Paclitaxel Poly(amino acid) Block Copolymer Formulation
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Solution Overview
Problem
Current paclitaxel formulations, such as those using Cremophor EL and albumin, face challenges including infusion-related side effects, stability issues, and the need for reconstitution, while synthetic polymers like PEG can accumulate in tissues and raise toxicity concerns.
Innovation Solution
A composition comprising paclitaxel and a poly(amino acid) block copolymer, specifically a copolymer of Formula I, which is suitable for administration without reconstitution in a common parenteral diluent, maintaining stability and potency, and potentially reducing side effects by avoiding the use of Cremophor EL and human-derived albumin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Cremophor EL is used as a formulation excipient, then paclitaxel solubility is improved, but infusion-related side effects increase
Solution Approach 1:
The patent extracts and removes Cremophor EL from the formulation system, replacing it with a poly(amino acid) block copolymer. This extraction eliminates the harmful side effects associated with Cremophor EL while maintaining the necessary solubility enhancement function through the alternative polymer excipient.
Solution Approach 2:
The patent changes the chemical parameter of the excipient from Cremophor EL (polyoxyethylated castor oil) to a poly(amino acid) block copolymer with specific composition (Formula I). This parameter change maintains solubility enhancement capabilities while eliminating the toxicological profile associated with Cremophor EL, including bronchospasm, hypotension, and anaphylactic reactions.
2Reliability
If albumin is used as a formulation excipient, then paclitaxel delivery is improved, but risk of viral transmission increases
Solution Approach 1:
The patent extracts and removes human-derived albumin from the formulation system, replacing it with a synthetic poly(amino acid) block copolymer. This extraction eliminates the theoretical risk of viral transmission or Creutzfeldt-Jakob disease while maintaining effective paclitaxel delivery capabilities.
Solution Approach 2:
The patent replaces a biologically derived, potentially hazardous material (albumin) with a synthetically produced, controlled polymer excipient. The synthetic polymer provides comparable delivery functionality without the biological contamination risks, effectively substituting a risky natural product with a safer synthetic alternative.
3Quantity of substance
If PEG-based polymers are used as excipients, then paclitaxel solubility is improved, but tissue accumulation and toxicity increase
Solution Approach 1:
The patent extracts and removes PEG-based polymers from the formulation system, replacing them with poly(amino acid) block copolymers. This extraction eliminates the concerns regarding anti-PEG antibodies and kidney-targeting toxicities while maintaining the solubility enhancement function necessary for paclitaxel delivery.
Solution Approach 2:
The patent employs a composite polymer structure (poly(amino acid) block copolymer) that combines hydrophobic and hydrophilic blocks to achieve solubility enhancement without the toxicological issues of PEG. The specific block structure (Formula I) provides both solubility improvement and biocompatibility, avoiding tissue accumulation and antibody formation.
4Object-affected harmful factors
If Abraxane is used as a formulation, then Cremophor EL side effects are eliminated, but preparation complexity increases
Solution Approach 1:
The patent extracts and removes the need for reconstitution steps by formulating paclitaxel with poly(amino acid) block copolymer in a manner that allows direct administration in common parenteral diluents. This eliminates the preparation complexity and foaming/clumping issues associated with Abraxane while maintaining elimination of Cremophor EL side effects.
Solution Approach 2:
The patent changes the formulation parameters to enable direct administration without reconstitution. The poly(amino acid) block copolymer formulation allows the drug to be administered directly in common parenteral diluents, simplifying the preparation process compared to Abraxane which requires careful reconstitution to avoid foaming and clumping.
Data Source
AI summary
This disclosure relates to the field of formulations of paclitaxel with a poly(amino acid) copolymer and methods of making and using thereof. Compositions herein are drug products suitable for the treatment of cancers.