Polymer Nanoencapsulation Platform (PNPs)
Polymer nanoparticles encapsulation drug provides the benefit of bioavailability, pharmacokinetic issues, and drug distribution, reduced toxicity of the drug. However, polymer nanoparticles encapsulation drug delivery still holds some challenges that low penetration and fragility of large molecules.
In recent years, chemical conjugation-based nanoencapsulation of bio-macromolecules has been extensively studied in academics, because such conventional nanoencapsulation technology was demonstrated to improve the stability of certain biomacromolecules and to enhance their therapeutic effects. However, commercial implementations of the conventional nanoecapsulation are rarely successful with an exception of PEG conjugation system. The conventional design of nanoencapsulation is intrinsically complex in chemistry, in process of surface modification, and in purification, rendering it difficult, sometimes impossible, to meet stringent regulatory requirements.
Conventional polymeric nanoencapsulated biopharmaceuticals require chemical conjugation between the polymers and the biopharmaceutical molecules. Biopharmaceuticals are in general sensitive to the variations in solution environments, such as salt concentration, ionic strength, solution pH, chemical compositions, temperature, and even radiation.
Polymeric conjugation requires harsh chemical reactions, in which the chemical reagents may destabilize or even denature the biopharmaceuticals, which the resulting polymers are supposed to protect. After conjugation reaction, the purification of polymer conjugated biopharmaceuticals often imposes even bigger challenges due to complex structures and altered surface properties of the resulting encapsulated products.
Considering the instability and difficult absorption of biopharmaceutical products in GI tract, biopharmaceuticals are often limited to certain topical administration routes such as intravenous injection/infusion, intramuscular injection, etc. Injectable formulations have to be sterile and the residual reagents of conjugation reaction are always under strict scrutinization by FDA.
The sterilization and residual reagent requirements in accordance with FDA regulations render the purification of traditional polymer conjugated biopharmaceuticals even more challenging. All these factors contribute to the hefty manufacturing cost of conventional polymeric nanoencapsulated biopharmaceuticals and sometimes their failures in IND reviews.
Lavoisier Polymer Nanoencapsulation Platform
Lavoisier’s proprietary polymer nanoencapsulation platform is aimed to address a variety of challenges in the commercialization of biopharmaceuticals, such as therapeutic enzymes, vaccines, and monoclonal antibodies. Endeavors and achievements of applying the Lavoisier platform include mitigating undesirable immune responses generated by a given therapeutic biopharmaceutical; enhancing therapeutic effect through controlled delivery of the biopharmaceutical in vivo; and/or stabilizing the biopharmaceutical from manufacturing to administration.
In recent years, chemical conjugation-based nanoencapsulation of bio-macromolecules has been extensively studied in academics, because such conventional nanoencapsulation technology was demonstrated to improve the stability of certain biomacromolecules and to enhance their therapeutic effects. However, commercial implementations of the conventional nanoecapsulation are rarely successful with an exception of PEG conjugation system. The conventional design of nanoencapsulation is intrinsically complex in chemistry, in process of surface modification, and in purification, rendering it difficult, sometimes impossible, to meet stringent regulatory requirements.
Lavoisier polymer platform is designed with a focus on a series of amphiphilic polyelectrolytes. Typical amphiphilic polyelectrolytes/polymers used in Lavoisier platform is represented by the following structure which may include a neutrally charged hydrophobic monomer moiety, a neutrally charged hydrophilic monomer moiety, an anionic monomer moiety, a cationic monomer moiety, and/or a zwitterionic monomer moiety . Such polymers are characterized by their ability to nanoencapsulate target biopharmaceuticals. The desired properties, such as mitigating undesirable immune responses of a biopharmaceutical; enhancing therapeutic effect of the biopharmaceutical in vivo; and/or stabilizing the biopharmaceutical from manufacturing to administration, can be achieved by carefully selecting the species of monomers in the polyelectrolytes, the corresponding ratios among the selected monomers, and branching and molecular weight of the polyelectrolytes. The desired properties may be achieved individually or simultaneously based on the circumstances of therapeutical applications.
Conventional polymeric nanoencapsulated biopharmaceuticals requires chemical conjugation between the polymers and the biopharmaceutical molecules. Biopharmaceuticals are in general sensitive to the variations in solution environments, such as salt concentration, ionic strength, solution pH, chemical compositions, temperature, and even radiation.
