CPP-Melphalan Conjugates for Non-Invasive Retinoblastoma Delivery
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Solution Overview
Problem
Current treatments for retinoblastoma, such as ophthalmectomy and extraocular radiotherapy, are invasive and inconvenient, especially for children, while intraocular injections require general anesthesia and have low bioavailability due to absorption barriers in the anterior ocular segment, necessitating a more effective and convenient mode of administration.
Innovation Solution
Development of covalent conjugates of cell-penetrating peptide derivatives with melphalan, which significantly enhance solubility and enable non-invasive intraocular delivery through eye drops, improving bioavailability and efficacy in treating posterior ocular segment diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intraocular injection is used to deliver melphalan, then the drug can reach the posterior ocular segment, but the procedure requires general anesthesia and has low bioavailability due to absorption barriers
Solution Approach 1:
The patent uses cell-penetrating peptide derivatives as intermediaries to facilitate drug delivery. The CPPs mediate the entry of melphalan into ocular cells, enabling effective delivery to the posterior segment without requiring injection. The peptide acts as a carrier that overcomes the absorption barriers mentioned in the contradiction.
Solution Approach 2:
The patent modifies the physical and chemical parameters of melphalan by conjugating it with cell-penetrating peptide derivatives. This changes the drug's properties to enable topical penetration through the corneal epithelium and achieve effective concentrations in the posterior ocular segment, resolving the bioavailability issue without injection.
2Ease of operation
If traditional eye drops are used, then the administration is convenient and non-invasive, but the bioavailability is no more than 5% due to absorption barriers in the anterior ocular segment
Solution Approach 1:
The patent creates a composite structure by covalently linking melphalan with cell-penetrating peptide derivatives. This composite material combines the therapeutic properties of melphalan with the cell-penetration capabilities of CPPs, enabling effective drug delivery through topical administration while overcoming the absorption barriers that limit traditional eye drops.
3Reliability
If ophthalmectomy or extraocular radiotherapy is performed, then the treatment is clinically mature and effective, but the procedures are invasive and inconvenient especially for children
Solution Approach 1:
The patent replaces the mechanical/invasive approaches of surgery and radiotherapy with a chemical/biological solution. By using cell-penetrating peptide-conjugated melphalan administered as eye drops, the treatment achieves therapeutic efficacy through biochemical mechanisms rather than physical intervention, eliminating the need for invasive procedures.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The conjugates achieve comparable in vivo efficacy to conventional intravitreal injections, reducing brain metastasis and improving drug absorption in the posterior ocular segment, with enhanced safety and convenience.
Implementation Method 1
Cell-penetrating peptides (CPPs) are short peptides with positive charges under physiological pH conditions, and can mediate the entry of the covalently or non-covalently linked molecules or drug delivery systems (e.g., liposomes, nanoparticles, micelles, etc.) into the cells
Data Source
AI summary
The present invention relates to a conjugate of cell-penetrating peptide and melphalan and a formulation comprising the same. Specifically, the present invention relates to a conjugate formed by covalently linking cell-penetrating peptide derivative to melphalan, a formulation comprising the conjugate, a method for treating diseases with the conjugate, and the application of the formulation in treating diseases.