Brevetti+ 2019

 

Eng4Life Srl is the owner of two patents “Production of highly bioavailable iron-encapsulating nano-liposomal carriers with continuous technique” and “Continuous process for the polymeric coating of liposomal carriers” in 2020 and 2021 these patents were subject to economic enhancement thanks to the financial support from the incentive for the economic enhancement of patents, promoted by the Ministry of Economic Development and managed by Invitalia Brevetti+ 2019 – AXIS 1 Investment priority 1b Action 1.1.2.

 

In detail.

Brevetti+ support for the patent: Production of highly bioavailable iron-encapsulating nano-liposomal vectors with continuous technique

The invention process object of the patent “Production of highly bioavailable iron nano-liposomal carriers with continuous technique” (n ° 10201700009962), realizes a contact between two flows, on the one hand the phospholipids, preferably consisting of phosphatidylcholine and cholesterol, in alcoholic solution, and on the other hand, according to the invention, an aqueous solution containing iron (Fe (II)). The contact takes place inside a tubular device in which interdiffusion phenomena between the two phases cause the formation of nanometric lipid vesicles, containing the salt of Fe (II) in association with the reducing compound. The invention aims to overcome the limitations of the most used techniques for the production of liposomes. These techniques require long times and high energies, high costs of microfabrication of the implant devices and low productivity. In order to overcome these limitations, the innovation object of the patent application has transposed the microfluidic techniques, of recent literature, to a millimeter scale, called microfluidic-like, an intermediate scale between the microfluidic and macrofluidic ones. In particular, the invention consists in the design and development of a simple device suitable for a massive production of nanoliposomes, which allows to overcome the limits imposed by the previous devices. The equipment and devices that can be used for a microfluidic-like process are more common and less expensive than those needed for microfluidics, and the production flow rates involved in microfluidics are higher than those of microfluidics, allowing to work with a high control of the operating conditions consequent to the laminar motion regime.

Purpose

The industrial interest of a highly bioavailable (by association with ascorbic acid) iron-containing carrier II and stable by inclusion in nanoliposomes which, among other things, mask the unwanted taste of iron is extremely high. Therefore it would be desirable to transpose as quickly as possible the idea covered by the patent, already implemented and tested on a laboratory scale, towards the production scale. The innovation consisting in the microfluidic-like technique, which combines the advantages of microfluidics (accurate control of process conditions, production of nanoliposomes of the desired functional characteristics), with the advantages of the macroscopic scale (massive productions), will allow to produce the designed vectors, that is, nanoliposomes, with the desired load, in industrially relevant quantities, after the scale-up of the invented process, and tested on a laboratory scale.

 

Expected results

 

The strategy to be pursued to achieve industrial production involves the following steps:

  1. Acquisition of the ownership of the Italian patent application by the university spin-off Eng4Life srl, an innovative start-up. In fact, the ownership at the moment belongs to Prof. Ing. Anna Angela Barba, who is part of the inventors and is a partner in the spin-off and is obviously willing to sell it. The regulatory reference is art. 6, paragraph 1, letter c, number vi. of the Call (DD 26/11/2019).
  2. Realization of a prototype on a pre-pilot scale, capable of much higher productions than the laboratory set-up. The scale-up criteria for the new technology have been identified by the university research group that corresponds to the shareholding of the university spin-off, now it will be necessary to design and build the prototype (engineering), also making use of external professionals (electronic engineers, capable of automating the prototype, in view of the industrial application).
  3. Search for an industrial partner for the production and distribution of the nutraceutical product (liposomal suspension containing iron II and ascorbic acid). In doing this, the support of expert consultants in the defense of intellectual property will obviously be necessary to carry out those specific activities of technology transfer such as the preparation of secrecy and patent licensing agreements. The implementation of this strategy will bring the idea behind the patent to the industrial production of an iron II food supplement, highly attractive for the national and international market.

 

Accomplished results

The following results were achieved:

  1. Acquisition of the ownership of the Italian patent application by the university spin-off Eng4Life srl, an innovative start-up. .
  2. Realization of a prototype on a pre-pilot scale, capable of much higher productions than the laboratory set-up.
  3. Preparation of confidentiality and patent licensing agreements, in order to facilitate the search for an industrial partner for the production and distribution of the nutraceutical / pharmaceutical product.

