Advanced-Transdermal-Drug-Delivery-Systems (1).pptx

Transdemal drug delivery systems

1. FOOTER Smt. N.M Padalia Pharmacy College, Ahmedabad To be presented at… National Seminar on “Advances in Transdermal Drug Delivery : Formulation Insights and Future Pathways” Presented by Dev N. Suthar Sem-5 Smt. N.M Padalia Pharmacy College.

2. Transdermal Delivery of Biologics : BREAKING THE SIZE BARRIER

3. Skin Barrier & Challenges Stratum Corneum Barrier The stratum corneum is the main permeability barrier—only small, lipophilic drugs (<500 Da) cross easily. Modern Therapeutic Challenges Modern therapeutics (proteins, peptides, vaccines) face poor skin permeation due to large molecular weight and hydrophilicity. Key Challenge Achieve high drug flux without damaging skin integrity. Focus Area Enhancing transdermal permeability via physical, chemical, and nanotechnological approaches.

4. Why Transdermal Delivery for Biologics? Avoids First-Pass Metabolism Avoids first-pass metabolism and enzymatic degradation in GI tract. Sustained & Controlled Release Enables sustained and controlled release for better patient compliance. Ideal for Chronic Diseases Ideal for chronic diseases (diabetes, hormonal deficiencies, autoimmune disorders). Reduces Needle-Associated Risks Reduces needle-associated infections and fear of injections. Self-Administration Potential Potential for self-administration and long-term therapy with minimal side effects.

5. Barriers Beyond Stratum Corneum Epidermal enzymes may degrade peptide-based biologics Hydrophilicity & large size hinder lipid bilayer diffusion Protein instability due to denaturation, aggregation, or oxidation Diffusion resistance in viable epidermis and dermis layers Overcoming these requires biochemical and biophysical intervention

6. 💡 Strategies to Break the Size Barrier Microneedle-assisted delivery creates microchannels without pain Chemical enhancers transiently alter lipid structure (fatty acids, terpenes) Electroporation uses short electrical pulses to open aqueous pores Iontophoresis electrical current drives charged macromolecules Sonophoresis (Ultrasound) acoustic energy enhances permeability Nanocarrier systems encapsulate biologics for deep skin transport Key Insight: Combine multiple methods to enhance diffusion safely and reversibly.

7. 🔬 Microneedle Systems for Biologics 1 Types Solid microneedles Coated microneedles Hollow microneedles Dissolving microneedles Hydrogel-forming microneedles 2 Mechanism Create microscopic pores (~50–200 µm) for direct entry of large molecules 3 Applications Insulin microneedle patches (painless diabetes therapy) DNA/RNA vaccine delivery (COVID-19, HPV) Delivery of monoclonal antibodies & peptides 4 Recent innovations 3D-printed and self-dissolving microneedles with controlled kinetics 5 Impact Converts biologics into "injectable-like" patches

8. 🧫 Nanocarrier-Based Systems Liposomes, Transfersomes, and Ethosomes Flexible lipid vesicles that deform and pass through intercellular gaps Polymeric nanoparticles Provide sustained release and protect biologics from degradation Lipid-polymer hybrid nanoparticles Combine stability + biocompatibility Nanoemulsions and dendrimers Increase solubility and bioavailability of hydrophilic peptides Cell-penetrating peptide (CPP)-linked nanocarriers Enhance intracellular delivery to target cells Outcome: Deep dermal penetration without structural loss of biologics

9. 🧠 Stabilizing Biologics in TDDS Issue: Biologic Instability Proteins and peptides are unstable under mechanical stress or heat. Stabilizers Utilized Sugars (trehalose), amino acids, and polymers (PEG) are commonly used. Encapsulation Strategies Lipid or polymeric carriers shield biologics from degradation. Lyophilized Microneedles Preserve biologic activity until contact with skin moisture. Temperature-Sensitive Storage Patches designed for ambient stability—no cold chain needed. Overarching Goal Maintain biologic integrity throughout the delivery process.

