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Route of administration

A route of administration is the method by which a drug or therapeutic agent is delivered into or onto the body to achieve its pharmacological effect, encompassing the pathway that influences absorption, distribution, metabolism, and excretion.^[1] This approach is fundamental in pharmacology, as it determines the drug's bioavailability—the fraction that reaches systemic circulation—and the onset, duration, and intensity of therapeutic action, with common examples including oral ingestion, intravenous injection, and topical application.^[2]^[3] Routes of administration have ancient origins, with oral ingestion and topical applications used by early civilizations such as the Egyptians and Greeks for medicinal purposes. Parenteral routes, particularly intravenous administration, emerged in the 17th century through pioneering experiments by figures like Christopher Wren, who used animal bladders and quills for infusions, and became clinically viable in the 19th century during cholera epidemics for fluid replacement.^[4] Routes of administration are typically classified into three major categories: enteral, parenteral, and topical (or local), each suited to specific clinical needs based on the drug's physicochemical properties and the patient's condition.^[5] Enteral routes involve passage through the gastrointestinal tract, including oral, sublingual or buccal, and rectal administration.^[3]^[5] Parenteral routes bypass the digestive system for faster or more reliable delivery, including intravenous, intramuscular, subcutaneous, and intradermal administration.^[5] Topical routes target localized areas or allow transdermal absorption, such as application to the skin, inhalation, nasal, ocular, or vaginal/rectal administration.^[3]^[5] The selection of an appropriate route is influenced by multiple factors to optimize efficacy while minimizing risks, including the drug's stability, required speed of action, bioavailability challenges, patient-specific considerations, and practical aspects such as convenience and cost.^[2]^[3] Each route carries distinct advantages and potential drawbacks.^[5] Overall, proper route selection enhances therapeutic outcomes and patient safety across medical practice.^[6]

Introduction

Definition and Scope

Routes of administration refer to the specific paths or methods by which therapeutic agents, such as drugs, are introduced into the body to produce desired systemic or localized pharmacological effects.^[1] This concept encompasses the deliberate selection of entry points that facilitate the drug's interaction with target tissues or organs, ensuring optimal therapeutic outcomes while minimizing adverse effects.^[2] The scope of routes of administration is broad, covering a range of techniques from non-invasive methods like ingestion to invasive procedures such as injection, with the choice profoundly influencing key pharmacokinetic parameters including bioavailability, onset of action, and duration of effect.^[7] Broadly, these routes are categorized into enteral (involving the gastrointestinal tract), parenteral (bypassing the gastrointestinal tract), and topical or mucosal (applied to skin or mucous membranes for local or systemic absorption).^[2] Each category allows for tailored drug delivery suited to the medication's properties and the patient's needs, spanning oral tablets, intravenous infusions, transdermal patches, and more.^[8] The importance of selecting an appropriate route lies in its direct impact on drug efficacy, safety, and patient outcomes, as it governs absorption rates—the speed at which the drug enters the bloodstream—and modulates first-pass metabolism, where hepatic enzymes metabolize a portion of the drug before it reaches systemic circulation, potentially reducing bioavailability.^[9] For instance, routes avoiding the gastrointestinal tract can achieve higher bioavailability by circumventing first-pass effects, leading to faster onset and more predictable duration of action, which is critical for conditions requiring rapid intervention or sustained release.^[7] Ultimately, this foundational aspect of pharmacology optimizes therapeutic precision, enhances compliance, and mitigates risks associated with suboptimal delivery.^[10]

