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Type of technology

Inorganic nanoparticles

Administration route

Subcutaneous, Intramuscular, Intravenous, Topical (Rectal), Transmucosal, Transdermal

Development state and regulatory approval

Active Pharmaceutical Ingredient (API)

C-FNP (Chemosensitizing siRNA)

Development Stage

Pre-clinical

Regulatory Approval

Not provided

Description

Fusogenic liposome-coated porous silicon nanoparticles represent a biodegradable drug delivery system for oligonucleotides, capable of bypassing endocytic pathways to facilitate direct cytoplasmic delivery. This system enables the release of the API from the nanoparticle core into the cell cytoplasm. The fusogenic liposome layer, which surrounds the silicon-based core, is functionalized with polyethylene glycol (PEG) to enhance stability and circulation time

Developer(s)

University of California
Originator
United States of America

University of California

The University of California, San Diego (UCSD), founded in 1960, is a leading research institution known for innovation in science and technology. UCSD excels in drug delivery research, focusing on nanomedicine, biomaterials, and targeted therapies. Its infrastructure includes advanced labs like the Center for Drug Discovery Innovation, fostering interdisciplinary collaborations.

Technology highlight

1. The API is encapsulated within the porous structure of the fusogenic liposomal nanoparticle. 2. The API is released into the cytoplasm through the shedding of the nanoparticle's fusogenic lipid coating, facilitating direct intracellular delivery. 3. The nanoparticle exhibits a high API loading capacity, allowing for the efficient delivery of therapeutic agents. 4. The formulation demonstrates low cytotoxicity, ensuring biocompatibility for in vitro and in vivo applications. 5. The fusogenic nanoparticles achieve 90–100% transfection efficiency due to enhanced cellular uptake through membrane fusion and endosomal escape.

Illustration(s)

Technology main components

a) Silicon-containing core b) Porous surface that is chemically linked to the core c) Plurality of cargo molecules that are physically associated with silicon-containing core material d) Metal silicate e) Fusogenic liposome coating with silicon-containing core material

Information on the raw materials sourcing, availability and anticipated price

The raw materials are obtained from Alza Corporation and Nova Pharmaceuticals.

Safety, Efficacy and Evidence Summary

Safety

Not provided

Efficacy

Not provided

Evidence Summary

Not provided

References and relevant studies

Not provided

APIs compatibility profile

API desired features
Nucleic acids

Oligonucleotides such as small interfering RNA (siRNA) therapeutics are targeted for this fugogenic nanoparticle drug delivery system. Some examples of siRNA peptides that are targeted against Irf5 gene and Rev3l gene.

Proteins

Fusogenic porous silicon nanoparticles have the capacity to securely deliver proteins to the targeted site, but the choice of protein for this delivery system is not disclosed.

Additional solubility data

Not provided

Additional stability data

Not provided

API loading: Maximum drug quantity to be loaded

75-90 wt%

API co-administration

1 single API :

LogP

Not provided

Scale-up and manufacturing prospects

Scale-up prospects

Not provided

Tentative equipment list for manufacturing

1. Teflon Etch 2. Square Wave Generator 3. Sonicator Bath 4. Liposome Extruder

Manufacturing

Fusogenic Nanoparticle Manufacturing in Small Scale includes: Etch a silicon wafer in HF using square wave currents (50 mA/cm² for 0.6 s, 400 mA/cm² for 0.36 s) for 500 cycles. Detach the porous layer (3.7 mA/cm², 250 s), rinse with ethanol and water, and store silicon chips in RNase-free water. Sonicate chips (35 kHz, 12 h). Prepare DMPC, DSPE-PEG, and DOTAP lipid film, hydrate with siRNA-loaded calcium-coated nanoparticles, and extrude 20× through a polycarbonate membrane. Conjugate targeting peptides (1 mg/mL, 20 min), purify via 30 kDa filtration, and store at -80°C.

