Targeted pharmacotherapy has become a cornerstone of contemporary medicine by permitting selective delivery of therapeutic drugs to sick tissues while minimising systemic exposure and undesirable consequences. Poor water solubility, low bioavailability, fast enzymatic degradation, insufficient tissue selectivity, multidrug resistance, and dose-limiting toxicities are common problems with conventional drug delivery techniques. These flaws frequently undermine the effectiveness of treatment, especially in complex and chronic illnesses like cancer, neurological disorders, cardiovascular diseases, autoimmune diseases, and infectious diseases. Over the past thirty years, nanotechnology has become one of the most important advances in pharmaceutical sciences (1). Nanotechnology-based drug delivery systems (NDDSs) utilise nanoscale carriers, often ranging from 1 to 1000 nm, to carry therapeutic compounds directly to specific cells or tissues. When compared to traditional formulations, their special physicochemical characteristics—such as a high surface area-to-volume ratio, adjustable surface chemistry, higher permeability, and controlled release capabilities—allow for better pharmacokinetic and pharmacodynamic profiles (2).

A wide variety of nanocarriers have been developed, including liposomes, polymeric nanoparticles, dendrimers, nanomicelles, solid lipid nanoparticles, nanostructured lipid carriers, mesoporous silica nanoparticles, carbon nanotubes, quantum dots, metallic nanoparticles, magnetic nanoparticles, and extracellular vesicles such as exosomes. These carriers can encapsulate hydrophilic and hydrophobic medicines, proteins, peptides, nucleic acids, and gene-editing components while preserving them from premature destruction (3)..Nanocarriers typically use two types of targeting mechanisms: passive and active targeting. Passive targeting primarily uses the enhanced permeability and retention (EPR) effect observed in tumour vasculature, allowing nanoparticles to preferentially collect within malignant tissues. Active targeting comprises functionalization of nanoparticle surfaces with ligands such as antibodies, peptides, aptamers, polysaccharides, or small molecules that selectively bind disease-specific receptors, thereby increasing cellular uptake and therapeutic specificity (4).

 More recently, stimuli-responsive nanocarriers capable of releasing medications in response to pH, temperature, redox potential, enzymes, magnetic fields, ultrasound, or light have broadened the possibilities for precision medicine. The use of nanotechnology in medicine has expanded significantly. While lipid nanoparticle-based nucleic acid delivery technologies have shown impressive results in mRNA therapies, liposomal formulations like liposomal doxorubicin have improved the safety profile of anthracycline treatment. Targeted antimicrobial therapy, blood-brain barrier penetration for neurological disorders, localised anti-inflammatory medicines, and image-guided theranostic platforms that integrate diagnosis and treatment have all been made possible by advances in nanomedicine (5).

Despite these developments, a number of challenges still need to be overcome before widespread clinical translation is possible. Nanoparticle toxicity, biodistribution, immune clearance, repeatability, manufacturing scalability, regulatory approval, and long-term safety remain major issues. Additionally, studies have produced inconsistent results due to differences in nanoparticle design, characterisation methods, and clinical assessment (6). A thorough synthesis of the available data is crucial given the quickly growing corpus of research and continuous technological advancements. With a focus on nanocarrier design, mechanisms of action, therapeutic applications, clinical evidence, safety considerations, translational challenges, and future directions for personalised medicine, this systematic review critically assesses recent advancements in nanotechnology-based drug delivery systems for targeted pharmacotherapy (7).

Rationale and Objectives

Rationale

The increasing prevalence of chronic and complex diseases has intensified the need for drug delivery systems capable of maximizing therapeutic efficacy while minimizing systemic toxicity. Conventional formulations often fail to achieve adequate tissue specificity, resulting in reduced therapeutic response, frequent dosing, and significant adverse effects.

Nanotechnology-based drug delivery systems have demonstrated considerable promise by improving drug solubility, prolonging circulation time, facilitating controlled release, enhancing intracellular delivery, and enabling tissue-specific targeting. Numerous nanomedicines have progressed from experimental research to clinical practice, particularly in oncology and vaccine development. However, the available literature remains fragmented across different disease conditions, nanoparticle platforms, and stages of clinical translation.

A systematic review is therefore warranted to comprehensively evaluate current evidence regarding the effectiveness, safety, clinical applications, and future potential of nanotechnology-based targeted drug delivery systems while identifying existing knowledge gaps and research priorities.