Historical Development

The earliest known routes of drug administration date back to ancient civilizations, where oral ingestion and topical applications were predominant methods for delivering herbal remedies and other medicaments. In ancient Egypt, around 1550 BCE, the Ebers Papyrus documented over 700 medicinal formulas, primarily involving oral consumption of plant-based concoctions for treating ailments such as infections and digestive issues, alongside topical applications like ointments and poultices applied directly to the skin.^[11] Similarly, in ancient Greece, Hippocrates (c. 460–377 BCE), often regarded as the father of medicine, advocated for the use of herbal poultices—mixtures of plants such as barley and honey applied externally—to reduce inflammation and promote wound healing, emphasizing natural substances in numerous recorded remedies.^[12] These practices reflected a foundational understanding of drug delivery through simple, non-invasive means, integrating observation of bodily responses with empirical trial. During the medieval period and into the 19th century, rectal administration via enemas emerged as a significant route, building on ancient precedents but gaining institutional prominence in Europe. Enemas, or clysters, were routinely used from the Middle Ages onward to purge the body of supposed toxins, with physicians employing animal bladders or syringes to deliver herbal infusions, often for treating constipation or fevers. A pivotal advancement in parenteral routes occurred in 1656 when English scientist Christopher Wren conducted the first recorded intravenous injections in dogs, using a quill and animal bladder to administer substances like wine and opium, demonstrating the potential for direct bloodstream delivery despite rudimentary tools.^[13] In 1853, the invention of the hypodermic needle by French surgeon Charles Pravaz—a piston syringe with a hollow silver needle—enabled subcutaneous and intramuscular injections, revolutionizing precise drug delivery for conditions like pain management.^[14] The 20th century marked rapid innovations in specialized routes, driven by pharmaceutical advancements and medical needs. In the 1920s, the discovery of insulin by Frederick Banting and colleagues led to its first subcutaneous administration in humans on January 23, 1922, to 14-year-old Leonard Thompson, transforming diabetes treatment from fatal to manageable through regular injections.^[15] Inhalation therapy advanced significantly in 1956 with the introduction of the first pressurized metered-dose inhaler (MDI) by Riker Laboratories, delivering epinephrine or isoproterenol aerosols for asthma relief and establishing pulmonary delivery as a targeted, patient-friendly option.^[16] The late 20th century saw the rise of transdermal systems, exemplified by the 1979 FDA approval of the scopolamine patch for motion sickness prevention, which used a membrane-controlled reservoir to provide sustained release through the skin, paving the way for broader applications like nicotine replacement.^[17] These milestones shifted drug administration toward more controlled, site-specific methods, influencing modern classifications of enteral, parenteral, and topical routes.

Classification

Enteral Routes

Enteral routes of administration involve the delivery of medications into the gastrointestinal (GI) tract, where drugs are absorbed through the GI mucosa into the systemic circulation.^[18] This approach encompasses methods that utilize the digestive system for drug uptake, distinguishing it from routes that bypass the GI tract.^[2] The primary enteral methods include oral administration, where drugs are swallowed in forms such as tablets or capsules; rectal administration via suppositories or enemas; and nasogastric administration through a feeding tube inserted into the stomach.^[18]^[19] Oral delivery is the most common due to its simplicity, while rectal and nasogastric routes are employed when swallowing is impaired or for targeted delivery.^[5] Absorption via enteral routes primarily occurs in the small intestine, influenced by factors such as GI pH variations, enzymatic degradation, and motility.^[20] Drugs absorbed from the GI tract enter the portal vein and undergo first-pass metabolism in the liver, where enzymes metabolize a portion of the drug, reducing its bioavailability to the systemic circulation.^[9] Oral drug bioavailability can range from 0% to nearly 100%, depending on the compound's susceptibility to these processes.^[7] Enteral routes offer advantages such as being non-invasive and patient-friendly, facilitating self-administration in many cases.^[5] However, they are subject to disadvantages including variable absorption rates affected by food intake, GI motility, and pH changes, which can delay onset and reduce predictability.^[20] For example, oral ibuprofen, a nonsteroidal anti-inflammatory drug, is widely used for analgesia but may exhibit inconsistent absorption when taken with meals.^[21] In contrast, rectal administration partially avoids the first-pass effect due to drainage via both portal and systemic veins, improving bioavailability for certain drugs and making it suitable for pediatrics or unconscious patients; rectal antiemetics like promethazine are employed in such scenarios to manage nausea when oral intake is not feasible.^[22]

Parenteral Routes

Parenteral routes of administration involve the delivery of medications directly into the body through injections or infusions, bypassing the gastrointestinal tract to achieve systemic effects. These methods utilize needles, syringes, or catheters to introduce drugs into tissues, blood vessels, or body cavities outside the digestive system, ensuring more predictable absorption compared to oral routes. The primary parenteral methods include intravenous (IV), intramuscular (IM), subcutaneous (SC), and intradermal administration. Intravenous delivery can occur as a bolus injection for immediate effect or as a continuous infusion for sustained release, directly accessing the bloodstream. Intramuscular injections target muscle tissue, such as the deltoid or gluteal muscles, while subcutaneous injections deposit drugs into the fatty layer beneath the skin, and intradermal injections place small volumes into the dermis layer. Absorption characteristics vary by method and site. Intravenous administration provides 100% bioavailability since the drug enters the circulation directly, without first-pass metabolism. In contrast, intramuscular and subcutaneous routes achieve bioavailability dependent on local blood flow and tissue properties; for instance, the deltoid muscle offers faster absorption due to higher vascularity compared to the gluteal muscle. These routes offer advantages such as rapid onset of action, ideal for emergencies or conditions requiring precise dosing, but they are invasive, carrying risks of infection, pain, and tissue damage at the injection site. Examples include intramuscular vaccines for immune response stimulation and intravenous chemotherapy for targeted cancer treatment. Specific applications highlight their utility: intradermal injections are used for allergy testing due to the skin's immune-rich environment, eliciting localized reactions for diagnosis, while subcutaneous insulin administration provides slower, sustained release for diabetes management.

