Library · Biology & lab methods

What Nanocarrier Drug Loading & Release got wrong, from 19 theses

Summary written by a model from the records below: The records describe engineering challenges in drug carrier systems, focusing on difficulties in controlling release kinetics, retaining payload integrity, and achieving sufficient drug loading. Researchers encountered issues ranging from premature leakage and incomplete cargo release to fabrication defects and poor in vivo translation. These records come from graduate theses, 2021 to 2025, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.

19
theses
13
institutions
19
failure records
4
failure modes

Plus 9 problems the authors left open, listed at the end.

Failure modes, by theses reporting them

Select a mode to jump to its records.

Excessively slow or incomplete cargo release impairs therapeutic efficacy
6
6 theses · 5 institutions · 6 records
Premature leakage and uncontrolled burst release compromise carrier stability
6
6 theses · 5 institutions · 6 records
Unfavorable release mechanisms and poor in vivo translation limit carrier designs
5
5 theses · 3 institutions · 5 records
Insufficient loading capacity and surface binding prevent functional delivery
2
2 theses · 2 institutions · 2 records

Excessively slow or incomplete cargo release impairs therapeutic efficacy

6 theses · 5 institutions

Drug carriers frequently suffered from impeded release rates, with formulations like polycaprolactone nanofibers and printed tablets yielding incomplete cumulative release compared to benchmark systems. In other instances, excessive hydrophobicity, intermediate charge ratios, or dense polymer geometry prevented timely payload diffusion and reduced drug potency.

Lost to a baseline

PGC-PTX + PTX NPs had higher in vitro IC50 values (14.1 to 67.2 ng/mL) across mesothelioma cell lines compared to free PTX (1-10 ng/mL) due to slow sustained drug release.

Design, formulation, characterization, and evaluation of polymeric nanoparticles for local chemotherapy · Boston University · PhD

Lost to a baseline

PEG 8000–fenofibrate eutectic printed tablets released only 69% drug after 120 min, whereas prior powdered eutectic formulations in capsules achieved ~100% release after 60 min.

Formulation strategies for the 3D extrusion printing of tablets containing a poorly soluble drug · Nottingham · Doctorate

Lost to a baseline

Curcumin-loaded Poly ε-Caprolactone nanofibers reached only ~50% cumulative release after 30 days, compared to other polymer systems reaching almost 100%.

Curcumin as endometriosis treatment: efficacy, drawbacks, and future perspectives · Boston University · Master's

Considered and rejected

Considered and rejected: Rejected longer ω-carboxyalkanoate linkers (adipate or longer via benzyl-protected acid chlorides or cross-metathesis) because excessive hydrophobicity caused polymers to swell without dissolving, yielding poor drug release.

Mixed Polysaccharide Esters for Amorphous Solid Dispersion Oral Drug Delivery Vehicles · Virginia Tech · Doctorate

Tried and failed

intermediate charge ratio complexation in lipid nanoparticles applied to siRNA delivery and gene silencing. Outcome: worse than baseline. Reason: intermediate charge ratios exhibited slowest release kinetics, reducing downregulation efficacy

Lipid-based nanoparticles for drug delivery · UT Austin · Doctorate

Lost to a baseline

3D-printed IR tablets slightly missed USP criterion (≥80% release within 30 min) due to high compactness and full body infill, whereas commercial IR achieves it.

Investigating Pharmaceutical 3D Printing: From Process Assessment to Product Characteristics · Tübingen · PhD

Premature leakage and uncontrolled burst release compromise carrier stability

6 theses · 5 institutions

Formulations experienced rapid cargo loss when high drug loading, permeable membranes, or lack of charge complexation caused premature payload leakage before reaching target sites. Similarly, coating-induced nanoparticle agglomeration, plasma instability, and single wall materials triggered rapid release and degraded encapsulation efficiency.

Considered and rejected

Considered and rejected: 80% sirolimus nanofiber loading target was rejected in favor of 40% loading due to a pronounced burst release occurring within the first 24 h.