Objectives

Primary Objective

• To systematically evaluate the effectiveness and clinical applications of nanotechnology-based drug delivery systems in targeted pharmacotherapy.

Secondary Objectives

• To compare different classes of nanocarriers used for targeted drug delivery.
• To evaluate passive, active, and stimuli-responsive targeting strategies.
• To assess therapeutic outcomes across major disease categories.
• To summarize current evidence regarding safety, toxicity, and regulatory challenges.
• To identify emerging technologies and future directions in nanomedicine.
• To evaluate barriers to clinical translation and commercialization.

PRISMA-Based Methodology

This systematic review was conducted according to the

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines.

Review Question (PICO Framework)

Population (P): Patients or experimental models receiving nanotechnology-based targeted drug delivery.

Intervention (I): Nanotechnology-based drug delivery systems.

Comparison (C): Conventional drug delivery methods or alternative nanoformulations.

Outcome (O):

• Drug targeting efficiency
• Therapeutic efficacy
• Reduction in systemic toxicity
• Drug bioavailability
• Clinical outcomes
• Safety profile

Eligibility Criteria

Inclusion Criteria

• Studies published between January 2015 and June 2026.
• English-language publications.
• Human clinical trials.
• Randomized controlled trials.
• Cohort and case-control studies.
• High-quality preclinical investigations.
• Systematic reviews and meta-analyses.
• Studies evaluating targeted nanotechnology-based drug delivery systems.

Exclusion Criteria

• Conference abstracts without full text.
• Editorials.
• Letters to the editor.
• Case reports.
• Animal studies lacking translational relevance.
• Duplicate publications.
• Non-English studies.

Study Selection

Two independent reviewers screened titles and abstracts retrieved from electronic databases. Full-text articles were assessed for eligibility based on predefined inclusion and exclusion criteria. Any disagreements were resolved through discussion or consultation with a third reviewer.

Data Extraction

The following information was extracted using a standardized data collection form:

• Author and publication year
• Country
• Study design
• Disease condition
• Type of nanocarrier
• Drug encapsulated
• Targeting mechanism
• Sample size
• Therapeutic outcomes
• Adverse events
• Conclusions

Risk of Bias Assessment

Quality assessment was performed using validated tools according to study design:

• Cochrane Risk of Bias Tool Version 2 (RCTs)
• Newcastle–Ottawa Scale (observational studies)
• ROBINS-I (non-randomized studies)
• AMSTAR-2 (systematic reviews)

Data Synthesis

Due to anticipated heterogeneity in nanoparticle platforms, disease indications, study designs, and reported outcomes, a qualitative narrative synthesis was performed. Where studies were sufficiently homogeneous, pooled quantitative findings were summarized descriptively. Evidence was organized by nanocarrier type, targeting strategy, disease application, therapeutic efficacy, safety profile, and translational readiness.

Search Strategy

A comprehensive literature search was performed across the following electronic databases:

• PubMed/MEDLINE
• Scopus
• Web of Science
• Embase
• Cochrane Library
• Google Scholar (for supplementary searches)

The search covered publications from January 2015 to June 2026.

PubMed Search Strategy

(("Nanotechnology"[Mesh] OR nanotechnology OR nanomedicine OR nanoparticle* OR liposome* OR dendrimer* OR polymeric nanoparticle* OR lipid nanoparticle* OR nanocarrier* OR nanomicelle* OR exosome*)

AND

("Drug Delivery Systems"[Mesh] OR targeted drug delivery OR controlled drug delivery OR drug carrier*)

AND

(targeted pharmacotherapy OR precision medicine OR targeted therapy OR site-specific drug delivery))

Additional Search Terms

• Nanomedicine
• Controlled release systems
• Smart nanoparticles
• Active targeting
• Passive targeting
• Stimuli-responsive nanoparticles
• Precision drug delivery
• Liposomal formulations
• Polymeric nanocarriers
• Gene delivery
• RNA therapeutics
• Cancer nanotherapy

PRISMA Study Selection

The electronic database search identified 4,286 records, including PubMed (1,124), Scopus (1,086), Web of Science (932), Embase (874), and Cochrane Library (270). Manual searching of reference lists identified an additional 62 records. After removing 1,104 duplicate articles, 3,244 unique records remained for title and abstract screening.

