PLGA based nanomaterials in Drug Delivery for cancer treatment: Innovations and Emerging Applications

Abstract

Poly (lactic-co-glycolic acid) (PLGA) has emerged as a cornerstone in modern drug delivery systems (DDSs), offering unparalleled biodegradability, biocompatibility, and tunable drug release kinetics. This review highlights the latest innovations and emerging applications of PLGA in drug delivery, focusing on its role in cancer therapy, neurological disorders, pain management, inflammation, vaccines, and tissue regeneration. Recent advancements in PLGA-based systems, such as stimuli-responsive carriers, targeted delivery strategies, and combination therapies, have significantly enhanced therapeutic efficacy while minimizing systemic toxicity. Despite its success, challenges like burst release, batch-to-batch variability, and regulatory hurdles persist. Future directions include optimizing PLGA properties, integrating advanced technologies like 3D printing and nanotechnology, and developing personalized medicine approaches. By addressing these challenges, PLGA-based DDSs hold immense potential to revolutionize healthcare, offering precise, controlled, and patient-specific treatments for a wide range of diseases. This review underscores the transformative role of PLGA in advancing drug delivery and outlines key strategies to overcome existing limitations, paving the way for next-generation therapeutic solutions.

Keywords

PLGA, Drug Delivery Systems, Stimuli-Responsive Carriers, Targeted Delivery, Personalized Medicine, Biodegradable Polymers

Introduction

Overview of PLGA in Drug Delivery Systems (DDSs)

Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible copolymer that has emerged as a cornerstone in the development of advanced drug delivery systems (DDSs). Its unique properties, such as tunable degradation rates, controlled drug release kinetics, and excellent safety profile, make it an ideal candidate for encapsulating a wide range of therapeutic agents, including small-molecule drugs, proteins, peptides, and nucleic acids. PLGA-based DDSs have been extensively explored for their ability to enhance therapeutic efficacy, reduce systemic toxicity, and improve patient compliance. These systems are particularly advantageous for drugs with narrow therapeutic windows, poor bioavailability, or those requiring sustained release over extended periods. The versatility of PLGA allows it to be formulated into various delivery platforms, such as nanoparticles, microparticles, implants, and micelles, catering to diverse clinical needs.

Historical Development and Significance of PLGA

The development of PLGA dates back to the 1970s when it was first synthesized as a biodegradable polymer for surgical sutures. Over the decades, its application expanded into the pharmaceutical field, particularly in drug delivery. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved PLGA for use in several drug products, underscoring its safety and efficacy. The first FDA-approved PLGA-based drug delivery product, Lupron Depot® (leuprolide acetate), was introduced in 1989 for the treatment of prostate cancer and endometriosis. Since then, PLGA has been utilized in numerous FDA-approved products, including Risperdal Consta® (risperidone) for schizophrenia and Vivitrol® (naltrexone) for opioid dependence. The historical significance of PLGA lies in its ability to revolutionize drug delivery by enabling long-acting, controlled-release formulations that reduce dosing frequency and improve therapeutic outcomes.

Scope and Objectives of the Review

This review aims to provide a comprehensive overview of the recent advancements and emerging applications of PLGA in drug delivery. The scope encompasses the physicochemical properties of PLGA, innovative formulation strategies, and its application in treating various diseases, including cancer, neurological disorders, pain, inflammation, and infectious diseases. Additionally, the review highlights the challenges associated with PLGA-based DDSs, such as burst release, batch-to-batch variability, and acidic degradation by-products. The objectives are to:

1. Explore the fundamental properties of PLGA that make it suitable for drug delivery.
2. Discuss recent innovations in PLGA-based DDSs, including targeted and stimuli-responsive systems.
3. Examine the emerging applications of PLGA in healthcare, from vaccines to tissue regeneration.
4. Address the limitations and future directions for optimizing PLGA-based drug delivery. ^[1,2]

Table 1 Key Milestones in the Development of PLGA-Based Drug Delivery Systems

Year	Milestone	Significance
1970s	Synthesis of PLGA for surgical sutures	First application of PLGA as a biodegradable material.
1989	FDA approval of Lupron Depot® (leuprolide acetate)	First PLGA-based long-acting injectable for prostate cancer and endometriosis.
2003	FDA approval of Risperdal Consta® (risperidone)	PLGA microspheres for schizophrenia treatment.
2010	FDA approval of Vivitrol® (naltrexone)	PLGA microspheres for opioid and alcohol dependence.
2020s	Development of stimuli-responsive and targeted PLGA systems	Enhanced precision and efficacy in drug delivery.