Topical and Mucosal Routes

Topical and mucosal routes involve the application of drugs directly to external surfaces such as the skin or non-gastrointestinal mucous membranes, including those of the eyes, ears, nose, oral cavity, lungs, and vagina, to achieve primarily local effects or limited systemic absorption without involving the digestive tract.^[23] These methods are non-invasive and target specific sites for therapeutic action, such as treating skin conditions, ocular disorders, or providing rapid relief from angina via oral mucosa.^[24] Primary methods encompass transdermal patches for sustained skin delivery, ocular drops for eye conditions, otic solutions for ear infections, intranasal sprays for nasal congestion or vaccination, inhalation via aerosols or nebulizers for respiratory conditions like asthma, vaginal creams or suppositories for gynecological infections, and oral mucosal applications like sublingual tablets or buccal films. For instance, transdermal patches deliver drugs such as nicotine or fentanyl across the skin for systemic effects over hours or days, while ocular drops treat glaucoma by applying prostaglandins or beta-blockers directly to the cornea.^[8] Intranasal sprays, such as those for flu vaccines like FluMist, leverage the nasal mucosa for immune response induction, and sublingual nitroglycerin tablets provide quick vasodilation for chest pain.^[25] Buccal formulations, placed against the cheek, avoid swallowing and direct absorption into the bloodstream.^[24] Inhalation delivers bronchodilators like albuterol to the lungs for rapid local action in respiratory distress, and vaginal metronidazole treats bacterial vaginosis with minimal systemic exposure.^[7]^[5] Absorption via these routes varies significantly due to anatomical barriers; the skin's stratum corneum acts as a primary lipid barrier, limiting systemic uptake to low levels for most hydrophilic or large-molecule drugs, often requiring enhancers for penetration.^[26] In contrast, mucosal routes enable faster absorption owing to their rich vascularity and thinner epithelium, as seen with sublingual nitroglycerin, where the drug bypasses hepatic first-pass metabolism for onset within minutes via sublingual veins.^[27] Ocular absorption through the cornea is inefficient, with only about 1-5% of applied drops reaching the anterior chamber for glaucoma therapy, leading to substantial nasolacrimal drainage and potential systemic exposure.^[28] These routes offer advantages like targeted localized action, which minimizes systemic side effects and gastrointestinal irritation, and ease of self-administration for improved patient compliance, as with hydrocortisone creams for eczema that provide anti-inflammatory effects with minimal percutaneous absorption (typically 1-7% systemically on intact skin).^[23]^[29] However, disadvantages include poor penetration for polar or high-molecular-weight compounds across the skin, potential local irritation or allergic reactions like contact dermatitis, and limited drug loading capacity, restricting use to potent agents requiring low doses.^[23] Intranasal vaccines exemplify mucosal benefits by eliciting strong local immunity but face challenges from mucociliary clearance reducing antigen residence time.^[30]

