Pharmacogenomics and transdermal drug delivery: Innovations in phamas scine and biomedile

Cheng Wei

doi:10.35841/aabps-15.111.300

Editorial - Asian Journal of Biomedical and Pharmaceutical Sciences (2025) Volume 15, Issue 11

Pharmacogenomics and transdermal drug delivery: Innovations in phamas scine and biomedile

Cheng Wei^*

Department of Molecular Pharmacology, Tsinghua University, China

*Corresponding Author:: Cheng Wei
Department of Molecular Pharmacology
Tsinghua University, China
E-mail: chengwei@tsinghua.edu.cn

Received: 01-May -2025, Manuscript No. AABPS-25 -166496; Editor assigned: 03-May-2025, Pre QC No. AABPS-25-166496(PQ); Reviewed: 17-May-2025, QC No.AABPS-24-166496; Revised: 21-May-2025, Manuscript No. AABPS-25-166496(R); Published: 28-May-2025, DOI: 10.35841/aabps-15.111.300

Citation: Wei C. Pharmacogenomics and transdermal drug delivery: Innovations in phamas scine and biomedile. Asian J Biomed Pharm Sci.2025;15(111):300

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Introduction

Pharmacogenomics and transdermal drug delivery represent two rapidly evolving domains within phamas scine and biomedile, converging to enhance personalized therapeutics. Pharmacogenomics examines how genetic variations influence individual drug responses—informing optimal dosing, minimizing adverse effects, and maximizing therapeutic efficacy. Transdermal drug delivery (TDD), meanwhile, bypasses gastrointestinal limitations by administering medications across the skin, providing sustained release, improved patient compliance, and reduced systemic toxicity. When integrated, pharmacogenomic insights guide the selection and design of transdermal systems tailored to genetic profiles, ensuring precise, individualized therapy [1].

Genetic polymorphisms in CYP enzymes—such as CYP2D6, CYP3A4, and CYP2C9—profoundly affect drug metabolism. For instance, CYP2D6 poor metabolizers may accumulate active metabolites of analgesics, increasing the risk of toxicity, whereas ultra-rapid metabolizers may fail to achieve therapeutic concentrations. Variants in ATP-binding cassette (ABC) transporters (e.g., ABCB1) alter drug efflux from cells. In TDD, understanding polymorphisms in skin-expressed transporters informs permeation kinetics and systemic absorption profiles. Pharmacogenomic profiling of drug targets—such as VKORC1 for warfarin or the μ-opioid receptor (OPRM1) for analgesics—enables clinicians to predict responsiveness and adverse event risk before initiating therapy. By integrating genotypic data—obtained via PCR-based assays or next-generation sequencing—clinicians can stratify patients into metabolizer phenotypes (poor, intermediate, extensive, ultra-rapid). This stratification guides drug selection, dosage adjustments, and monitoring protocols [2].

Transdermal systems (patches, gels, microneedle arrays) enable continuous drug release over hours to days, maintaining steady plasma concentrations. This mitigates peak-trough fluctuations common with oral or injectable routes—particularly beneficial for drugs with narrow therapeutic indices and subject to genetic variability in metabolism. Drugs administered transdermally avoid gastrointestinal degradation and hepatic first-pass effects. For patients with genotypes predicting reduced hepatic clearance (e.g., CYP2C19 poor metabolizers), TDD prevents excessive accumulation of metabolites, lowering the risk of hepatotoxicity. Patch-based therapies reduce dosing frequency. In chronic conditions—such as pain management, hormone replacement, or smoking cessation—fixed transdermal regimens accommodate genotypic subgroups requiring lower or higher daily drug exposures, as determined by pharmacogenomic profiling. By localizing drug delivery to dermal capillaries, TDD systems can minimize off-target distribution. For example, transdermal nicotine or clonidine patches reduce gastrointestinal and central nervous system side effects compared to oral formulations—especially relevant for individuals with genetic susceptibilities to adverse reactions [3].

Patch matrices can be engineered with variable drug loading densities. Patients identified as CYP2D6 ultra-rapid metabolizers may receive a higher loaded patch to compensate for rapid clearance, while poor metabolizers receive lower drug-load versions. Solid or dissolvable microneedle arrays can be configured with differing needle lengths and densities to modulate flux rates. Genetic profiling informs the proper array configuration to achieve target plasma levels Transdermal formulations may include pro-permeation peptides cleaved by polymorphic skin peptidases. For subjects with high enzyme activity, a lower concentration of enhancer ensures controlled permeation; conversely, low-activity phenotypes receive formulations with higher enhancer content to achieve adequate flux [4].