 

Financial support: € 99,812.35

 

Brevetti+ support for the patent: Continuous process for the polymer coating of liposomal vectors

 

The invention covered by the patent “Continuous process for the polymeric coating of liposomal vectors” (No. 102018000002631), concerns a process for the polymeric coating of liposomal nano-vectors with a continuous, and therefore rapid, high-productivity technique. Through this process we aim to obtain nanoliposomes perfectly coated with chitosan, a natural biocompatible polymer designed to increase the stability of the nanostructures and the mucoadhesiveness. The invention makes use of the “microfluidic-like” technique, conceived by Eng4Life and the subject of a previous patent application, with high productivity for the formation of nanoliposomes, coupled with ultrasounds for the homogenization of the nanoliposomes obtained. The production method allows to obtain nanoliposomes with an average size lower than or equal to 100nm and characterized by a low polydispersivity index. In the invention, a new method of polymeric coating of liposomes was devised which uses a similar microfluidic device for the massive production of polymer-lipid particles, consisting of liposomes uniformly coated with chitosan. The technique proposed according to the invention is based on the contact between two streams: a suspension of nanoliposms, previously produced, and a chitosan solution, respectively fed by two volumetric pumps. It has been found that in these conditions the meeting between two phases, one consisting of nanoliposomes in hydroalcoholic suspension and the other consisting of an acidulous aqueous solution containing chitosan, produces nanometric-sized structures uniformly coated with polymer. The flow rates and dimensions of the selected pipes play a key role in the production of stable and perfectly polymer-coated liposomal systems, and ensure that the fluids always flow in a laminar flow regime. These fluid-handling conditions allow a continuous and uniform interaction between equal volumes of liposomes and chitosan, overcoming the limitations of discontinuous techniques. With the proposed invention, nanostructures covered with chitosan are obtained, of medium size and with a low polydispersivity index, therefore homogeneous in size.

Purpose

The idea behind the patent proposal, the production of liposomes to be used as carriers of molecules of nutraceutical / pharmaceutical interest, both lipophilic and hydrophilic, coupled to the coating of the liposomes with a biocompatible and highly bioadhesive polymer such as chitosan, is of great application interest. In fact, these vectors would be able to adhere to the mucous membranes (for example buccal ones), prolonging the release time of the active molecules and maximizing the effectiveness of the administration. Thinking for example of a sublingual administration, the problems of intravenous (poor compliance) or oral (high dosage to overcome the first pass effect) administration would in fact be overcome. The industrial interest of the product covered by the patent is therefore very high. Therefore it would be desirable to transpose as quickly as possible the idea covered by the patent, already implemented and tested on a laboratory scale, towards the production scale. The innovation consisting in the microfluidic-like technique, which combines the advantages of microfluidics (accurate control of process conditions, production of nanoliposomes of the desired functional characteristics), with the advantages of the macroscopic scale (massive productions), will allow to produce the designed vectors, with the desired load, in industrially relevant quantities, after the scale-up of the invented process, and tested on a laboratory scale.

 

Expected results

  1. The strategy to be pursued to reach industrial production involves the following steps: 1. Realization of a prototype on a pre-pilot scale, capable of much higher productions than the laboratory set-up. The scale-up criteria for the new technology have been identified by the university research group that corresponds to the shareholding of the university spin-off, now it will be necessary design and build the prototype (engineering), also making use of external professionals (electronic engineers, capable of automating the prototype, in view of industrial application).
  2. Search for an industrial partner for the production and distribution of the nutraceutical / pharmaceutical product (suspension of bioadhesive liposomes containing the molecule or molecules of industrial interest). In doing this, the support of expert consultants in the defense of intellectual property will obviously be necessary to carry out those specific activities of technology transfer such as the preparation of secrecy and patent licensing agreements. The implementation of this strategy will bring the idea behind the patent to the industrial production of bioadhesive liposome suspensions, designed for example for sublingual administrations, containing the molecule or molecules of interest, of great attraction for the national and international market.

Accomplished results

 

The following results were achieved:

  1. Realization of a prototype on a pre-pilot scale, capable of much higher productions than the laboratory set-up.
  2. Preparation of confidentiality and patent licensing agreements, in order to facilitate the search for an industrial partner for the production and distribution of the nutraceutical / pharmaceutical product.

 

Financial support: € 56,900.00