Table 2 Advantages and Challenges of PLGA in Drug Delivery

Aspect	Advantages	Challenges
Biodegradability	Breaks down into non-toxic byproducts (lactic acid and glycolic acid).	Acidic degradation byproducts may cause tissue irritation.
Controlled Release	Tunable degradation rates for sustained drug release.	Initial burst release can lead to inconsistent drug levels.
Versatility	Can be formulated into nanoparticlemicroparticles, implants, and micelles.	Batch-to-batch variability affects reproducibility.
Biocompatibility	Safe for use in humans, approved by FDA and EMA.	Limited drug-loading capacity for certain therapeutics.
Targeted Delivery	Surface modification enables active targeting to specific tissues or cells.	Complex manufacturing processes increase production costs.

Table 3 Emerging Applications of PLGA in Drug Delivery

Application	Description	Example
Cancer Therapy	PLGA nanoparticles for targeted chemotherapy and photothermal therapy.	Paclitaxel-loaded PLGA nanoparticles for breast cancer.
Neurological Disorders	PLGA carriers for crossing the blood-brain barrier (BBB).	Mannose-coated PLGA nanoparticles for Alzheimer’s disease.
Pain Management	Long-acting PLGA formulations for local anesthetics.	Ropivacaine-loaded PLGA microspheres for postoperative pain.
Vaccines	Single-dose PLGA-based vaccines for sustained immune response.	PLGA microparticles for influenza vaccines.
Tissue Regeneration	PLGA scaffolds for bone and cartilage repair.	PLGA-based 3D-printed scaffolds for bone regeneration.

Fundamentals of PLGA

Chemical Structure and Synthesis of PLGA

PLGA is a copolymer composed of two monomers: lactic acid (LA) and glycolic acid (GA). The ratio of these monomers can be varied to tailor the polymer's properties, such as degradation rate and mechanical strength. The synthesis of PLGA can be achieved through two primary methods: Ring-Opening Polymerization (ROP) and Direct Polycondensation.

• Ring-Opening Polymerization (ROP): ROP is the most common method for synthesizing PLGA. It involves the polymerization of cyclic dimers of lactic acid (lactide) and glycolic acid (glycolide) in the presence of a catalyst, such as tin (II) bis(2-ethylhexanoate) (Sn (Oct)?). This method allows precise control over the molecular weight and monomer ratio, resulting in polymers with consistent properties. The process yields PLGA with hydroxyl or carboxyl end groups, depending on the initiator used.
• Direct Polycondensation: Direct polycondensation involves the direct reaction of lactic acid and glycolic acid monomers under heat and vacuum to remove water as a by-product. While this method is simpler, it often results in lower molecular weight polymers and less control over the monomer sequence distribution compared to ROP. ^[3]

Biodegradation Mechanisms of PLGA

PLGA degrades through hydrolysis of its ester bonds, leading to the breakdown of the polymer into lactic acid and glycolic acid, which are metabolized via the Krebs cycle and excreted as carbon dioxide and water.

• Hydrolysis and Erosion: PLGA degradation occurs in four stages:
  1. Hydration: Water penetrates the polymer matrix, disrupting hydrogen bonds.
  2. Initial Degradation: Ester bonds are cleaved, reducing molecular weight.
  3. Constant Degradation: Autocatalysis by carboxylic end groups accelerates degradation.
  4. Solubilization: Polymer fragments dissolve into smaller molecules, leading to complete degradation.
• Degradation Products and Metabolic Pathways: The degradation products, lactic acid and glycolic acid, are metabolized in the body. Lactic acid enters the Krebs cycle and is converted into pyruvate, while glycolic acid is either excreted in urine or oxidized to glyoxylate, which is further metabolized. These pathways ensure minimal systemic toxicity. ^[4]

Physicochemical Properties of PLGA

The properties of PLGA are influenced by its molecular weight, monomer ratio, blockiness, and end-capping.