Certain transdermal vesicular systems incorporate peptides or small molecules that engage skin receptors to facilitate endocytosis. Pharmacogenomic data on receptor expression variability (e.g., α1-adrenergic receptors in keratinocytes) inform ligand selection and concentration. Advanced PBPK-TDD models integrate genetic variability parameters—such as enzyme kinetics (V_max, K_m), transporter expression levels, and skin permeability coefficients—to predict drug concentration–time profiles. Iterative simulations guide formulation refinement before clinical validation, streamlining development. Fentanyl predominantly undergoes CYP3A4-mediated metabolism; morphine’s M6G/ M3G formation involves UGT2B7. Patients with CYP3A4*22 or CYP2D6 poor-metabolizer alleles require dose modifications to prevent under- or over-dosing [5].

A pharmacogenomic panel identifies patients likely to accumulate high active metabolite levels, prompting initiation with lower-strength patches. Conversely, ultra-rapid metabolizers receive higher transdermal flux designs to maintain analgesia. Polymorphisms in CYP1A2 and CYP3A4 affect estradiol clearance. Transdermal estradiol avoids extensive first-pass metabolism; however, genotype-driven adjustments in patch area ensure consistent systemic levels. Variants in estrogen receptor α (ESR1) influence local skin reservoir formation, affecting systemic release dynamics. Genetic screening informs selection between matrix versus reservoir patches. CYP2A6 polymorphisms determine nicotine clearance rates. Poor metabolizers experience prolonged half-life, requiring a lower transdermal dose to avoid toxicity, whereas rapid metabolizers may need higher-strength patches [6].

Combined with genetic counseling, personalized patch regimens improve cessation rates by aligning transdermal nicotine delivery with individual metabolic phenotypes. Skin expresses metabolic enzymes (e.g., CYP1B1, CYP2E1) at variable levels across genotypes and anatomical sites, complicating prediction of local drug activation or deactivation.Genetic variability exists alongside factors like age, skin hydration, and comorbidities (e.g., diabetes affecting skin vasculature). Implementing genotype-driven TDD requires comprehensive patient assessment and education to ensure adherence. Current regulations for TDD systems do not uniformly address pharmacogenomic considerations. Standardized guidelines for integrating genetic data into labeling and dosage recommendations are needed [7].

Embedded biosensors monitor biomarkers (e.g., drug plasma levels, skin impedance) and adjust transdermal flux via microcontroller-driven actuators—enabling real-time, genotype-informed dosing adjustments. Incorporating lipid- or polymer-based nanocarriers—loaded with pharmacogenomically optimized drug concentrations—enhances skin penetration while protecting labile compounds. Genomic data guides nanoparticle surface modifications to target transporter expression in keratinocytes. Mobile platforms store individual pharmacogenomic profiles, cross-reference real-time adherence data, and prompt patients to replace patches or modify usage based on sensor feedback—creating closed-loop TDD systems [8].

Home-based saliva kits for genotyping, coupled with telehealth consultations, accelerate genotype-guided TDD therapy initiation—particularly beneficial in rural or resource-limited settings. Regulatory agencies (e.g., China’s NMPA, FDA) will need to establish criteria for approving transdermal products with genotype-specific labeling. This includes validation of in vitro–in vivo correlations under different genetic backgrounds. Safeguarding patient genetic data—required for pharmacogenomic TDD applications—demands robust privacy standards and integration of genetic counseling services to ensure informed consent and ethical use [9, 10].

Conclusion

Pharmacogenomics and transdermal drug delivery, when combined, offer a powerful paradigm for personalized medicine in phamas scine and biomedile. By leveraging genetic insights—encompassing drug-metabolizing enzymes, transporters, and receptor polymorphisms—clinicians and formulators can design transdermal systems that deliver optimal drug concentrations tailored to individual metabolic profiles. While challenges remain, including skin biotransformation complexity and the need for harmonized regulatory frameworks, ongoing innovations in smart patches, nanocarriers, and digital health integration promise to revolutionize patient-centric therapy. As research advances, pharmacogenomics-guided TDD will play a pivotal role in delivering safer, more effective treatments—fulfilling the promise of truly individualized medicine.