Mewar University. Gangrar, Chittorgarh, Rajasthan-312901.
Background: The advancement of drug delivery technologies has been significantly influenced by the development of polymers, which enable controlled release of therapeutic agents. Polymer-based nanoemulsions are emerging as a promising approach for treating psychiatric disorders, particularly with drugs like fluvoxamine. Objective: This study aims to formulate and evaluate the in vitro performance of polymer-based fluvoxamine nanoemulsions, focusing on their drug release profiles, cellular uptake, and cytotoxicity. Approach: The research involved the formulation of fluvoxamine nanoemulsions using various polymers. In vitro evaluations were conducted to assess the controlled drug release, cellular uptake efficiency, and cytotoxic effects on target cells. The study also explored the potential of these nanoemulsions to enhance drug absorption and avoid aggregation. Results: The findings demonstrated that polymer-based fluvoxamine nanoemulsions exhibited a controlled drug release profile, improved cellular uptake, and reduced cytotoxicity compared to conventional formulations. These results indicate a significant advancement in the safety and efficacy of fluvoxamine delivery systems. Conclusion: The study concludes that polymer-based nanoemulsions represent a transformative approach for fluvoxamine delivery, with the potential for further development in clinical applications. The ability of these formulations to enhance drug absorption and provide customizable release profiles suggests a promising future for polymer-based therapeutics in psychiatric disorder treatment.
Fluvoxamine is a selective serotonin reuptake inhibitor that is commonly prescribed for the management of a range of psychiatric disorders, such as obsessive-compulsive disorder, depression and anxiety. Pointing to its crucial role in the management of these debilitating conditions. Nonetheless, the effectiveness of fluvoxamine and such medications is largely limited by the disadvantages of conventional drug delivery systems including low bioavailability, significant first-pass metabolism and unwanted adverse effects. And requires new methods to improve its therapeutic capacity (Stokes & Holtz, 1997). Nanoemulsions or isotropic lipoid dispersions of two immiscible liquids stabilized by surfactants are promising drug delivery systems. Nanocarrier systems have been developed to circumvent the limitations and include advantages such as increased surface area, improved drug solubility, and stability. These advantages of nanoemulsions such as their capacity to solubilize both hydrophilic and hydrophobic drugs make them effective candidates for routes of delivery (Rajpoot et al., 2011), which may include oral, topical, or intravenous routes. In addition, the nanosized droplets can increase the penetration and absorption of drugs, resulting in an improved bioavailability and therapeutic activity (Rajpoot et al, 2011). Polymers are key components in stabilizing nanoemulsions, inhibiting the coalescence of droplets, and controlling the drug release process, which leads to improved overall pain management. Fernandez-Fernandez et al., 2023 emphasized the importance of choosing suitable polymers for stabilizing nanoemulsions to significantly improve their biocompatibility and therapeutic efficacy. Natural and synthetic polymers have been explored to stabilize the nanoemulsions and control drug release. Therefore, the selection of a proper polymer is crucial in developing drug delivery systems in which multifunctional nanocarriers are capable of targeted and controlled release of therapeutics to diseased tissues and this makes the use of polymers necessary in diagnostic or therapeutic approaches. This review will address the formulation strategies for fluvoxamine nanoemulsions, in addition to investigating the in vitro behaviour of polymer-based nanoemulsions, investigating their ability to promote drug delivery and therapeutic efficacy to enhance patient outcomes.
A comprehensive formulation itinerary of fluvoxamine nanoemulsions requires careful selection of the oil phase, surfactants, co-surfactants, and polymers to develop stable, efficacious, and user-friendly formulations. The oil phase generally includes biocompatible oils (i.e., medium-chain triglycerides, vegetable oils, or mineral oils) to solubilize the drug and form an appropriate microenvironment for drug encapsulation. Surfactants such as polysorbates and sorbitan esters are essential as non-ionic interfacial acting molecules that reduce interfacial tension and stabilise the nanoemulsion droplets to avoid coalescence. Other agents known as co-surfactants (e.g., alcohols or glycols) can also stabilize systems by decreasing interfacial tension and augmenting the surfactant film flexibility (reducing droplet diameters) (Dons?? et al., 2011).