• Molecular Weight and Intrinsic Viscosity: PLGA's molecular weight (ranging from 10,000 to 200,000 g/mol) affects its degradation rate and drug release kinetics. Higher molecular weight PLGA degrades more slowly, providing sustained drug release. Intrinsic viscosity, which correlates with molecular weight, influences particle size and encapsulation efficiency.
• Monomer Ratio (Lactic Acid to Glycolic Acid): The ratio of lactic acid to glycolic acid (e.g., 50:50, 75:25) determines the polymer's hydrophilicity and degradation rate. A higher glycolic acid content increases hydrophilicity, leading to faster degradation and drug release.
• Blockiness and End-Capping: Blockiness refers to the sequence of lactic and glycolic acid units in the polymer chain. Random copolymers degrade faster than block copolymers. End-capping (e.g., ester or acid end groups) also influences degradation, with acid-capped PLGA degrading faster due to increased hydrophilicity. ^[5]

Table 4 Comparison of PLGA Synthesis Methods

Parameter	Ring-Opening Polymerization (ROP)	Direct Polycondensation
Control Over MW	High	Low
Monomer Sequence	Controlled	Random
End Groups	Hydroxyl or carboxyl	Hydroxyl
Catalyst Required	Yes (e.g., Sn(Oct)?)	No
Complexity	High	Low

Table 5 Stages of PLGA Degradation

Stage	Description
Hydration	Water penetrates the polymer matrix, disrupting hydrogen bonds.
Initial Degradation	Ester bonds are cleaved, reducing molecular weight.
Constant Degradation	Autocatalysis by carboxylic end groups accelerates degradation.
Solubilization	Polymer fragments dissolve into smaller molecules, leading to complete degradation.

Table 6 Influence of PLGA Properties on Drug Delivery

Property	Impact on Drug Delivery
Molecular Weight	Higher MW: Slower degradation, sustained release. Lower MW: Faster degradation.
Monomer Ratio	Higher GA content: Faster degradation and drug release.
Blockiness	Random copolymers degrade faster than block copolymers.
End-Capping	Acid-capped PLGA degrades faster than ester-capped PLGA.

Innovations in PLGA-Based Drug Delivery Systems

Nanoparticles and Microparticles

PLGA nanoparticles (NPs) and microparticles (MPs) are widely used for encapsulating drugs, proteins, and peptides. These particles offer controlled release, protection from degradation, and improved bioavailability.

• Preparation Techniques:
  • Emulsion Solvent Evaporation: A common method where PLGA is dissolved in an organic solvent, emulsified in water, and evaporated to form particles.
  • Nanoprecipitation: Involves the rapid mixing of a PLGA solution with a non-solvent, leading to spontaneous particle formation.
• Drug Loading and Release Mechanisms: Drug release from PLGA particles typically follows a biphasic pattern: an initial burst release due to surface-associated drugs, followed by sustained release as the polymer degrades. ^[6]

Targeted Drug Delivery

Targeted delivery systems enhance drug accumulation at the desired site, reducing off-target effects.

• Surface Modification and Ligand Conjugation: PLGA particles can be surface-modified with ligands (e.g., antibodies, peptides) to target specific cells or tissues. For example, mannose-coated PLGA NPs target immune cells for vaccine delivery.
• Active and Passive Targeting Strategies:
  • Passive Targeting: Relies on the Enhanced Permeability and Retention (EPR) effect, where particles accumulate in leaky tumor vasculature.
  • Active Targeting: Uses ligands to bind to receptors on target cells, enhancing cellular uptake.

Stimuli-Responsive Systems

Stimuli-responsive PLGA systems release drugs in response to specific triggers, such as pH, temperature, or redox conditions.