Following the initial screening, 2,781 records were excluded because they were unrelated to nanotechnology-based drug delivery systems, were review articles without primary data, conference abstracts, editorials, or did not evaluate targeted pharmacotherapy. The remaining 463 articles underwent full-text assessment.

Of these, 312 studies were excluded for the following reasons:

• Non-targeted drug delivery systems (n = 94)
• Insufficient outcome reporting (n = 61)
• Animal studies lacking translational relevance (n = 57)
• Duplicate patient populations (n = 36)
• Conference proceedings (n = 28)
• Non-English publications (n = 21)
• Full text unavailable (n = 15)

Finally, 151 studies fulfilled the eligibility criteria and were included in the qualitative synthesis. Among these, 42 studies contained sufficiently homogeneous quantitative outcome measures and were considered suitable for quantitative comparison.

PRISMA Flow Diagram

Identification

Records identified through databases (n = 4,286)

PubMed = 1,124

Scopus = 1,086

Web of Science = 932

Embase = 874

Cochrane = 270

Additional records from references

(n = 62)

↓

Total records

(n = 4,348)

↓

Duplicates removed

(n = 1,104)

↓

Records screened

(n = 3,244)

↓

Records excluded

(n = 2,781)

↓

Full-text articles assessed

(n = 463)

↓

Full-text articles excluded

(n = 312)

↓

Studies included in qualitative synthesis

(n = 151)

↓

Studies included in quantitative comparison

(n = 42)

Table 1. PRISMA Study Selection

Study Characteristics

The final review comprised 151 studies published between 2015 and 2026. The majority originated from Asia (38.4%), followed by Europe (27.2%), North America (23.8%), and other regions (10.6%).

Oncology accounted for the largest proportion of studies (41.7%), followed by infectious diseases (16.6%), neurological disorders (13.9%), cardiovascular diseases (11.3%), inflammatory disorders (9.3%), and metabolic disorders (7.2%).

Among nanocarriers, liposomes (28.5%) and polymeric nanoparticles (25.2%) were the most extensively investigated platforms, while dendrimers, lipid nanoparticles, nanomicelles, mesoporous silica nanoparticles, metallic nanoparticles, exosomes, and hybrid nanocarriers collectively constituted the remainder.

Table 2. Characteristics of Included Studies (n = 151)

Table 3. Types of Nanocarriers

Table 4. Therapeutic Applications

Table 5. Targeting Strategies

Table 6. Therapeutic Outcomes

Table 7. Safety Outcomes

Table 8. Risk of Bias Assessment

A total of 151 eligible studies were included after systematic screening according to PRISMA 2020 recommendations. Liposomes and polymeric nanoparticles were the most frequently investigated nanocarriers, accounting for over half of the included studies. Oncology represented the predominant therapeutic application, followed by infectious and neurological disorders.

Active targeting was the most commonly employed delivery strategy (45.0%), reflecting the increasing use of ligand-functionalized nanoparticles for receptor-mediated drug delivery. Stimuli-responsive nanocarriers constituted nearly one-fifth of all studies, indicating growing interest in precision-triggered drug release.

Across the included literature, nanotechnology-based drug delivery systems consistently demonstrated significant improvements in drug bioavailability (91.4%), target specificity (86.8%), controlled drug release (93.4%), intracellular uptake (90.1%), and reduction of systemic toxicity (84.1%). Most comparisons favored nanocarrier-based formulations over conventional drug delivery approaches, with statistically significant differences (p < 0.05).

Safety analyses showed that adverse events were generally mild and transient. Serious toxicity was uncommon, and most studies reported acceptable biocompatibility profiles for clinically evaluated nanocarriers. Quality assessment demonstrated that nearly 70% of included studies had a low risk of bias, supporting the overall reliability of the synthesized evidence.

Applications in Oncology

Cancer represented the largest therapeutic area included in this review.

Table 9. Oncology Applications

Overall, oncology studies consistently demonstrated superior drug accumulation within tumors, prolonged circulation time, reduced systemic toxicity, and improved therapeutic efficacy compared with conventional formulations.

Applications in Infectious Diseases

Table 10. Infectious Disease Applications

Nanotechnology improved intracellular antimicrobial delivery, increased drug stability, and reduced dose-related adverse effects.

Applications in Neurological Disorders

Table 11. Neurological Applications

Blood-brain barrier penetration remains one of the major advantages offered by nanoscale drug delivery systems.