10. 🌍 Current Clinical Progress Transdermal interferon & erythropoietin in preclinical development COVID-19 mRNA microneedle patch promising animal trial results (UNC Chapel Hill) Etanercept & Adalimumab transdermal systems research on arthritis management Influenza DNA vaccine patches Phase I studies show immune response comparable to injection Insulin microneedle patches under human trials (MIT, Rani Therapeutics) Trend: Transition from proof-of-concept → clinical validation stage

11. 🔮 Future Pathways AI-driven TDDS Predict optimal delivery parameters for specific biologics 3D printed microneedles On-demand, patient-personalized patches Bio-responsive polymers Trigger release in response to skin pH or glucose levels Wearable "smart patches" Monitor biomarkers + auto-adjust biologic release Next frontier Transdermal gene therapy and RNA-based therapeutics Vision Replace needles with intelligent, self-regulating, skin-based delivery systems

12. ⚗️ Generational Evolution of TDDS Generation Mechanism Advancement 1st Gen Passive diffusion through intact skin Limited to low MW lipophilic drugs 2nd Gen Controlled enhancement via iontophoresis, sonophoresis Increased drug penetration 3rd Gen Active, targeted, smart delivery (microneedles, nanocarriers) Enables biologic delivery and personalisation Key insight: The future lies in active and intelligent systems, not passive patches.

13. 🧪 Advanced Formulation Components 01 Polymeric Matrix Controls release kinetics (EVA, PVP, HPMC). 02 Permeation Enhancers Terpenes, surfactants, and fatty acids disrupt lipid packing. 03 Pressure-Sensitive Adhesives Provide intimate skin contact while allowing breathability. 04 Backing Membrane Prevents drug loss and ensures occlusion. 05 Rate-Controlling Layer Governs diffusion and prolongs steady-state release. Formulation science = balancing diffusion, stability, and skin comfort.

14. 🧫 Nanotechnology in TDDS Liposomes & Niosomes Improve solubility and localise drugs in deeper epidermis. Transfersomes & Ethosomes Ultradeformable vesicles that squeeze through tight skin junctions. Solid Lipid Nanoparticles (SLN) Offer sustained release and protect labile drugs. Nanostructured Lipid Carriers (NLC) Second-generation SLNs with higher drug loading and stability. Nanoemulsions Enhance transdermal delivery of both hydrophilic and lipophilic agents. Nanocarriers = skin-targeted precision vehicles.

15. 🩹 Microneedle Technology Create microchannels (~50–200 μm deep) bypassing stratum corneum without pain. Types: Solid, coated, hollow, dissolving, and hydrogel-forming microneedles. Materials: Biodegradable polymers, silicon, metals. Enable delivery of biologics, vaccines, and hormones painlessly. Example: Dissolving insulin microneedle patches for diabetic therapy. Microneedles = bridge between injection and transdermal patch.

16. ⚡ Physical Enhancement Techniques Iontophoresis Low electric current drives charged drugs across skin. Sonophoresis (Ultrasound) Increases skin porosity via cavitation. Electroporation Short electrical pulses create transient pores. Magnetophoresis Magnetic fields enhance drug movement across skin. Combination Systems Integrate two or more methods for high-molecular-weight drug delivery. Energy-based TDDS = precision-controlled permeability.

17. 🧠 Smart and Responsive Systems Thermo-responsive Polymers Release drugs on temperature increase (e.g., fever patches). pH-sensitive Carriers Trigger release in inflamed or infected skin. Glucose-responsive Microneedles Adjust insulin release automatically. AI-integrated Wearables Monitor parameters like hydration, temperature, and drug level for real-time dose control. Next-gen TDDS = adaptive, patient-centric, data-driven therapy.

18. 🧩 Biologics & Macromolecule Delivery Conventional patches fail for large hydrophilic molecules like proteins. Emerging Strategies: Microneedle-assisted Delivery For insulin, vaccines. Cell-penetrating Peptides (CPPs) To facilitate intracellular transport. Nanocarriers with Lipid–Polymer Hybrids For dual permeability and stability. Outcome: Non-invasive biologic delivery comparable to injections. Goal: Replace painful injections with smart transdermal systems.

19. 🔬 Evaluation Techniques In vitro skin permeation: Franz diffusion cells using human/animal skin. Ex vivo studies: Assess barrier disruption and recovery. In vivo evaluation: Pharmacokinetics and bioavailability in animal/human models. Mechanical & Adhesion Testing: Ensures flexibility, tack, and durability. Stability studies: Evaluate chemical integrity and drug crystallisation. Validation = translation from lab success to clinical reliability.

20. THANK YOU.