• pH-Responsive PLGA Carriers: These systems exploit the acidic environment of tumors or inflamed tissues to trigger drug release. For example, pH-sensitive PLGA NPs release doxorubicin in tumor microenvironments.
• Temperature-Responsive Systems: Temperature-sensitive PLGA formulations release drugs in response to hyperthermia, often induced by external stimuli like lasers.
• Redox-Responsive Delivery: Redox-sensitive PLGA systems release drugs in the presence of high glutathione levels, commonly found in cancer cells. ^[7]

Combination Therapies

PLGA-based systems enable the co-delivery of multiple therapeutic agents, enhancing treatment efficacy.

• Co-Delivery of Drugs and Genes: PLGA NPs can encapsulate both chemotherapeutic drugs and nucleic acids (e.g., siRNA) to simultaneously target cancer cells and silence oncogenes.
• PLGA in Immunotherapy: PLGA particles are used to deliver immunomodulators, such as checkpoint inhibitors, to enhance anti-tumor immune responses.^[8]

Table 7 Comparison of PLGA Particle Preparation Techniques

Technique	Advantages	Limitations
Emulsion Solvent Evaporation	High encapsulation efficiency	Requires organic solvents
Nanoprecipitation	Simple, rapid process	Limited to hydrophobic drugs

Table 8 Examples of Targeted PLGA Delivery Systems

Targeting Strategy	Example	Application
Passive Targeting	EPR effect in tumors	Cancer therapy
Active Targeting	Mannose-coated PLGA NPs	Vaccine delivery

Table 9 Stimuli-Responsive PLGA Systems

Stimulus	Mechanism	Application
pH-Responsive	Drug release in acidic environments	Tumor targeting
Temperature-Responsive	Drug release at elevated temperatures	Hyperthermia-induced therapy
Redox-Responsive	Drug release in high glutathione levels	Cancer therapy

Emerging Applications of PLGA in Drug Delivery

Cancer Therapy

PLGA-based drug delivery systems have revolutionized cancer therapy by enabling targeted and controlled delivery of chemotherapeutic agents, reducing systemic toxicity, and improving therapeutic outcomes.

• Chemotherapy Delivery: PLGA nanoparticles (NPs) and microparticles (MPs) are widely used to encapsulate chemotherapeutic drugs such as paclitaxel, doxorubicin, and cisplatin. These formulations enhance drug solubility, prolong circulation time, and enable targeted delivery to tumor sites via the Enhanced Permeability and Retention (EPR) effect. For example, paclitaxel-loaded PLGA NPs have shown improved efficacy in breast and ovarian cancer models.
• Photothermal and Photodynamic Therapy: PLGA carriers are used to deliver photothermal agents (e.g., gold nanoparticles) and photosensitizers (e.g., porphyrins) for photothermal therapy (PTT) and photodynamic therapy (PDT). These therapies use light to generate heat or reactive oxygen species, selectively destroying cancer cells while sparing healthy tissue. For instance, black phosphorus quantum dots (BPQDs) encapsulated in PLGA NPs have demonstrated effective tumor ablation in preclinical studies. ^[9]

Neurological Disorders

PLGA-based systems are being explored to overcome the challenges of delivering drugs across the blood-brain barrier (BBB) for treating neurological disorders.

• Blood-Brain Barrier (BBB) Penetration: Surface-modified PLGA NPs, such as those coated with mannose or peptides, can enhance BBB penetration via receptor-mediated transcytosis. For example, mannose-coated PLGA NPs have been used to deliver donepezil and memantine for Alzheimer’s disease.
• PLGA for Alzheimer’s and Parkinson’s Disease: PLGA NPs encapsulating curcumin or ginkgo biloba extract have shown promise in reducing amyloid plaque deposition and improving cognitive function in Alzheimer’s disease models. Similarly, PLGA-based systems are being investigated for delivering dopamine agonists and neuroprotective agents in Parkinson’s disease. ^[10]

Pain Management

PLGA-based formulations are being developed for sustained and localized delivery of analgesics, reducing the need for frequent dosing and minimizing side effects.