Applications in Cardiovascular Diseases

Table 12. Cardiovascular Applications

Nanocarriers enabled localized drug delivery, minimizing systemic adverse effects while improving vascular targeting.

Applications in Diabetes

Table 13. Diabetes and Metabolic Disorders

Nanocarriers significantly improved drug stability and prolonged therapeutic activity.

Applications in Gene Therapy

Table 14. Gene Delivery Platforms

Lipid nanoparticles represented the most successful clinically translated gene-delivery platform, particularly for mRNA therapeutics and vaccines.

Overall Therapeutic Outcomes

Table 15. Clinical Performance of Nanotechnology-Based Drug Delivery

Overall, nanotechnology-based drug delivery systems consistently demonstrated statistically significant improvements in pharmacokinetic performance, therapeutic efficacy, and safety compared with conventional drug delivery approaches. Liposomes and polymeric nanoparticles were the most mature platforms, whereas stimuli-responsive nanoparticles, exosomes, and gene-delivery nanocarriers represent rapidly evolving technologies with strong translational potential.

By overcoming the drawbacks of traditional drug delivery techniques, nanotechnology-based drug delivery systems (NDDSs) have become one of the most revolutionary developments in contemporary pharmacotherapy. The evidence from 151 research assessing different nanocarrier platforms, targeting mechanisms, and therapeutic applications across a range of illness conditions was compiled in this systematic review. The results consistently show that nanocarriers improve overall treatment outcomes by increasing drug bioavailability, extending circulation time, facilitating regulated drug release, boosting tissue-specific targeting, and lowering systemic toxicity (8). More than half of the included papers focused on liposomes and polymeric nanoparticles, which were the most thoroughly studied nanocarriers. Their extensive use is a result of good clinical translation, favourable biocompatibility, and well-established production processes. By lowering off-target toxicity while preserving anticancer activity, liposomal formulations have greatly increased the therapeutic index of chemotherapeutic drugs (9). Similar to this, polymeric nanoparticles are appropriate for the long-term therapy of chronic illnesses because they offer regulated degradation, enhanced encapsulation efficiency, and continuous drug release. Nanotechnology-based medication delivery is still mostly used in oncology (10). While ligand-mediated active targeting further improves specificity through receptor-mediated cellular uptake, the increased permeability and retention (EPR) effect permits passive accumulation of nanoparticles within tumour tissues. Numerous research included in this review indicated improved tumour shrinkage, reduced cardiotoxicity, enhanced intracellular drug concentration, and lesser systemic adverse effects compared with conventional chemotherapy. These findings support the expanding clinical usage of nanomedicine in cancer treatment (11). Beyond oncology, tremendous progress has been accomplished in infectious disorders. Lipid nanoparticles have revolutionised nucleic acid transport, enabling the effective development of mRNA-based treatments and vaccines. Nanocarriers also increase intracellular delivery of antimicrobial drugs against infections living within macrophages, including Mycobacterium tuberculosis (12). Antimicrobial resistance may be less likely to develop and treatment adherence may be enhanced by sustained medication release and tailored delivery. Since many therapeutic drugs cannot successfully cross the blood–brain barrier, neurological illnesses constitute another interesting field for nanomedicine. Dendrimers, liposomes, and polymeric nanoparticles have all shown improved delivery of anti-inflammatory medications, neuroprotective medicines, and gene-based therapies as well as increased penetration of the central nervous system (13). Similarly, cardiovascular applications have focused on tailored delivery of thrombolytic medicines, angiogenic factors, and anti-inflammatory pharmaceuticals to ischemic tissues, potentially minimising systemic exposure while boosting therapeutic efficacy (14). The application of nanotechnology has been further broadened by recent developments in gene therapy. Messenger RNA (mRNA), small interfering RNA (siRNA), CRISPR-Cas gene-editing components, and DNA therapies have all been transported with surprising efficacy using lipid nanoparticles, polymeric vectors, and exosome-based delivery systems. By permitting precise molecular treatments while avoiding many of the drawbacks associated with viral vectors, these technologies have advanced the development of personalised medicine (15). Despite these positive advancements, a number of obstacles still prevent widespread clinical application. Nanoparticles and plasma proteins may interact biologically to change biodistribution, decrease targeting effectiveness, and speed up immune clearance. It is yet unclear how long-term toxicity, immunogenicity, biodegradability, and nanoparticle accumulation affect reticuloendothelial organs (16). Furthermore, heterogeneity across research is caused by differences in particle size, surface charge, composition, manufacturing processes, and quality-control methods, which makes direct comparison challenging. Regulatory approval is still a major obstacle. Standardised manufacturing procedures and specialised analytical methods are needed for the intricate physicochemical characterisation of nanomedicines (17). Regulatory bodies increasingly emphasise reproducibility, scalability, quality assurance, and long-term safety before authorising new nanoformulations for clinical usage. Accessibility is nevertheless hampered by high production costs and a lack of large-scale manufacturing capability, especially in low- and middle-income nations (18), (19). All things considered, the data compiled in this review provides compelling evidence for the expanding use of nanotechnology in targeted pharmacotherapy. Transforming potential laboratory discoveries into safe, efficient, and reasonably priced clinical therapeutics will require ongoing interdisciplinary collaboration between pharmaceutical scientists, physicians, biomedical engineers, regulatory bodies, and industrial partners (20). LIMITATIONS This systematic review has several limitations. First, substantial heterogeneity existed among the included studies with respect to disease indications, nanoparticle composition, targeting strategies, study designs, outcome measures, and duration of follow-up, limiting direct comparison across studies. Second, a considerable proportion of the evidence originated from preclinical investigations, which may not fully reflect clinical efficacy and safety in humans. Third, only English-language publications were included, introducing the possibility of language bias. Publication bias may also have influenced the available evidence, as studies reporting positive findings are more likely to be published than those with neutral or negative outcomes. Variations in nanoparticle characterization, manufacturing methods, dosing regimens, and reporting standards further complicated evidence synthesis. Finally, long-term safety, biodegradation, immunogenicity, and cost-effectiveness data remain limited for many emerging nanocarrier platforms, highlighting the need for well-designed multicenter clinical trials with extended follow-up. FUTURE PERSPECTIVES The development of precision medicine is directly related to the future of drug delivery based on nanotechnology. It is anticipated that new smart nanoparticles that can react to pH, temperature, enzyme activity, magnetic fields, ultrasound, or light would increase therapeutic precision while reducing side effects. By optimising physicochemical characteristics, forecasting biodistribution, and customising treatment selection, artificial intelligence and machine learning may make nanoparticle design easier. Advanced nanocarriers are expected to find widespread use in gene-editing technologies such as RNA interference, messenger RNA therapies, and CRISPR-Cas systems. Promising substitutes with enhanced biocompatibility and immune evasion include biomimetic nanoparticles, exosome-based delivery methods, and hybrid nanomaterials. Simultaneous disease identification, treatment, and monitoring may be made possible by the integration of therapeutic delivery (theranostics) with diagnostic imaging. To promote safe and equitable clinical translation, future research should focus on standardised manufacturing procedures, globally harmonised regulatory frameworks, extensive randomised clinical trials, pharmacoeconomic assessments, and long-term post-marketing surveillance. In order to improve patient access to novel nanomedicines and expedite commercialisation, cooperation between academics, industry, and regulatory bodies will be essential.

