparticles. Different types of characterization methods are used to characterize polymeric nanoparticles ^[22].

1. Particle Size

The most crucial factors for characterizing nanoparticles are their particle size distribution and morphology. Electron microscopy is used to determine both the shape and size of the particles. Nanoparticles are primarily utilized in drug delivery and targeting. Research has shown that the size of the particles influences the rate of drug release. Smaller particles provide a greater surface area, which means that a larger portion of the drug attached to them is exposed on the surface, resulting in quicker drug release ^[23].

2. Zeta Potential

Every NP possessing a net surface charge is enveloped in an ionic solution by a counteracting charged outer layer closely attached to the particle and an ionic electrical double layer slightly attached to the particle surrounding this layer. The zeta potential of a nanoparticle may exert a considerable influence on its actions within a medication delivery system. Particles at the nanoscale containing Zeta potentials exceeding ± 30 mV are regarded as strongly cationic and strongly anionic, correspondingly. Typically, nanoparticles exhibiting a greater zeta potential possess a more intense electrostatic repulsion, which can aid in stabilizing them and keeping them from compiling ^[24].

3. Fourier Transform Infrared (FTIR) spectroscopy

FTIR spectroscopy quantifies infrared light absorption across wavelengths to reveal functional groups and structural features in polymeric nanoparticles. It identifies distinct peaks for chemical bonds in the polymer and encapsulated drug, confirming their presence, interactions, effective loading, and molecular compatibility without degradation. FTIR also detects contaminants or structural changes from formulation. Thus, it ensures the chemical composition, stability, and suitability of nanoparticles for drug delivery ^[25].

4. X-ray diffraction (XRD)

X-ray diffraction (XRD) serves as a valuable technique for investigating the crystalline makeup of nanoparticles. It is employed to ascertain fundamental material characteristics, including crystal structure, crystallite dimensions, and internal strain. The specific diffraction patterns observed are contingent upon the crystal's arrangement and the wavelength of light that interacts with it. Diffraction arises from the constructive interference of X-rays reflected from various planes within the material's periodic lattice ^[26].

5. Scanning Electron Microscopy (SEM)

Scanning electron microscopy (SEM) facilitates morphological examination through direct visualization. While electron microscopy techniques offer significant benefits for morphological and sizing analyses, they yield restricted insights into size distribution and the actual average of a population. The average size determined by SEM aligns with findings from dynamic light scattering ^[27].

6. Differential Scanning Calorimetry (DSC)

It is a method that consistently assesses the observed specific heat of a system depending on the temperature. It is utilized to assess the stability and framework of nanoparticles and it is likewise utilized to ascertain the conformation, as the material transition will vary based on the nanoparticle formulation.

7. UV-Visible Spectroscopy

It is a type of spectroscopy that radiates light with wavelengths ranging from 190 to 800 nm, commonly utilized for measuring compounds density and additionally dimensions and form in certain instances. It possesses has been utilized to establish the conjugation and proportion of attachment of biomolecules to nanomedicines. It is the an easy, quick, and economical method that can be applied for different types of nanomaterials ^[28].

8.  In Vitro Drug Release

The Dissolution test apparatus was employed for the in vitro drug release investigations. The dissolution apparatus vessel was filled with the dissolution medium, and the drug's release was monitored at a predetermined rate to guarantee consistent agitation and avoid microbead sedimentation at a constant temperature. Throughout the dissolution process, aliquots were extracted at regular intervals and replenished with the same volume of fresh medium. These withdrawn samples were then filtered using Whatmann filter paper and diluted with the identical dissolution media. The absorbance was subsequently determined using a UV-Visible Spectrophotometer. The cumulative percentage of drug released was calculated at each time point, and a graph was generated ^[29].

APPLICATION

• PNPs are presently utilized as biomaterials because of their beneficial attributes regarding straightforward fabrication and enhancement, remarkable biocompatibility, high structural diversity, and notable bioinspired properties.
• Polymeric nanocarriers serve as methods to enhance the bioavailability of medications or targeted delivery, making them ideal for drug transportation.
• The biomedical use of PNPs for cancer treatment management, ocular administration, vaccine distribution, targeted cell therapy, antibiotic treatment, nutraceutical applications, etc.
• The biodegradability, biocompatibility, non-toxicity, extended circulation time, and wide range of therapeutic drug loading capabilities are some of the system's excellent features.
• The varying size and shape characteristics allow for tissue penetration via active and passive targeting, specific cellular/subcellular transport processes, and straightforward control of payload release ^[30].