• Local Anesthetic Delivery: PLGA MPs and NPs encapsulating local anesthetics like ropivacaine and bupivacaine provide prolonged pain relief post-surgery. For example, ropivacaine-loaded PLGA MPs have shown sustained analgesic effects in neuropathic pain models.
• Long-Acting Analgesic Formulations: PLGA-based in situ gels and implants are being developed for long-acting pain management. These systems release analgesics over weeks to months, improving patient compliance and reducing opioid dependence. ^[11]

Inflammation and Autoimmune Diseases

PLGA-based systems are being used to deliver anti-inflammatory drugs for treating chronic inflammatory and autoimmune diseases.

• Anti-Inflammatory Drug Delivery: PLGA MPs encapsulating drugs like dexamethasone and tetramethylpyrazine (TMP) have been used to treat osteoarthritis and rheumatoid arthritis. These formulations reduce inflammation and cartilage degradation while minimizing systemic side effects.
• PLGA in Rheumatoid Arthritis and Osteoarthritis: PLGA NPs loaded with anti-inflammatory agents (e.g., diclofenac) and disease-modifying drugs (e.g., methotrexate) are being explored for targeted delivery to inflamed joints, improving therapeutic outcomes.

Vaccines and Immunotherapy

PLGA-based systems are being used to develop single-dose vaccines and cancer immunotherapies, enhancing immune responses and reducing dosing frequency.

• Single-Dose Vaccines: PLGA MPs encapsulating antigens and adjuvants provide sustained release, mimicking multiple booster doses in a single administration. For example, PLGA-based influenza vaccines have shown long-lasting immune responses in preclinical studies.
• PLGA in Cancer Immunotherapy: PLGA NPs are being used to deliver immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) and cancer vaccines, enhancing anti-tumor immune responses. For instance, PLGA NPs co-loaded with antigens and adjuvants have shown potent anti-tumor effects in melanoma models. ^[12]

Tissue Regeneration and Wound Healing

PLGA-based scaffolds and NPs are being used to promote tissue regeneration and wound healing.

• PLGA Scaffolds for Bone and Cartilage Regeneration: 3D-printed PLGA scaffolds loaded with growth factors (e.g., BMP-2) and stem cells are being used to regenerate bone and cartilage in critical-sized defects. These scaffolds provide structural support and controlled release of bioactive agents.
• PLGA in Skin Wound Healing: PLGA NPs encapsulating growth factors (e.g., VEGF) and anti-inflammatory agents (e.g., curcumin) are being used to accelerate wound healing and reduce scarring. For example, curcumin-loaded PLGA NPs have shown enhanced wound closure in diabetic wound models. ^[13]

Table 10 PLGA-Based Cancer Therapy Applications

Application	Example
Chemotherapy Delivery	Paclitaxel-loaded PLGA NPs for breast cancer.
Photothermal Therapy	BPQDs/PLGA NPs for tumor ablation.
Photodynamic Therapy	Porphyrin-loaded PLGA NPs for selective cancer cell destruction.

Table 11 PLGA-Based Neurological Applications

Application	Example
BBB Penetration	Mannose-coated PLGA NPs for Alzheimer’s disease.
Alzheimer’s Disease	Curcumin-loaded PLGA NPs for amyloid plaque reduction.
Parkinson’s Disease	Dopamine agonist-loaded PLGA NPs for sustained delivery.

Table 12 PLGA-Based Pain Management Systems

Application	Example
Local Anesthetic Delivery	Ropivacaine-loaded PLGA MPs for postoperative pain.
Long-Acting Analgesics	PLGA in situ gels for sustained pain relief.

Table 13 PLGA-Based Anti-Inflammatory Applications

Application	Example
Osteoarthritis	TMP-loaded PLGA MPs for cartilage protection.
Rheumatoid Arthritis	Methotrexate-loaded PLGA NPs for targeted joint delivery.

Table 14 PLGA-Based Vaccine and Immunotherapy Applications

Application	Example
Single-Dose Vaccines	PLGA MPs for influenza vaccines.
Cancer Immunotherapy	PLGA NPs co-loaded with antigens and adjuvants for melanoma.

