Can Tiny Treatments Make a Big Difference for Children? The Promise of Nanomedicine

Abstract

Nanomedicine promises to change the face of therapeutics and diagnostics, combining enhanced drug delivery, improved bioavailability, and targeted action. Although advances have been realized in adult nanomedicine, pediatrics still lags in application. Simple adjustments in dose based on weight or surface area are too inadequate for unique pediatric physiology and developmental stages; specific formulations would be required. This review focuses attention on the most critical physiological differences between children and adults that will affect the drug ADMET, presents pediatric diseases suited for nanomedicine intervention, details formulation approaches used in marketed pediatric nanomedicines-which include liposomes, nanocrystals, polymeric nanoparticles, and lipid nanoemulsions-and lastly discusses challenges, gaps, and prospects of this promising field.

Introduction

Nanomedicine, an application of nanotechnology to medicine, has emerged as a powerful platform for improving drug delivery, enhancing therapeutic efficacy, and enabling advanced diagnostics. Manipulation of materials at the nanoscale (1-100 nanometers) allows nanomedicine to offer unique advantages such as increased drug payload, enhanced stability, controlled drug release profiles, improved bioavailability, and targeted drug delivery to specific tissues or cells. These properties make the compounds particularly relevant in pediatrics, where precise drug delivery and minimized off-target effects are crucial for optimal treatment outcomes.

Although there has been vast progress in developing and clinically translating nanomedicines for adult populations, in pediatrics it has been slower. This can be attributed to the vast differences in physiology that exist between a child and an adult, where these differences highly affect the drug ADMET. Hence, pediatric nanomedicines are developed with specificity rather than just extrapolation from adults. To address this knowledge gap, the review focuses on the critical physiological differences between children and adults that affect the drug ADMET, revealing pediatric diseases amenable to nanomedicine intervention, formulation approaches used in marketed pediatric nanomedicines, challenges, existing gaps, and prospects of this vital field.

Literature Review

The literature on nanomedicine is vast, but focused pediatric research is more limited. Key areas of existing research include:

• Physiological differences and ADMET in pediatrics: Studies have characterized the age-related changes in gastric pH, gastrointestinal motility, organ size, and function (liver, kidneys), body composition, and blood-brain barrier permeability, all of which influence drug pharmacokinetics.

• Nanomedicine formulations and characterization: Research has explored various nanomaterials (lipids, polymers, metals) and fabrication techniques for drug delivery, focusing on biocompatibility, biodegradability, and targeting capabilities.

• Preclinical studies of nanomedicine in pediatric disease models: Studies have evaluated the efficacy and safety of nanomedicines in animal models of pediatric diseases such as cancer, infections, and genetic disorders.

• Limited clinical trials of nanomedicine in children: While the number is growing, clinical trials of nanomedicines specifically designed for or adapted to children are still relatively scarce.

Physiological Differences Between Children and Adults Impacting ADMET

Several key physiological differences between children and adults significantly impact drug ADMET and necessitate careful consideration in nanomedicine development:

• Gastric pH: Gastric pH is higher in neonates and infants, gradually decreasing to adult levels by early childhood. This affects the dissolution and absorption of acid-labile drugs.

• Gastrointestinal Motility: Gastric emptying and intestinal transit times are slower in neonates and infants, affecting drug absorption rates.

• Body Composition: Children have a higher proportion of body water and a lower proportion of body fat compared to adults, affecting the distribution of hydrophilic and lipophilic drugs.

• Organ Maturation: Hepatic and renal function are not fully developed in neonates and infants, impacting drug metabolism and excretion.

• Blood-Brain Barrier: The blood-brain barrier is more permeable in infants, increasing the potential for drug entry into the central nervous system.

• Enzyme Activity: The activity of drug-metabolizing enzymes, such as cytochrome P450 enzymes, varies with age, affecting drug metabolism rates.

Pediatric Diseases as Ideal Candidates for Nanomedicine Intervention

Several pediatric diseases are particularly well-suited for nanomedicine intervention due to the potential for improved drug delivery and therapeutic outcomes:

• Cancer: Nanomedicines can improve targeted delivery of chemotherapy drugs to tumor cells, reducing systemic toxicity.

• Infections: Nanomedicines can enhance the delivery of antibiotics and antiviral drugs to infected tissues, improving treatment efficacy and reducing the development of resistance.

• Genetic Disorders: Nanomedicines can be used for gene therapy and gene editing approaches to correct genetic defects.

• Inflammatory Diseases: Nanomedicines can deliver anti-inflammatory drugs directly to affected tissues, minimizing systemic side effects.

Formulation Approaches in Marketed Pediatric Nanomedicines

Several nanotechnology-based formulations have been successfully translated to clinical use in pediatrics:

• Liposomes: These spherical vesicles composed of lipid bilayers can encapsulate drugs and improve their delivery to target cells.

• Nanocrystals: These nanosized drug particles enhance drug dissolution and bioavailability, particularly for poorly soluble drugs.

• Polymeric Nanoparticles: These particles can encapsulate drugs and provide controlled drug release.

• Lipid Nanoemulsions: These oil-in-water emulsions can improve the delivery of lipophilic drugs.

Challenges and Gaps in Pediatric Nanomedicine Development and Commercialization

Several challenges and gaps hinder the development and commercialization of pediatric nanomedicines:

• Limited pediatric-specific preclinical models: Developing appropriate animal models that accurately reflect pediatric physiology and disease is crucial.

• Ethical considerations in pediatric clinical trials: Conducting clinical trials in children requires careful consideration of ethical issues related to informed consent and minimizing risks.

• Regulatory hurdles: Regulatory pathways for pediatric nanomedicines need to be clarified and streamlined.

• Lack of funding for pediatric nanomedicine research: Increased funding is needed to support research and development in this important area.

Future Perspectives

The future of pediatric nanomedicine is promising, with ongoing research and development focused on:

• Developing more targeted and responsive nanomedicines.

• Improving the safety and biocompatibility of nanomaterials.

• Developing new diagnostic nanotechnologies for early disease detection.

• Establishing standardized protocols for the development and clinical translation of pediatric nanomedicines.

Conclusion

Nanomedicine will have tremendous scope in pediatric health care in offering more effective targeted therapies for diseases. Addressing unique physiological features in children and the challenges faced by nanomedicines in terms of development and commercialization is critical for its realization and the improvement in the lives of children worldwide.