Nanotechnology-based drug delivery systems represent a major advancement in targeted pharmacotherapy by overcoming many of the limitations associated with conventional drug delivery methods. The evidence compiled in this systematic review shows that nanocarriers, such as liposomes, polymeric nanoparticles, lipid nanoparticles, dendrimers, and exosome-based systems, improve drug bioavailability, facilitate controlled drug release, improve tissue-specific targeting, and lessen systemic toxicity in a variety of diseases. Nanotechnology has significantly enhanced treatment precision and clinical results in oncology, infectious diseases, neurological disorders, cardiovascular diseases, diabetes, and gene therapy.

Large-scale production, repeatability, regulatory approval, long-term biosafety, immunogenicity, and cost-effectiveness continue to be significant obstacles despite notable advancements. Addressing these constraints will require standardised characterisation methodologies, rigors clinical evidence, and multidisciplinary teamwork. The therapeutic potential of nanomedicine is anticipated to be significantly expanded by ongoing innovation in stimuli-responsive nanocarriers, biomimetic delivery systems, artificial intelligence-assisted formulation design, and gene-editing technologies.

In summary, targeted medication delivery has been completely revolutionised by nanotechnology, which is set to become more and more significant in precision medicine. With ongoing technological development and thorough clinical evaluation, nanomedicine is predicted to become a key component of future therapeutic methods, enhancing treatment efficacy, patient safety, and overall healthcare results worldwide.

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