Figure 1: Nanoemulsion Formulation and Application
Polymers used in nanoemulsions also contribute to stability and provide for controlled drug release and targetability. The polymers are chosen based on properties such as biocompatibility, biodegradability, and interaction with the drug and other nanoemulsion components. Nanoemulsions are prepared using different techniques – broadly categorized as high-energy and low-energy methods. High-energy techniques (including ultrasonication and microfluidization) use mechanical energy to “break” the oil and water phases into small droplets. Low energy methods based on thermodynamic principles, such as phase inversion and spontaneous emulsification, require limited energy to generate nanoemulsions in the most suited manner depend on droplet size, stability, and production scale. To systematically study the influence of formulation variables on the properties of the nanoemulsions, optimization methodologies such as design of experiments and response surface methodology are employed. These methods provide an approach to discovering ideal parameters, resulting in nanoemulsions with small particle size, low polydispersity index, and high drug encapsulation efficiency. The characterization of nanoemulsions includes measurement of their physicochemical properties such as particle size, polydispersity index and zeta potential, important parameters to predict the stability and in vivo performance of emulsions.
Table 1: Components Used in Fluvoxamine Nanoemulsion Formulation
|
Component |
Examples |
Role |
|
Oil Phase |
Medium-chain triglycerides, vegetable oils |
Solubilizes the drug, forms microenvironment for encapsulation |
|
Surfactants |
Polysorbates, sorbitan esters |
Reduces interfacial tension, stabilizes nanoemulsion droplets |
|
Co-surfactants |
Ethanol, propylene glycol |
Enhances surfactant film flexibility, reduces droplet size |
|
Polymers |
Chitosan, PLGA, PCL |
Stabilizes droplets, controls drug release, enhances biocompatibility |
Table 2: Comparison of High-Energy and Low-Energy Methods for Nanoemulsion Preparation
|
Method |
Technique |
Advantages |
Limitations |
|
High-Energy Methods |
Ultrasonication, Microfluidization |
Small droplet size, high stability |
High energy consumption, expensive equipment |
|
Low-Energy Methods |
Phase inversion, Spontaneous emulsification |
Low energy consumption, cost-effective |
Limited control over droplet size distribution |
Polymers are promising for stabilizing fluvoxamine nanoemulsions and regulating drug release. Natural polymers (chitosan, alginate, etc.) or synthetic polymers (PLGA, PCL, etc.) are some of the types of materials that can be used for this purpose (Raichur et al. 2013). Natural polymers have advantages due to their biocompatibility and biodegradability, while synthetic polymers allow tunable degradation rates and mechanical properties which lead to more controlled drug release profiles. Polymers that hinder the coalescence of droplets or Ostwald ripening are an example of stabilization mechanisms that improve drug encapsulation and control release (Sharma & Singh, 2011) (Raichur et al., 2013) (Zare et al., 2021) (Chime et al., 2019). Polymers create a physical barrier around-the-droplets to prevent them from aggregating and they also decrease the interfacial tension between the droplets and the continuous phase to hinder further droplets from "merging" into other droplets and thus reduce the tendency of droplets to combine and grow in size, a process described as Ostwald ripening. A careful selection of polymer is crucial here because it can be engineered to degrade over time (for sustained drug elution) or respond to pH stimuli to release drug upon exterior signal.[6] Polymers, when included in nanoemulsions, provide several advantages including increased stability, controlled drug release and improved biocompatibility. Efficient Targeting of Drug Delivery through Fluvoxamine Based Nanoemulsions by Using Appropriate Polymers and Formulation TechniquesThe potential classes involved in altering nanoformulation to enhance fluvoxamine therapy include surfactants, polymers and organic solvents (Sharma & Singh, 2011) (Raichur et al., 2013) (Zare et al., 2021) (Chime et al., 2019). The use of nanocarriers (including nanoemulsions) can reduce drug side effects, increase their therapeutic effectiveness, and enhance targeting (Zare et al., 2021). Various mechanisms can be used to control drug release from carrier systems, polymers being an opportunity where the release rate can be fine-tuned (Zare et al., 2021). The use of lipid excipients in nanoformulations facilitates drug formation and enhances drug stability through the protection of the drug in a lipid core (Chime et al., 2019). The use of polymeric nanocarriers may enhance bioavailability, pharmacokinetics, and the efficiency of therapeutic or contrast agents (Karabasz et al., 2020). This biocompatibility of polymers is particularly beneficial for drug delivery systems, providing controlled drug release and stabilization of the molecules, leading to less frequent dosing and longer therapeutic effects (Choukaife et al., 2020). The interaction of living cells with nanoparticles and specific routes for administration, clearance, and the toxic effects are determined by the type, physiochemical properties, and morphology of nanoparticles (Choukaife et al., 2020). Functional excipients as drug delivery system may include polymers for localized delivery and sustained release, drug stabilization, reduction in side effects and increase patient compliance (Jerbi?, 2018) (Choukaife et al., 2020).