Polymeric conjugation requires harsh chemical reactions, in which the chemical reagents may destabilize or even denature the biopharmaceuticals, which the resulting polymers are supposed to protect. After conjugation reaction, the purification of polymer conjugated biopharmaceuticals often imposes even bigger challenges due to complex structures and altered surface properties of the resulting encapsulated products. Considering the instability and difficult absorption of biopharmaceutical products in GI tract, biopharmaceuticals are often limited to certain topical administration routes such as intravenous injection/infusion, intramuscular injection, etc. Injectable formulations have to be sterile and the residual reagents of conjugation reaction are always under strict scrutinization by FDA.
The sterilization and residual reagent requirements in accordance with FDA regulations render the purification of traditional polymer conjugated biopharmaceuticals even more challenging. All these factors contribute to the hefty manufacturing cost of conventional polymeric nanoencapsulated biopharmaceuticals and sometimes their failures in IND reviews.
Lavoisier Research and Design
Lavoisier has revisited the philosophy of polymer physics, biophysics, and polymer chemistry and creatively combined the knowledge in these scientific disciplines to address the barriers associated the conventional wisdom of designing nanoencapsulation. Lavoisier polymer platform, therefore, provides a revolutionary solution to the problems faced by conventional polymeric nanoencapsulated biopharmaceuticals.
Specifically, Lavoisier polymer platform is safe and easy to manufacture and does not require chemical conjugation between the polymers and the biopharmaceutical. Lavoisier polymer may automatically form nanoencapsulation layer around a specific biopharmaceutical molecule upon contact with the molecule. The nanoencapsulation with Lavoisier polymer platform requires mild conditions.
- Lavoisier encapsulation process is flexible, versatile, and easy to control. It fits every requirement in QbD (quality by design) and CMC requirements in IND.
- Formulations of Lavoisier nanoencapsulation may be more easily produced in processes that fully comply with Good Manufacturing Practice (GMP)
- Lavoisier’s nanoencapsulation platform may be applied to generate immune tolerant therapeutic enzymes, monoclonal antibodies, and viral vectors
- Proprietary polymer as excipient is suitable for production at a commercial scale via a well-controlled and scalable manufacturing process
Design Advantage of
Lavoisier Polymer Nanoencapsulation Platform
Eliminating the Chemical Reaction to Conjugate Polymers and Biopharmaceuticals
Lavoisier platform may be applied to encapsulate a wide variety of biopharmaceuticals; whereas conventional polymeric conjugation nanoencapsulation method is limited to a few chemically stable biopharmaceutical enzymes. Lavoisier polymer platform also enables greater flexibility to select the species of monomers to optimize the polymer’s ability to nanoencapsulate a target biopharmaceutical. In comparison, the selection of monomers is rather limited for the conventional polymeric conjugation nanoencapsulation due to the same chemical stability concerns of target biopharmaceuticals.
Reducing the Manufacturing Cost
Lavoisier polymer platform can be easily applied in the preparation of nanoencapsulated injectable formulations because the polymer and biopharmaceutical may be purified and sterilized separately before mixing and nanoencapsulation and there is no need to further purify or sterilize the final products. In this way, the procedure of preparing nanoencapsulated biopharmaceuticals using Lavoisier platform is greatly simplified and scalable in comparison to conventional polymeric nanoencapsulated biopharmaceuticals and therefore vastly reducing the manufacturing cost.
Compare Conventional Polymeric Nanoencapsulated Biopharmaceuticals
Chemical conjugation between the polymers and the biopharmaceutical molecules. Biopharmaceuticals are in general sensitive to the variations in solution environments, such as salt concentration, ionic strength, solution pH, chemical compositions, temperature, and even radiation. Polymeric conjugation requires harsh chemical reactions, in which the chemical reagents may destabilize or even denature the biopharmaceuticals, which the resulting polymers are supposed to protect.
Custom Specific Treatment Biopharmaceuticals
Applying Lavoisier encapsulation platform to a series of selected biotherapeutics for treating various diseases. Advancing Lavoisier platform in reducing/enhancing/fine-tuning immunogenicity of biopharmaceuticals of interest-based on the needs of specific treatments.