ENGINEERING NANOSTRUCTURED MEDICAL DEVICES AND FORMULATIONS FOR IMPROVING SURGICAL OUTCOMES · Johns Hopkins · PhD

Considered and rejected

Considered and rejected: Rejected using single wall material (such as maltodextrin alone) due to quick gastrointestinal release, deficient emulsification, and lower encapsulation efficiency.

Dietary supplementation of haskap berry (Lonicera caerulea L.) anthocyanin-rich fraction and probiotics attenuates the severity of dextran sulfate sodium-induced acute colitis in Balb/C mice · Dalhousie · Master's

Tried and failed

direct liposomal encapsulation without charge complexation applied to pore-forming antimicrobial peptides. Reason: failed to prevent membrane lytic activity and leakage prior to intended release

Activity-based molecular circuits for programmable medicine · Georgia Tech · PhD

Tried and failed

polysaccharide surface coating for controlled release applied to mesoporous inorganic nanoparticles. Outcome: unstable. Reason: coating induced nanoparticle agglomeration and triggered non-selective burst release of loaded ions

Inorganic nanoparticles for cancer therapy · Imperial · PhD

Tried and failed

in situ albumin-binding maleimide prodrug delivery applied to cytotoxic drug delivery. Outcome: unstable. Reason: rapid premature payload release in plasma compared to preformed ex vivo conjugates

Albumin as a drug delivery carrier to overcome biological barriers in cancer · UT Austin · PhD

Considered and rejected

Considered and rejected: Rejected using dendrimersomes as nanocarriers for small hydrophilic drug retention due to inherent membrane semipermeability to small molecules (<600 Da).

Self-assembled vesicular nanostructures for bacterial applications · Imperial · PhD

Unfavorable release mechanisms and poor in vivo translation limit carrier designs

5 theses · 3 institutions

Several polymeric systems were rejected because their non-linear degradation, rapid clearance, or diffusion-driven profiles failed to match desired release timing and surface erosion. Additionally, surface modifications that appeared sustained in vitro failed to prevent rapid clearance in vivo, while certain lipid mixtures showed deficient responsiveness to triggers.

Tried and failed

block copolymer blending for erosion rate acceleration applied to polymeric core-shell microparticle cap. Outcome: worse than baseline. Reason: Block copolymer blending did not accelerate release timing compared to physically doping homopolymer.

Microscale polymeric-based technologies for controlled vaccine delivery · MIT · PhD

Considered and rejected

Considered and rejected: Binary liposome compositions BSM:CH (50:50 wt%) and PC:CH (50:50 wt%) were rejected in favor of the ternary BPC formulation (BSM:PC:CH 33:33:33 wt%) due to lower toxin-triggered release responsiveness

Engineering catalytic gold nanoclusters and nanovesicles for detection of disease · Imperial · PhD

Considered and rejected

Considered and rejected: Rejected bulk-degrading polymer micro/nanoparticles, gels, and films due to non-linear release, loss of mechanical integrity preventing retrieval, and rapid lymphatic clearance

Chemotherapy-Eluting Intraperitoneal Implants for Advanced Stage Ovarian Cancer Treatment · MIT · PhD

Tried and failed

surface modification for sustained drug release applied to mesoporous biomaterial vaccine delivery systems. Outcome: did not generalise. Reason: in vitro release kinetics failed to predict in vivo rapid clearance indistinguishable from unmodified controls

Developing strategies to enhance immune responses induced by mesoporous silica rod vaccines · Harvard · PhD

Considered and rejected

Considered and rejected: Amphiphilic block copolymers (PLGA, PEG) and cellulosic polymers (HPMC) were rejected as primary carriers because release is diffusion-driven rather than surface-eroding.

Intratumoral, multiplexed and polymer-assisted dosing of drugs as a new method for assessment of efficacy of new oncology drug candidates or drug combinations. · Harvard · Master's

Insufficient loading capacity and surface binding prevent functional delivery

2 theses · 2 institutions

Carriers frequently failed to load or deliver adequate amounts of functional genetic material to elicit biological activity. Formulations were abandoned because released concentrations were too low to reach functional doses without aggregation, surface layering fell short of required charge ratios, or unfunctionalized surfaces failed to bind nucleic acids.