Table 3: Types of Polymers Used in Fluvoxamine Nanoemulsions
|
Polymer Type |
Examples |
Properties |
Role in Nanoemulsions |
|
Natural Polymers |
Chitosan, Alginate |
Biocompatible, biodegradable |
Stabilization, controlled release |
|
Synthetic Polymers |
PLGA, PCL |
Tunable degradation rates, mechanical properties |
Controlled release, targeted delivery |
Figure 2: In Vitro Drug Release of Nanoemulsion
Thus, analyzing the in vitro performance of polymeric fluvoxamine nanoemulsions is critical to fully characterize their drug release kinetics, cytotoxicity, and cellular uptake. Drug release studies provide the rate and extent of release of the fluvoxamine from the nanoemulsion, thus confirming the controlled release properties provided by using the uses of the polymers. These studies aid in understanding how the polymer based constituents of the nanoemulsion can affect the release profile of the encapsulated drug. Cytotoxicity assays (MTT, cell survival) test biocompatibility of the nanoemulsion through the evaluation of the nanoemulsion effect on cell survival and proliferation. These assays guarantee that components of the nanoemulsion, such as the polymers, do not induce unwanted cytotoxic activity with target cells. Depending on the application, the characterization study may also encompass cellular uptake studies performed by confocal microscopy or flow cytometry to show the internalization of the nanoemulsion(s) into the target cells and to give useful information on the potential to deliver the drug intracytoplasmically, for instance, fluvoxamine. These studies assess how effectively the nanoemulsion transports the drug into cells, an important factor in its therapeutic effect. Systematic in vitro studies, involving drug release kinetics, cytotoxicity, and cellular uptake measurements, are necessary to guarantee congruence of the therapeutic effect and fluvoxamine nanoemulsions safety. Such extensive in vitro studies give insights into the performance and safety of the polymer-based fluvoxamine nanoemulsions, which ultimately could lead to their clinical translation. Nanomedicine uses nanoparticles to improve bioavailability, pharmacokinetics and the efficiency of therapeutics and contrast agents (Karabasz et al., 2020). Multifunctional nanocarriers improve delivery and permit the controlled, sequential release of multiple therapeutics to diseased tissue that is guided by the unique chemical and biological properties of the polymers used to synthesize these nanocarriers (Karabasz et al., 2020). Polymeric nanoparticles used to reduce side effects and increase therapeutic effects (Thakur et al., 2017). The significant benefit of polymeric nanotherapies in oncology demonstrate a clear proof of concepts from advances in nanomedicine technologies (Thakur et al., 2017) (Karabasz et al., 2020) (Thakur et al., 2017) (Karabasz et al., 2020) (Karabasz et al., 2020).
Table 4: In Vitro Evaluation Parameters for Polymer-Based Fluvoxamine Nanoemulsions
|
Parameter |
Method/Technique |
Purpose |
|
Particle Size |
Dynamic Light Scattering (DLS) |
Determines droplet size and uniformity |
|
Polydispersity Index (PDI) |
DLS |
Assesses size distribution of droplets |
|
Zeta Potential |
Electrophoretic Light Scattering |
Evaluates stability of nanoemulsion |
|
Drug Release |
Dialysis membrane, Franz diffusion cell |
Measures rate and extent of drug release |
|
Cytotoxicity |
MTT assay, Cell viability assays |
Assesses biocompatibility and safety of nanoemulsion |
|
Cellular Uptake |
Confocal microscopy, Flow cytometry |
Evaluates internalization of nanoemulsion into target cells |
5.1. Formulation and Scale-Up Challenges
Despite of these promising possibilities, however, there are several challenges that need to be overcome before polymer-based fluvoxamine nanoemulsions can be effectively utilized. Polymer and surfactant–co-surfactant selection and optimization, therefore, poses substantial formulation challenges to obtaining stable nanoemulsions for certain drug release profiles. A good and effective nanoemulsion system requires a great coordination of physicochemical properties of the oil, surfactant, cosurfactant and water, hence optimization of the above-mentioned components is essential. Scaling up production also poses additional challenges in maintaining the quality and reproducibility of nanoemulsions from laboratory to industry scale methods. Hence the equipment design, process parameters and batch-to-batch variability is to be duly considered and controlled for reproducible production of the polymer based fluvoxamine nanoemulsions.
5.2 Regulatory Considerations
Regulatory criteria for clinical use of nanoemulsions entail the fulfillment of strict quality control standards, safety and efficacy of nanoemulsions. Regulatory approval of the clinical use of such polymer-based nanoemulsions will require detailed characterization as well as extensive in vitro and in vivo evaluation with compliance to good manufacturing practices.