Factors Influencing Selection

Convenience and Patient Compliance

The convenience of a route of administration significantly influences patient compliance, with non-invasive options like oral delivery often preferred over invasive methods such as intravenous infusion due to ease of use and reduced discomfort.^[31] In patient surveys, up to 79% favor oral tablets over injections or infusions when efficacy and safety are comparable, primarily for their simplicity in daily routines.^[31] Self-administration feasibility further enhances adherence, as routes enabling independent use—such as oral or subcutaneous—minimize reliance on healthcare providers and fit better into patients' lifestyles.^[32] Less frequent dosing schedules also play a key role, with evidence showing higher compliance rates for once-daily regimens compared to multiple daily administrations.^[33] Patient-specific factors tailor route selection to improve compliance across diverse populations. In infants and young children, where oral administration may be difficult due to swallowing challenges or vomiting, the rectal route offers a practical alternative for delivering medications like laxatives for constipation management.^[34] For adults with conditions requiring regular injections, such as diabetes, prefilled subcutaneous pens facilitate self-administration and boost adherence by simplifying the process and reducing injection-related anxiety compared to traditional vials and syringes.^[35] Patients with lifestyles prone to forgetfulness, including those with cognitive impairments like dementia, benefit from transdermal patches, which provide steady delivery over days or weeks without daily prompting, leading to improved treatment persistence.^[36] Overall adherence rates underscore the impact of route complexity, with studies reporting around 50% non-adherence among patients on intricate regimens, such as multiple daily injections for chronic diseases.^[37] Oral routes exemplify high convenience for long-term conditions like hypertension, where simple pill-taking supports sustained compliance and better blood pressure control.^[38] In asthma management, advanced inhalation devices, including those with reminders, have demonstrated enhanced patient adherence by making dosing more intuitive and less error-prone than traditional methods.^[39] These practical aspects must be balanced against therapeutic requirements to optimize outcomes.

Therapeutic and Pharmacokinetic Considerations

The selection of a route of administration is fundamentally guided by therapeutic objectives, which determine whether the drug's action should be localized or systemic. Local administration targets specific sites to minimize systemic exposure and side effects, such as applying topical corticosteroids directly to skin rashes for anti-inflammatory effects confined to the affected area.^[40] In contrast, systemic routes like intravenous (IV) infusion are preferred for emergencies requiring immediate widespread distribution, such as epinephrine in anaphylaxis, where rapid circulation ensures quick onset across the body.^[2] Pharmacokinetic properties, including bioavailability and onset of action, further influence route choice to optimize drug efficacy and timing. Bioavailability (F) quantifies the fraction of an administered dose that reaches systemic circulation unchanged, calculated as:

F = \frac{\text{AUC}_{\text{test}}}{\text{AUC}_{\text{reference}}} \times 100\%

where AUC represents the area under the plasma concentration-time curve, typically comparing oral to IV administration as the reference (F = 1 for IV).^[41] Oral routes often exhibit lower bioavailability due to gastrointestinal absorption variability and hepatic first-pass metabolism, while IV achieves complete bioavailability. Onset of action varies significantly: IV delivery occurs in seconds by directly entering the bloodstream, whereas oral administration typically takes 30-60 minutes due to absorption and transit through the digestive system.^[42]^[8] Routes also affect drug distribution, particularly for barriers like the blood-brain barrier (BBB), which restricts central nervous system (CNS) access for many therapeutics. Intranasal administration enables direct nose-to-brain transport via olfactory and trigeminal pathways, bypassing the BBB to enhance CNS delivery of drugs like peptides for neurological conditions.^[43] This route leverages the nasal cavity's proximity to the brain, allowing faster and more targeted distribution compared to systemic options that require higher doses to overcome BBB limitations.^[44] Specific examples illustrate these considerations in clinical practice. Inhalation routes provide rapid local delivery to the lungs for chronic obstructive pulmonary disease (COPD), where bronchodilators like albuterol achieve onset within minutes by directly targeting airway smooth muscle, reducing systemic exposure.^[45] Rectal administration is advantageous in liver disease to bypass partial hepatic first-pass metabolism; approximately 50% of rectally absorbed drugs enter systemic circulation via inferior and middle rectal veins, avoiding full liver processing and improving bioavailability for analgesics or antiemetics in patients with impaired hepatic function.^[22]