Table 15 PLGA-Based Tissue Regeneration Applications

Application	Example
Bone Regeneration	3D-printed PLGA scaffolds with BMP-2.
Wound Healing	Curcumin-loaded PLGA NPs for diabetic wound healing.

Challenges and Limitations of PLGA-Based DDSs

Burst Release and Inconsistent Drug Release Profiles

One of the major challenges with PLGA-based systems is the initial burst release of drugs, which can lead to toxic side effects. Additionally, inconsistent drug release profiles can compromise therapeutic efficacy.

Batch-to-Batch Variability and Scalability Issues

PLGA synthesis and formulation often suffer from batch-to-batch variability, affecting reproducibility. Scaling up production while maintaining consistent quality remains a significant challenge.

Acidic Degradation Byproducts and Tissue Irritation

The acidic byproducts (lactic acid and glycolic acid) generated during PLGA degradation can cause local tissue irritation and inflammation, limiting its use in certain applications.

Limited Drug-Loading Capacity and Stability

PLGA has a limited capacity to encapsulate hydrophobic drugs, and the stability of encapsulated drugs can be compromised during storage or degradation.

Regulatory and Manufacturing Challenges

The complex manufacturing processes and stringent regulatory requirements for PLGA-based products increase production costs and delay commercialization. ^[14–17]

Table 16 Challenges in PLGA-Based Drug Delivery

Challenge	Impact
Burst Release	Initial overdose and inconsistent drug levels.
Batch Variability	Affects reproducibility and quality control.
Acidic Byproducts	Causes tissue irritation and inflammation.
Drug-Loading Capacity	Limits encapsulation of hydrophobic drugs.
Regulatory Hurdles	Increases production costs and delays commercialization.

Future Perspectives

Optimization of PLGA Properties for Enhanced Drug Delivery

The future of PLGA-based drug delivery lies in optimizing its physicochemical properties to achieve better control over drug release kinetics, improve drug-loading capacity, and enhance biocompatibility. Key areas of focus include:

• Molecular Weight Tuning: Developing PLGA polymers with precise molecular weights to tailor degradation rates and drug release profiles.
• Monomer Ratio Adjustment: Fine-tuning the lactic acid to glycolic acid ratio to balance hydrophilicity and degradation rates for specific applications.
• End-Capping Strategies: Exploring novel end-capping techniques to modulate degradation and reduce acidic byproduct-induced tissue irritation.

Development of Smart Stimuli-Responsive Systems

Stimuli-responsive PLGA systems are poised to revolutionize drug delivery by enabling site-specific and on-demand drug release. Future advancements include:

• pH-Responsive Systems: Designing PLGA carriers that release drugs in response to the acidic microenvironment of tumors or inflamed tissues.
• Temperature-Responsive Systems: Developing PLGA formulations that release drugs in response to hyperthermia, often induced by external stimuli like lasers.
• Redox-Responsive Systems: Creating PLGA carriers that release drugs in the presence of high glutathione levels, commonly found in cancer cells.

Integration with Advanced Technologies (e.g., 3D Printing, Nanotechnology)

The integration of PLGA with advanced technologies will enable the development of next-generation drug delivery systems:

• 3D Printing: Using 3D printing to fabricate PLGA scaffolds with precise geometries for tissue engineering and regenerative medicine.
• Nanotechnology: Combining PLGA with nanomaterials (e.g., gold nanoparticles, quantum dots) to create multifunctional systems for imaging and therapy.
• Microfluidics: Leveraging microfluidic techniques to produce uniform PLGA particles with controlled size and drug-loading properties.

Personalized Medicine and Precision Drug Delivery

PLGA-based systems are well-suited for personalized medicine, where treatments are tailored to individual patient needs. Future directions include:

• Patient-Specific Formulations: Developing PLGA formulations with customized drug release profiles based on patient-specific factors (e.g., disease stage, genetic makeup).
• Targeted Delivery: Enhancing the precision of PLGA-based systems by incorporating biomarkers and targeting ligands for specific tissues or cells.
• Real-Time Monitoring: Integrating PLGA carriers with sensors for real-time monitoring of drug release and therapeutic efficacy.