FUTURE PERSPECTIVE

The future of polymeric nanoparticles (PNPs) in drug delivery appears extremely promising, driven by ongoing progress in polymer science, nanotechnology, and biomedical research. Recent advances are increasingly focused on developing stimuli-responsive nanoparticles that can release drugs in response to specific biological conditions such as pH, temperature, enzymes, or redox environments, leading to more precise and effective treatment at the target site. Another growing area of interest is the creation of surface-modified and ligand-targeted nanoparticles, which can selectively deliver drugs to cancer cells, inflamed tissues, or specific intracellular compartments, thereby reducing unwanted side effects. In addition, the combination of polymeric nanoparticles with gene therapy, CRISPR technology, and mRNA delivery systems is expected to significantly contribute to the advancement of personalized and precision medicine.

Future studies are likely to focus on environment-friendly, cost-effective, and scalable manufacturing techniques to support large-scale production and regulatory acceptance. The development of nanoparticles, capable of simultaneous diagnosis and therapy, will further enhance disease monitoring and treatment outcomes. Overall, polymeric nanoparticles are expected to play a vital role in next-generation drug delivery systems, offering safer, more efficient, and patient-specific therapeutic solutions for a broad range of medical applications.

CONCLUSION

Over the last several decades, scientists have explored alternative methods of delivering drugs to enhance the effectiveness of various medications. Nanotechnology is an intriguing and innovative area that holds promise for advancements in numerous applications within drug delivery in pharmaceutical research. Polymeric nanoparticles have gained considerable attention as an advanced and flexible drug delivery platform because of their small size, biocompatibility, and ability to deliver drugs in a controlled and targeted manner. Their distinctive physicochemical and biological properties allow them to efficiently carry a wide range of therapeutic agents, including drugs, proteins, and genetic material, across biological barriers while reducing unwanted systemic side effects. Both natural and synthetic polymers can be used to design polymeric nanoparticles with customized properties. Various preparation techniques make it possible to precisely control particle size, surface characteristics, and drug loading, while thorough characterization ensures their stability, safety, and overall performance as drug carriers.  In summary, polymeric nanoparticles offer clear advantages in improving therapeutic effectiveness, enhancing bioavailability, and minimizing adverse effects. With ongoing research and technological progress, these nano systems are expected to play an increasingly important role in future pharmaceutical and biomedical applications, leading to safer, more targeted, and patient-friendly treatment strategies.