Safety and Formulation Factors

Safety risks associated with routes of administration vary by method and can include infection, local irritation, and systemic adverse effects. Parenteral routes, such as intravenous (IV) and intramuscular (IM) injections, carry a heightened risk of infection due to breaching the skin barrier, with complications like abscesses or sepsis possible if aseptic techniques are not followed.^[2] IV administration specifically risks rapid drug delivery leading to overdose or severe cardiopulmonary effects, such as hypotension or arrhythmias, particularly with vasoactive agents.^[2] Topical and mucosal routes may cause local irritation, including skin rashes from transdermal patches or corneal abrasions from eye drops, exacerbating discomfort in sensitive patients.^[3] Formulation requirements differ significantly across routes to ensure compatibility and efficacy. Parenteral formulations must be sterile and nonpyrogenic to prevent microbial contamination and endotoxemia, often achieved through aseptic processing and filtration as mandated by regulatory standards.^[46] Oral formulations require solubility enhancers, such as cyclodextrins or solid dispersions, for poorly water-soluble drugs to improve gastrointestinal absorption and bioavailability without compromising stability.^[47] Transdermal systems necessitate pressure-sensitive adhesives, like acrylic or silicone-based polymers, to maintain skin contact while controlling drug release and minimizing residue upon removal.^[48] Contraindications for specific routes help mitigate these risks. The oral route is contraindicated in patients with severe nausea or vomiting, as it impairs absorption and increases aspiration risk, necessitating alternatives like IV or rectal administration.^[49] IM injections are contraindicated in individuals with bleeding disorders or on anticoagulants, due to the potential for hematoma formation from vascular damage.^[50] Representative examples illustrate these factors in practice. Liposomal formulations for IV chemotherapy agents, such as doxorubicin, encapsulate the drug to reduce cardiotoxicity by altering distribution and clearance, allowing higher doses with lower systemic exposure.^[51] Buffered eye drops, pH-adjusted to approximately 7.4 to match tear fluid, prevent stinging and irritation upon instillation, enhancing patient tolerance for repeated use.^[52]

Emerging Developments

Novel Delivery Methods

Microneedle patches represent a painless transdermal alternative to hypodermic injections, utilizing arrays of microscopic needles to deliver drugs or vaccines directly into the skin's outer layers without reaching deeper nerves or blood vessels. These patches enhance patient compliance by eliminating needle phobia and sharps waste, while enabling controlled release through dissolving, coated, or hollow designs. The BD Soluvia™ system, approved by the FDA in 2012, was the first microneedle device cleared for intradermal vaccine delivery, such as influenza vaccines, demonstrating improved immune responses in clinical studies. In the 2020s, advancements have focused on vaccine applications, including experimental dissolving microneedle patches for COVID-19 and influenza, which showed comparable immunogenicity to intramuscular injections in preclinical models with reduced dosing volumes.^[53]^[54]^[55] Implantable devices offer long-acting subcutaneous delivery, providing steady drug release over months to years, which minimizes frequent dosing and improves adherence for chronic conditions. Probuphine, a buprenorphine subdermal implant consisting of four ethylene-vinyl acetate (EVA) copolymer rods, received FDA approval in 2016 for maintenance treatment of opioid use disorder in stable patients, delivering therapeutic levels for up to six months via insertion in the upper arm. Clinical trials demonstrated that Probuphine achieved steady-state plasma buprenorphine concentrations of approximately 1 ng/mL (range: 0.3–2.4 ng/mL), comparable to daily sublingual dosing, with reduced risks of misuse due to its tamper-resistant design. These implants expand parenteral routes by enabling site-specific, zero-order kinetics release, as seen in similar systems for contraceptives and antipsychotics.^[56]^[57] Targeted nanoparticles facilitate site-specific parenteral delivery by engineering particles with ligands or surface modifications to homing in on diseased tissues, while also enhancing mucosal uptake through mucoadhesive or mucopenetrating properties that overcome barriers like mucus clearance. Polymeric nanoparticles, such as those coated with polyethylene glycol (PEG), improve bioavailability by prolonging circulation and enabling endocytosis at mucosal sites, with studies showing up to 10-fold increased uptake in intestinal or nasal models compared to free drugs. For instance, chitosan-based nanoparticles have been developed for nasal mucosal delivery of insulin, achieving 20-30% relative bioavailability in animal models by promoting paracellular transport and mucoadhesion. These systems reduce off-target effects and dosing frequency, with ongoing clinical translations for vaccines and oncology applications.^[58]^[59] Buccal films provide rapid absorption via the oral mucosa, bypassing first-pass metabolism for faster onset, particularly suited for analgesics and antiemetics. FDA-approved examples include Onsolis (fentanyl buccal soluble film), cleared in 2009 for breakthrough cancer pain, which dissolves in 15-30 minutes to deliver 200-1600 mcg doses with peak plasma levels in 30-60 minutes, offering analgesia within 15 minutes in clinical use. Similarly, Belbuca (buprenorphine buccal film), approved in 2015, treats opioid dependence with strengths from 75-900 mcg, achieving 30-50% higher bioavailability than sublingual tablets due to enhanced mucosal retention. These films use polymers like hydroxypropyl cellulose for unidirectional release toward the mucosa, improving patient convenience over liquids or tablets.^[60]^[61] Iontophoresis enhances topical penetration by applying a mild electric current (typically 0.5-2 mA) to drive charged drug ions across the stratum corneum, increasing flux rates by 10-100 times for molecules like peptides without skin disruption. FDA-cleared devices, such as the Iontophor Patch system, deliver lidocaine for local anesthesia, achieving dermal concentrations sufficient for pain relief in 10-20 minutes during clinical procedures. Although some products like the Zecuity sumatriptan iontophoretic patch were recalled in 2016 due to safety concerns, approved systems for fentanyl and anti-inflammatory drugs continue to support enhanced transdermal delivery in dermatology and pain management. This method expands topical routes for hydrophilic compounds otherwise limited by passive diffusion.^[62]^[63]

