Developing Novel Polymers and Nanomaterial for Transmucosal Naproxen Drug Delivery

Abstract

The development of novel polymers and nanomaterials for transmucoasal drug delivery holds immense promise for enhancing the bioavailability and therapeutic efficacy of various drugs. This study focuses on the design and fabrication of advanced polymeric matrices and nanomaterials for the transmucoasal delivery of naproxen, a widely used nonsteroidal anti-inflammatory drug (NSAID). Transmucoasal delivery systems are advantageous over traditional oral or parenteral routes, as they offer enhanced drug absorption, improved patient compliance, and reduced side effects. In this work, a variety of biocompatible and biodegradable polymers, along with nanomaterial-based carriers such as nanoparticles and nanogels, were synthesized and characterized for their suitability in naproxen delivery. The fabricated systems were evaluated for their mucoadhesive properties, controlled drug release profiles, and in vitro permeation through mucosal barriers. The results demonstrate significant improvements in naproxen absorption and sustained release, suggesting the potential of these novel polymeric and nanomaterial systems for effective transmucoasal drug delivery. These findings provide a foundation for future studies aimed at optimizing transmucoasal drug delivery systems for enhanced therapeutic outcomes.

Introduction

1. Transmucosal Vesicles

Definition & Structure:

• Ultra-deformable vesicles with an aqueous core and a flexible lipid bilayer composed of phospholipids and surfactants (e.g., Sodium Cholate, Tween, Spans).

• Flexible enough to pass through pores 5–10 times smaller than their size and transport drugs effectively.

• Can carry hydrophilic, lipophilic, and amphiphilic drugs.

Mechanism of Action:

• Penetrate intact skin via osmotic gradients and skin hydration (hydrotaxis).

• Disrupt intercellular lipids in the stratum corneum, widening pores for drug delivery.

• Act as depots for sustained release in topical applications and modulate systemic absorption in transdermal delivery.

Applications:

• Deliver low- and high-molecular-weight drugs, including analgesics, corticosteroids, hormones, anticancer drugs, insulin, proteins, and peptides.

• Protect drugs from metabolic degradation.

• Suitable for both systemic and topical drug delivery.

Advantages:

• High entrapment efficiency (~90% for lipophilic drugs).

• Biocompatible and biodegradable.

• Can accommodate diverse drug types and molecular sizes.

• Simple, scalable preparation methods.

Limitations:

• Chemically unstable; prone to oxidative degradation.

• Relatively higher formulation costs.

Preparation Methods:

1. Vortexing-sonication

2. Suspension homogenization

3. Modified handshaking (lipid film hydration)

4. Aqueous lipid suspension

5. Centrifugation

• Thin-film hydration and sonication commonly used to produce small, uniform vesicles.

Characterization Parameters:

• Entrapment efficiency, vesicle size & morphology, zeta potential, polydispersity, penetration ability, occlusion effect, stability, in-vitro drug release.

2. Emulgel for Topical Delivery

Definition:

• Gel containing an emulsion (oil-in-water or water-in-oil), combining benefits of emulsions and gels for topical drug delivery.

Skin Physiology Relevance:

• Enables drug penetration and targeted delivery.

• Bypasses first-pass metabolism.

Types:

• Nanoemulgel: Uses nanoemulsions (1–100 nm) for enhanced permeation and faster therapeutic effect.

• Macroemulgel: Uses larger droplets (>400 nm); thermodynamically unstable but stabilized by surfactants.

Advantages:

• Can incorporate hydrophobic drugs effectively.

• Stable, simple, cost-effective, patient-friendly.

• Avoids sonication and facilitates self-medication.

Disadvantages:

• Possible skin irritation or allergic reactions.

• Some drugs may have poor skin permeability.

• Difficulty in absorbing larger drug particles.

Components:

• Oils (mineral, castor), Vehicles (aqueous or oily), Emulsifiers (Tween 80, Span 80), Gelling agents (Carbopol 940, HPMC), pH adjusters (NaOH, triethylamine).

Preparation Steps:

1. Create gel base (adjust pH 5–6.5).

2. Prepare emulsion (O/W or W/O).

3. Mix emulsion into gel base to form emulgel.

3. Naproxen Drug Profile

• Chemical: (2S)-2-(6-methoxynaphthalen-2-yl)propanoate

• Category: NSAID (Analgesic, anti-inflammatory, antipyretic)

• Molecular Weight: 230.26 g/mol

• Solubility: Slightly soluble in water; soluble in methanol, chloroform, ethanol.

• Mechanism: Inhibits cyclooxygenase → reduces prostaglandin production → lowers pain, inflammation, and fever.

• Pharmacokinetics:

  • Oral bioavailability >80%

  • Plasma protein binding >99%

  • Half-life: 12–17 hours

• Contraindications: Allergy to aspirin/NSAIDs; may interact with anticoagulants, lithium, methotrexate.

4. Excipients Used

1. Carbopol 974: Gel base, bioadhesive, stabilizer.

2. Tween 80: Nonionic surfactant/emulsifier, enhances emulsification and stability.

3. Soy Lecithin: Phospholipid source, forms vesicles for drug delivery.

5. Research Aim & Objectives

Aim:

• Develop and optimize polymers and nanomaterials for efficient transmucosal delivery of naproxen.

Objectives:

• Evaluate drug-excipient compatibility.

• Prepare naproxen transmucosal vesicles using thin-film hydration with Soy PC & Tween 80.

• Characterize vesicles (particle size, zeta potential, entrapment efficiency).

• Formulate optimized gel using Carbopol.

• Perform evaluation tests (drug content, pH, viscosity, spreadability, in-vitro release).

6. Methodology Overview

• Drug identification: Organoleptic tests, melting point.

• Preformulation studies: Calibration curves, solubility, FTIR compatibility.

• Fabrication: Thin-film hydration to prepare naproxen transmucosal vesicles.

• Characterization: Particle size, entrapment efficiency, zeta potential.

• Gel formulation: Incorporate vesicles into Carbopol gel and evaluate physicochemical properties and in-vitro drug release.

Conclusion

From this study, it was concluded that the best formulation of NaproxenTransmucosal, with high EE% and small particle size. Also, the fabrication of Naproxen as Transmucosal has the ability to defeat the barrier properties of the skin and enhance the drug release.

References

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Copyright

Copyright © 2025 Mudiga Anuradha, Dr. Duguta Tirumala, Gangadevi Shirisha, T Surekha. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.