REFERENCES

1. Dadwal, M., Solan, D. and Pradesh, H., 2014. Polymeric nanoparticles as promising novel carriers for drug delivery: an overview. Journal of Advanced Pharmacy Education & Research Jan-Mar, 4(1).
2. Carreiró, F., Oliveira, A.M., Neves, A., Pires, B., Nagasamy Venkatesh, D., Durazzo, A., Lucarini, M., Eder, P., Silva, A.M., Santini, A. and Souto, E.B., 2020. Polymeric nanoparticles: Production, characterization, toxicology and ecotoxicology. Molecules, 25(3731).
3. Mohanraj, V.J. and Chen, Y.J.T.J.O.P.R., 2006. Nanoparticles-a review. Tropical journal of pharmaceutical research, 5(1), pp.561-573.
4. Vyas S.P., Khar R.K. Targeted and controlled drug delivery system. 1st ed. New Delhi: CBS Publication and Distribution; 2000, 332-381.
5. D. Sleep, Albumin and its application in drug delivery, Expert Opin. Drug Delv. 12 (2015) 793–812.
6. P.O. Boamah, J. Onumah, W.O. Aduguba, K.G. Santo, Application of depolymerized chitosan in crop production, Int. J. Biol. Macromol. 4 (2023), 123858.
7. H. Singh, V. Kumar, Cellulosic nanowhiskers: preparation and drug delivery application, Curr. Drug Deliv. 10 (2021) 1426–1434.
8. P. Zarrintaj, S. Manouchehri, Z. Ahmadi, M.R. Saeb, A.M. Urbanska, D.L. Kaplan, M. Mozafari, Agarose-based biomaterials for tissue engineering, Carbohy, Polymers 1 (2018) 66–84.
9. E. Montes, Dextran: sources, structures, and properties, Polysaccha 3 (2021) 554–565.
10. N. More, M. Avhad, S. Utekar, A. More, Polylactic acid (PLA) membrane—significance, synthesis, and applications, Polym. Bullet. 2 (2023) 1117–1153.
11. C.R. Devi, R. Ray, S. Koduri, A.K. Moharana, D. Ts, Clinical equivalence of polyglycolic acid suture and polyglactin 910 suture for subcutaneous tissue closure after cesarean delivery: a single-blind randomized study. medical devices, Evid. Res. 31 (2023) 27–36.
12. V.J. Mkhabela, S.S. Ray, Poly ( ε-caprolactone) nanocomposite scaffolds for tissue engineering: a brief overview, J. Nanosci. Nanotechnol. 14 (2014) 535–545.
13. T.S. Gaaz, A.B. Sulong, M.N. Akhta, A.A. Kadhum, A.B. Mohamad, A.A. Amiery, Properties and applications of polyvinyl alcohol, halloysite nanotubes and their nanocomposites, Molecules 12 (2015) 22833–22847.
14. F. Danhier, E. Ansorena, J.M. Silva, R. Coco, A. Breton A, V. Preat, PLGA-based nanoparticles. an overview of biomedical applications, J. Control. Rel. 2 (2012) 505–522.
15. Kreuter, J. (1994) 'Nanoparticles', in Kreuter, J. (ed.) *Colloidal Drug Delivery Systems*. New York: Marcel Dekker, pp. 219–342.
16. Zambaux M., Bonneaux F., Gref R. Influence of experimental parameters on the characteristics of poly (lactic acid) nanoparticles prepared by double emulsion method. J. Control. Release 1998; 50:31-40.
17. Zhang Q., Shen Z., Nagai T. Prolonged hypoglycaemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats. Int. J. Pharm. 2001; 218:75-80.
18. Mittal G., Sahana D.K., Bhardwaj V., Ravi Kumar M.N. Estradiol loaded PLGA nanoparticles for oral administration: Effect of polymer molecular weight and copolymer composition on release behaviour in vitro and in vivo. J. Control. Release 2007; 119:77-85.
19. Govender T., Stolnik S., Garnett MC., Illum L., Davis S.S. PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J. Control. Release 1999; 57(2):171-185.
20. Sinha S., Muthu M.S. Preparation and characterisation of nanoparticles containing an atypical anti-psychotic agent. Nanomedicine (Lond) 2007; 2:233-40.
21. 21] Hoang, N.H., Le Thanh, T., Sangpueak, R., Treekoon, J., Saengchan, C., Thepbandit, W., Papathoti, N.K., Kamkaew, A. and Buensanteai, N., 2022. Chitosan nanoparticles-based ionic gelation method: a promising candidate for plant disease management. Polymers, 14(4), p.662.
22. Mondal, D., Griffith, M. and Venkatraman, S.S., 2016. Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges. International Journal of Polymeric Materials and Polymeric Biomaterials, 65(5), pp.255-265.
23. Redhead, H.M., Davis, S.S. and Illum, L., 2001. Drug delivery in poly (lactide-co glycolide) nanoparticles surface modified with poloxamer 407 and poloxamine 908: in vitro characterisation and in vivo evaluation. Journal of Controlled Release, 70(3), pp.353-363.
24. Öztürk, K., Kaplan, M. and Çalış, S., 2024. Effects of nanoparticle size, shape, and zeta potential on drug delivery. International journal of pharmaceutics, 666, p.124799.
25. Shukla, U., 2025. Fourier transform infrared spectroscopy: A power full method for creating fingerprint of molecules of nanomaterials. Journal of Molecular Structure, 1322, p.140454.
26. Katmıs, A., Fide, S., Karaismailoglu, S. and Derman, S., 2018. Synthesis and characterization methods of polymeric nanoparticles. Characterization and Application of Nanomaterials, 1(4).
27. Eaton, P., Quaresma, P., Soares, C., Neves, C., De Almeida, M.P., Pereira, E. and West, P., 2017. A direct comparison of experimental methods to measure dimensions of synthetic nanoparticles. Ultramicroscopy, 182, pp.179-190.
28. Gillella, S., Divyanjali, M., Rishitha, S., Amzad, S.K., Reddy, U., Girish, C. and Apparao, C.H., 2024. Polymeric nanoparticles–a review. Journal of Innovations in Applied Pharmaceutical Science (JIAPS), pp.25-31.
29. Gujral, G., Kapoor, D. and Jaimini, M., 2018. An updated review on design of experiment (DOE) in pharmaceuticals. Journal of Drug Delivery and Therapeutics, 8(3), pp.147-152.
30. Bhardwaj, H. and Jangde, R.K., 2023. Current updated review on preparation of polymeric nanoparticles for drug delivery and biomedical applications. Next Nanotechnology, 2, p.100013.