5.3. Future Directions
Further investigations include designing new polymers for improved biocompatibility and biodegradability, employing target delivery mechanisms, and performing detailed in vivo analyses of the therapeutic capacities and safety of the formulations of fluvoxamine nanoemulsions. Encapsulation of fluvoxamine in such intelligent stimuli-responsive polymers may help improve both the controlled release and site-specific delivery of the drug, which may further help in getting better therapeutic outcomes. Further studies including long-term stability testing, in vivo efficacy and toxicological assessments are needed to advance polymer-based fluvoxamine nanoemulsions for clinical application. In-depth evaluations are essential to identify any concerns and ensure the successful clinical implementation of these innovative drug delivery systems. By fulfilling particular requirements for all kinds of systems, polymers can improve the design of drug delivery systems (Begines et al., 2020). The tunable biodegradability, biocompatibility and stimuli responsiveness of these materials are important for improving drug administration. These properties have permitted the development of delivery strategies that provide controlled drug release, target specific tissues, and protect drugs from extreme biological environments, thereby enhancing therapeutic efficacy and safety. Polymers are fundamental for developing new drug delivery technologies due to their ability to tailor drug release kinetics, increase drug stability, and enhance biocompatibility.
Polymers have the potential of boosting therapy for neuropsychiatric disorders specifically fluvoxamine nanoemulsions. These new drug delivery systems overcome the limitations of traditional fluvoxamines formulations and enhance drug solubility, stability, and bioavailability (Choukaife et al., 2020). By strategically integrating polymers in nanoemulsions, controlled drug release, efficient drug encapsulation, and organ targeting can be achieved, leading to improved therapeutic efficacy. Polymer-based fluvoxamine nanoemulsions were shown in vitro to afford controlled drug release profile, enhanced cellular uptake, and lower cytotoxicity. These extensive studies lead to general understanding in performance as well as safety of the polymer-based fluvoxamine nanoemulsions and suggests their further development for clinical application. Further investigations should endeavor to tackle research challenges to advance novel paths towards a successful nanoemulsion formulation and clinical translation of the pathway. In-depth knowledge on various aspects like formulation optimization, scale-up, and regulatory considerations are critical in the development of these polymer-based nanoemulsions.
Development of polymer based nanoemulsions could revolutionize drug delivery and personalized medicine —especially for those living with psychiatric disorders (Karabasz et al., 2020) (Begines et al., 2020). Polymers as drug delivery systems are useful as they can localize drug distribution, maintain drug stability and minimize toxicity (Jerbi?, 2018)(Liechty et al., 2010). Furthermore, the polymers in nanoemulsions can avoid drug aggregation, enhance drug absorption, and provide customizable release profiles (Liechty et al., 2010) (Jerbi?, 2018). The development of polymers has significantly bolstered drug delivery technology by allowing the controlled delivery of therapeutic agents over time through sustained, cyclic or tunable release of hydrophilic and hydrophobic drugs (Liechty et al., 2010). However, advances in polymer-based nanoemulsions represent an exciting and potentially transformative approach for psychiatric disorder therapeutics. Nanoparticles are investigated for biomedical applications because of their unique properties such as small size, easy surface alteration, additional solubility, and multifunctionality (Choukaife et al., 2020). Polymeric nanocarriers are an example of multifunctional systems that have shown potential in improving the bioavailability and pharmacokinetics of several therapeutics (Karabasz et al., 2020). This will support further exploration of alternative polymer development, methods of targeted delivery, and in vivo evaluation for therapeutic utility and safety of fluvoxamine nanoemulsions.
Consent for Publication
Not Applicable
Conflicts of Interest
The authors declare that there are no conflicts of interest, whether financial or otherwise.
ACKNOWLEDGEMENTS
The author is sincerely grateful to MD. ZULPHIKAR ALI, ASSITANT PROFESSOR, Department of pharmacy, Mewar University, Chittorgarh, Rajasthan for constant support and guidance during the review. He offered such thoughtful commentary and support, without which this work would not be possible. Also shall the author thank Mewar University to provide its opportunity and resources which greatly helped in completing this project.
REFERENCES
Obed Mihriemate*, Md. Zulphikar Ali, Review On Formulation and In Vitro Evaluation of Polymer-Based Fluvoxamine Nanoemulsion, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 3, 2625-2632. https://doi.org/10.5281/zenodo.15091477
10.5281/zenodo.15091477