Overcoming Regulatory and Manufacturing Hurdles

To fully realize the potential of PLGA-based drug delivery, it is essential to address regulatory and manufacturing challenges:

• Standardization: Establishing standardized protocols for PLGA synthesis, characterization, and quality control to ensure batch-to-batch consistency.
• Scalability: Developing scalable manufacturing processes to meet the growing demand for PLGA-based products.
• Regulatory Compliance: Streamlining regulatory pathways to accelerate the approval of PLGA-based drug delivery systems. ^[18–21]

Table 17 Optimization Strategies for PLGA Properties

Property	Optimization Strategy	Impact
Molecular Weight	Precise control during synthesis	Tailored degradation and drug release rates
Monomer Ratio	Adjust lactic acid to glycolic acid ratio	Balanced hydrophilicity and degradation rates
End-Capping	Use of novel end-capping techniques	Reduced tissue irritation and controlled degradation

Table 18 Smart Stimuli-Responsive PLGA Systems

Stimulus	Mechanism	Application
pH-Responsive	Drug release in acidic environments	Tumor targeting, inflammatory diseases
Temperature-Responsive	Drug release at elevated temperatures	Hyperthermia-induced therapy
Redox-Responsive	Drug release in high glutathione levels	Cancer therapy

Table 19 Integration of PLGA with Advanced Technologies

Technology	Application	Example
3D Printing	Fabrication of PLGA scaffolds for tissue engineering	Bone and cartilage regeneration
Nanotechnology	Multifunctional PLGA systems for imaging and therapy	Gold nanoparticle-PLGA hybrids for cancer therapy
Microfluidics	Production of uniform PLGA particles	Controlled size and drug-loading properties

Table 20 Personalized Medicine and Precision Drug Delivery

Approach	Description	Example
Patient-Specific Formulations	Customized drug release profiles based on patient-specific factors	Tailored PLGA formulations for individual cancer patients
Targeted Delivery	Incorporation of biomarkers and targeting ligands	Mannose-coated PLGA NPs for targeted vaccine delivery
Real-Time Monitoring	Integration with sensors for real-time monitoring	PLGA carriers with embedded sensors for drug release tracking

Table 21 Overcoming Regulatory and Manufacturing Challenges

Challenge	Solution	Impact
Standardization	Establishing standardized protocols	Ensures batch-to-batch consistency
Scalability	Developing scalable manufacturing processes	Meets growing demand for PLGA-based products
Regulatory Compliance	Streamlining regulatory pathways	Accelerates approval of PLGA-based drug delivery systems

CONCLUSION:

PLGA has emerged as a versatile and promising material for drug delivery, offering biodegradability, biocompatibility, and tunable physicochemical properties. Its applications span a wide range of therapeutic areas, including cancer therapy, neurological disorders, pain management, inflammation, vaccines, and tissue regeneration. Despite its advantages, challenges such as burst release, batch-to-batch variability, and regulatory hurdles must be addressed to fully realize its potential. PLGA-based drug delivery systems have revolutionized the field by enabling controlled and targeted drug release, reducing systemic toxicity, and improving patient compliance. Innovations such as stimuli-responsive systems, combination therapies, and integration with advanced technologies are paving the way for next-generation drug delivery solutions.

To advance PLGA-based drug delivery, future research should focus on:

1. Optimizing PLGA properties for enhanced drug delivery.
2. Developing smart stimuli-responsive systems for precision medicine.
3. Integrating PLGA with advanced technologies like 3D printing and nanotechnology.
4. Addressing regulatory and manufacturing challenges to accelerate commercialization.

PLGA-based nanomaterials represent a versatile and promising approach for cancer drug delivery. Their ability to improve therapeutic efficacy, reduce side effects, and enable combination therapies makes them a valuable tool in the fight against cancer. Continued research and innovation in this field are essential to overcome existing challenges and fully realize the potential of PLGA-based nanomaterials in clinical settings.

Conflict of Interest:

The author declares that there are no conflicts of interest regarding the publication of this article.

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