Considered and rejected

Considered and rejected: Rejected 2nd gen sequential layering of P10PSH copolymer onto preformed AuNP-RNP because maximum polymer loading achieved only N/P 0.5, insufficient for endosomal escape.

Development of Third-Generation Gold Nanoparticles (CRISPR-AuNP) for Enhanced CRISPR Delivery to Hematopoietic Stem and Progenitor Cells · University of Washington · PhD

Tried and failed

unfunctionalized vertical nanostructures for intracellular delivery applied to nucleic acid transfection in primary immune cells. Outcome: no signal. Reason: lack of surface charge or functionalization prevented effective nucleic acid binding and intracellular release

ENGINEERING MATERIALS FOR IMMUNOMODULATION · Cornell · PhD

Left open by the authors

Problems the authors named and did not get to.

Left open

Model drug delivery mechanisms including aerosol flow rate, delivered volume, payload release kinetics, and environmental interactions within the nanoparticle selection framework. Blocker: None

Design Tool Used for the Selection of Nanoparticle Drug Delivery Systems in the Treatment of Respiratory Diseases · Harvard · Master's

Left open

Optimize CHIR99021 dosage and encapsulate it using nanoparticles, liposomes, or bioink conjugation for sustained controlled release. Blocker: Requires wet lab facilities for nanoparticle/liposome formulation, drug conjugation, and release kinetics assays.

3D Bioprinting of Perfusable Cardiac Patches to Treat Myocardial Infarction · Georgia Tech · PhD

Left open

Conduct in vivo and stimuli-responsive release testing of therapeutic cargo and MRI contrast agents from functionalised Type II nanogels. Blocker: Requires wet lab synthesis, biological materials, and in vivo animal testing facilities

Molecular and nanoscale agents for magnetic resonance imaging · Imperial · PhD

Left open

Quantify in vitro release kinetics of resveratrol encapsulated within donkey and bovine beta-casein micelles. Blocker: Requires wet lab equipment, purified beta-casein, and dialysis/chromatography apparatus for release assays

Encapsulation of bioactive nutraceutical compounds in donkey and bovine milk β-casein-based carriers · University of Camerino · PhD

Left open

Test in vivo whether higher re-loading doses of free PROTAC enable non-covalent ADC re-loading in circulation. Blocker: Requires in vivo animal experiments and specialized wet lab facilities

Noncovalent PROTAC Antibody Drug Conjugates · MIT · PhD

Left open

Assess transported PDF models, beta-PDF intermittency factor corrections, or LES subfilter closures against the reacting jet DNS dataset. Blocker: Requires access to the proprietary or unreleased DNS flow field dataset generated in the thesis.

A reacting jet direct numerical simulation for assessing combustion model error · UT Austin · PhD

Left open

Develop and synthesize dendrimer-based nanomodulators targeting CXCR4 to encapsulate and release SDF-1α or AMD-3100. Blocker: Requires a wet chemistry and biomaterials laboratory to synthesize dendrimers and test drug release kinetics.

Evaluating Migration of Human Monocytes in an Inflammatory Environment Mimicking Burn-Induced Inflammation in Blood Donor Samples · Harvard · Master's

Left open

Test non-pH responsive, PBS-soluble anticancer drugs for encapsulation and release in pH-responsive methacrylic polymersomes. Blocker: Requires a wet chemistry and biology lab to synthesize polymersomes and perform drug encapsulation/release assays

Self-assembled block copolymers: micelles, polymersomes and gels · Imperial · PhD

Left open

Synthesize pH-responsive nanogels incorporating an enzyme-degradable peptide crosslinker (such as MMRRRKK) to enhance protein release in the small intestine. Blocker: Requires wet lab chemical synthesis (inverse emulsion polymerization) and biological degradation testing

Itaconic acid-based pH-responsive nanoscale hydrogels for the oral delivery of high isoelectric point proteins · UT Austin · PhD

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