DelSiTech Silica Matrix Drug Delivery

Sponsor(s)

- -

Partnerships

	Innovare r&d http://www.innovare-rd.com.mx/
	Bayer https://www.bayer.com/
	Astrazeneca https://www.astrazeneca.com/
	Visus Therapeutics https://www.visustx.com/
	The Bill & Melinda Gates Foundation https://www.gatesfoundation.org/
	UNITAID https://unitaid.org/#en

Type of technology

Silica microparticles; silica hydrogel; silica microparticles and silica hydrogel composite,, Biodegradable monolithic solid silica implant, Inorganic nanoparticles

Administration route

Subcutaneous, Intra-articular, Intramuscular, intratumoral, intraocular, intrathecal and transtympanic, Intra-vitreal, intratumoral, intraocular, intrathecal and transtympanic

Development state and regulatory approval

Entecavir (ETV)

Pre-clinical

No

Description

Long-acting injectables (parenteral administration) and topical eye drops drug delivery technology where the active substance is embedded and released in controlled manner from a biodegradable silica microparticle-silica hydrogel composite material, with release period tunable from a day to several weeks, months up to a year.

Technology highlight

DelSiTech Silica Matrix long-acting drug delivery technology is adaptable to any therapeutic agents: from small molecules to peptides and complex biologics. The technology is compatible with high API loading, but also with poorly or highly soluble molecules. True controlled release that can be tuned from days up to a year, following zero-order release profile with no or limited burst release. The final dosage form is a ready to use prefilled syringe with 24 to 30G needle. Silica microparticle-silica hydrogel depot can be easily removed as one piece in case of adverse effects. With eyedrops the release can be adjusted from 24 to 48 hours with stable API concentration even overnight with a single drop.

Technology main components

The formulation contains only one main excipient silica (SiO2). in addition, WFI (water for injection), and pH controlling agents (in the hydrogel component).

Information on the raw materials sourcing, availability and anticipated price

Tetraethyl orthosilicate (TEOS) the silica precursor is widely available material used for various application.

Delivery device(s)

No delivery device

API desired features

Not provided

Additional solubility data

Not provided

Additional stability data

APIs are stable in solid silica microparticles. There is no chemical/biological interaction with the Silica nor with external environment.

API loading: Maximum drug quantity to be loaded

30-50 wt%

API co-administration

2 different APIs : No technical limits.

LogP

Not provided

Scale-up prospects

Spray-drying process is highly scalable process and widely used.

Tentative equipment list for manufacturing

Mixer and pumping prior spray drying. Spray drying equipment. Fill and finish equipment

Manufacturing

Normal manufacturing requirements for spray drying and aseptic fill and finish.

Specific analytical instrument required for characterization of formulation

HPLC equipment, capability to perform immunoassays and the appropriate detection equipment required by the API. Dynamic light scattering (DLS) instrument for particle size distribution. Dissolution for release characteristics in water bath in shaking. Silica measurement with microwave plasma-atomic emission spectroscopy (MP-AES) or with spectrophotometric measurements. Rheometric analysis (oscillation and rotation), manual injectability and injection force measurement. SEM analysis for visualizing the particles. NMR for measuring silica condensation.

Proprietary excipients used

No proprietary excipient used

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

Can be determined with a partner. Can be introduced during clinical studies.

Residual solvents used

No residual solvent used

Other features of the technology

• Biodegradable
• Monolithic
• Removable
• Single-use
• Room temperature storage
• Other(s)

  +4 to +8 degrees Celsius storage may be needed in some cases

Release properties

Release time is adjustable: as fast as one day or as slow as one year. The release is based on surface erosion mechanic.

Injectability

Silica microparticles-hydrogel depot has shear thinning properties and can be used with pain-free needles up to 30G.

Safety

Silica is inert, non-toxic and completely bio-dissolvable. The main degradation product is soluble silicic acid that is a natural component of the body. Silica is accepted for topical use and tox tolerability data available for injectables.

Stability

The APIs is homogeneously dispersed and encapsulated in inert solid silica microparticles, maintaining high chemical stability and biological activity for the APIs

Storage conditions and cold-chain related features

Room-temperature storage if encapsulated drug does not require refrigeration

Therapeutic area(s)

Use case(s)

Use of technology

Technology patent families

Publications

<p><a href="https://pubmed.ncbi.nlm.nih.gov/28752299/" rel="noopener noreferrer" target="_blank">Silica microparticles for sustained zero-order release of an anti-CD40L antibody. </a></p><p>Tyagi P, Koskinen M, Mikkola J, Leino L, Schwarz A. </p><p>Drug Deliv Transl Res. </p><p>2018 Apr;8(2):368-374. doi: 10.1007/s13346-017-0408-1. PMID: 28752299.</p>

Silica microparticle hydrogel depot (HG) formulation was prepared using spray drying of silica-based sol-gels for the sustained delivery of MR1 antibody which binds to CD40 ligand (CD40L). The formulation was tested in vitro for antibody release, surface morphology, particle size, rheology, and injectability. In vivo pharmacokinetic evaluation was performed for the microparticle formulation and free MR1 antibody in BALB/c female mice. Serum samples up to day 62 were assessed using an enzyme-linked immunosorbent assay. In vitro release indicated that the MR1 antibody was uniformly encapsulated in silica microparticles, and less than 5% burst release of the antibody was observed. In vivo pharmacokinetics showed a zero-order release up to 62 days from the MR1 silica microparticle HG-controlled release composition.

Keywords: Antibody; Biologics; Silica microparticles; Sustained release.

<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233906/#:~:text=In%20vivo%20pharmacokinetics%20showed%20that,as%20the%20Pamorelin%C2%AE%20injections." rel="noopener noreferrer" target="_blank">Sustained In-Vivo Release of Triptorelin Acetate from a Biodegradable Silica Depot: Comparison to Pamorelin® LA</a></p><p>Nanomedicines, June 2021</p><p>Ari-Pekka Forsback, Panu Noppari, Jesse Viljanen, Jari Mikkola, Mika Jokinen, Lasse Leino, Simon Bjerregaard, Camilla Borglin and Janet Halliday </p>

Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin^® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin^® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin^® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period.

Additional documents

• Parenteral delivery of therapeutic proteins using biodegradable silica matrix - LAII2020 conference

Useful links

• Short Video presenting the technology

	Collaborate for development Consider on a case by case basis, collaborating on developing long acting products with potential significant public health impact, especially for low- and middle-income countries (LMICs), utilising the referred to long-acting technology Agree
	Share technical information for match-making assessment Provide necessary technical information to a potential partner, under confidentiality agreement, to enable preliminary assessment of whether specific medicines of public health importance in LMICs might be compatible with the referred to long-acting technology to achieve a public health benefit Agree
	Work with MPP to expand access in LMICs In the event that a product using the referred to long-acting technology is successfully developed, the technology IP holder(s) will work with the Medicines Patent Pool towards putting in place the most appropriate strategy for timely and affordable access in low and middle-income countries, including through licensing Agree

More information available at https://www.delsitech.com/