Specific analytical instrument required for characterization of formulation

1. Dynamic Light Scattering (DLS) 2. Zeta Potential Analyzer 3. Transmission Electron Microscopy (TEM) 4. Confocal Laser Scanning Microscopy (CLSM) 5. Fourier Transform Infrared Spectroscopy (FTIR) 6. Ultraviolet-Visible Spectroscopy (UV-Vis) 7. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) 8. Differential Scanning Calorimetry (DSC) 9. Nanoparticle Tracking Analysis (NTA) 10. High-Performance Liquid Chromatography (HPLC)

Excipients & delivery device(s)

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredient Database (IID) for the specified route of administration

No novel excipient or existing excipient used

Residual solvents used

No residual solvent used

Delivery device(s)

No delivery device

Additional features

Other features of the technology
  • Biodegradable
  • Drug-eluting
Release properties

Preclinical studies show that the fusogenic lipid-coated nanoparticles have very little initial burst release rate. It also proves that up to 75% of the API is released into the cells at 168 hours and complete release after 336 hours, i.e., 14 days.

Injectability

Fusogenic porous silicon nanoparticles can be administered via intravitreal, intravenous, and subcutaneous injection.

Stability

Product Stability: Details regarding the formulation's stability are not disclosed. Nanoparticle Stability: The stability of the nanoparticles can be modified by adjusting their size to optimize the API payload.

Storage conditions and cold-chain related features

Not provided

Therapeutic area(s)

  • Other(s) : "Fibrosis, nosocomial and community acquired infections"
Use case(s)

Not provided

Potential associated API(s)

  • C-FNP (Chemosensitizing siRNA)
  • T-FNP (Immune-modulating siRNA)
  • VEGF-A (Vascular endothelial growth factor A siRNA) (VEGF-siRNA)

Use of technology

Ease of administration
  • Administered by a community health worker
  • Administered by a nurse
  • Administered by a specialty health worker
Frequency of administration

Weekly, Monthly

User acceptance
Not provided

Targeted user groups

Age Cohort
  • Adults
  • Older Adults
Genders
  • All
Pregnant individuals

Unspecified

Lactating individuals

Unspecified

Healthy individuals

Unspecified

Comment

Not provided

C-FNP (Chemosensitizing siRNA)

Class(es)

Oligonucleotides

Development stage

Pre-clinical

Clinical trial(s)

Not provided

Foreseen/approved indication(s)

Solid Tumors

Foreseen user group

Not provided

Foreseen duration between application(s)

Once weekly

Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals

Not provided

T-FNP (Immune-modulating siRNA)

Class(es)

Oligonucleotides

Development stage

Pre-clinical

Clinical trial(s)

Not provided

Foreseen/approved indication(s)

Solid Tumors

Foreseen user group

Not provided

Foreseen duration between application(s)

Once weekly

Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals

Not provided

VEGF-A (Vascular endothelial growth factor A siRNA) (VEGF-siRNA)

Class(es)

Oligonucleotides

Development stage

Pre-clinical

Clinical trial(s)

Not provided

Foreseen/approved indication(s)

Diabetic retinopathy

Foreseen user group

Not provided

Foreseen duration between application(s)

Once weekly

Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals

Not provided

Description

Fusogenic liposome-coated porous silicon nanoparticles

Brief description

The disclosure describes a fusogenic liposome-coated porous silicon nanoparticles for high loading efficiency of anionic payloads (small molecules, dyes, nucleic acids), and for non-endocytic delivery of hydrophilic and lipophilic payloads by membrane fusion. The liposome coating can be further modified with targeting peptides or antibodies via covalent binding chemistry between the ligands and functionalized poly(ethylene glycol). The surface moieties can be transferred to the cellular membrane surface by fusogenic uptake. The composition of the disclosure can be applied in the treatment of diseases by delivering entrapped/encapsulated payloads.

Representative patent

US10702474B2

Category

Formulation

Patent holder

University of California San Diego UCSD

Exclusivity

Not provided

Expiration date

July 8, 2038

Status

Anticipated expiration