Research and Future Trends

Ongoing research in gene therapy highlights the intravenous (IV) and intrathecal routes for delivering viral vectors, particularly adeno-associated virus (AAV) vectors, to target central nervous system disorders. For instance, onasemnogene abeparvovec (Zolgensma), approved in 2019 for spinal muscular atrophy (SMA) via IV administration in infants under two years, is now under investigation for intrathecal delivery in older pediatric patients to achieve broader transduction with lower doses and reduced immunogenicity risks. The phase III STEER trial met its primary endpoint in December 2024, demonstrating statistically significant improvements in motor function for treatment-naïve patients aged 2-18 years.^[64]^[65] Intrathecal administration enhances central nervous system penetration compared to systemic IV routes, as demonstrated in preclinical models where it minimizes off-target liver transduction.^[66] Advancements in 3D-printed oral dosage forms are enabling personalized drug release profiles tailored to individual patient needs, such as varying release kinetics for chronic conditions. These forms allow for precise control over dosage, shape, and multilayer structures to achieve sustained or pulsatile release, improving adherence in pediatric and geriatric populations.^[67]01766-3) Recent studies have shown that 3D printing facilitates multidrug combinations in single polypills, optimizing therapeutic outcomes while reducing polypharmacy burdens.^[68] A key challenge in route optimization is enhancing bioavailability for orally administered peptides, which face enzymatic degradation and poor permeability in the gastrointestinal tract. Nanotechnology addresses this through carriers like chitosan-based nanoparticles, which protect peptides and promote absorption via mucoadhesion and paracellular transport, with preclinical data indicating up to 10-fold bioavailability improvements.^[69] As of 2025, clinical trials are evaluating lipid nanoparticles and polymer-peptide conjugates for oral semaglutide analogs, reporting enhanced systemic exposure in phase II studies without significant adverse effects.^[70]^[71] Future trends point toward wireless-controlled implants for on-demand drug release, integrating microelectromechanical systems to enable remote activation via external signals like ultrasound or magnetic fields. These devices offer precise dosing adjustments, potentially reducing the need for frequent administrations in chronic diseases such as diabetes or cancer.^[72] Prototypes have demonstrated controlled release of multiple drugs from biodegradable reservoirs, with biocompatibility confirmed in animal models.^[73] Artificial intelligence (AI) is emerging as a tool for optimizing route selection by analyzing patient-specific data, including pharmacokinetics, genetics, and real-time biomarkers, to predict the most effective administration method. Machine learning models can recommend routes like transdermal over oral for poor absorbers, improving efficacy while minimizing toxicity, as shown in simulations integrating electronic health records.^[74]^[75] Research on ocular and intravitreal routes is expanding to develop long-acting implants that sustain drug levels in the posterior segment, addressing challenges like frequent injections for conditions such as age-related macular degeneration. Biodegradable inserts and nanoparticle-laden hydrogels are in phase III trials, providing release over 6-12 months and reducing injection frequency by up to 80%.^[76]^[77] These innovations prioritize minimally invasive periocular alternatives to traditional intravitreal injections.^[78] In veterinary medicine, underexplored applications of advanced routes include nanogel-based mucosal delivery for vaccines and therapeutics, enhancing immune responses in livestock and companion animals via intranasal or oral administration. Long-acting injectables, such as subcutaneous implants, are gaining traction for sustained antimicrobial release, with studies showing improved compliance and reduced resistance risks in poultry and cattle.^[79]^[80] Precision pharmacology trends, including targeted nanoparticles, are addressing species-specific barriers to bioavailability.^[81]

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