Sequential release systems must overcome significant diffusion barriers to maintain therapeutic levels of multiple growth factors. In controlled trials, initial burst releases can reach 60-70% of loaded cargo within the first 24 hours, followed by sub-therapeutic delivery rates thereafter. The co-delivery challenge becomes particularly pronounced when multiple bioactives have distinct physicochemical properties and stability requirements—requiring carrier systems that can maintain distinct release profiles within a single formulation.

The fundamental challenge lies in engineering delivery systems that can release multiple bioactive agents with independent kinetics while preserving their structural integrity and biological activity.

This page brings together solutions from recent research—including dual-modifier excipient systems for sustained polyamine delivery, liposome-encapsulated peptide-exosome complexes from adipose-derived stem cells, controlled-release CNP agonist formulations, and silk protein stabilization techniques for growth factor preservation. These and other approaches demonstrate how sequential delivery challenges can be addressed to maximize therapeutic efficacy while minimizing off-target effects.

1. Composition with CD44 Receptor Ligand and Hyaluronic Acid Conjugate Delivered by Electromagnetic Techniques

AMPLIFICA HOLDINGS GROUP INC, 2025

Composition and methods for stimulating hair growth through the activation of CD44 receptors. The composition includes a naturally occurring ligand for CD44, such as osteopontin, and a hyaluronic acid conjugate. The composition is delivered via iontophoresis, electroporation, or radiofrequency thermal ablation to enhance its penetration through the skin barrier. The osteopontin-ligand conjugate modulates CD44 activation, leading to increased expression of hair growth-promoting genes and enhanced hair follicle regeneration.

2. Method for Preparing Liposome-Encapsulated Peptide-Exosome Complex from Adipose-Derived Stem Cells

BEIJING BOSHIYUAN HAIR RESEARCH CENTER, 2024

A method for preparing a targeted hair growth agent that combines active peptides with stem cell-derived exosomes. The agent is prepared through a multi-step process involving stem cell exosome extraction, peptide extraction, liposome encapsulation of the peptide-exosome complex, and final formulation of the agent. The exosomes are derived from adipose tissue and contain stem cells that release growth factors and other signaling molecules. The active peptides are isolated from these exosomes and encapsulated within liposomes, which are then formulated into a hair growth agent. This agent delivers the active peptides directly to hair follicles, promoting hair growth through targeted delivery of growth factors and other signaling molecules.

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3. Composition with Palmitoylethanolamide and Sucroester for Controlled Polyamine Release

GIULIANI SPA, 2024

Composition for controlled release of biologically active polyamines, particularly spermidine, to achieve prolonged therapeutic effects through sustained delivery. The composition combines palmitoylethanolamide with sucroester as excipients to modulate polyamine release, particularly in the colon region. This dual-modifier approach enables controlled release of spermidine from a carrier system, while maintaining therapeutic efficacy.

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4. TRPML Channel Agonists with Dual-Action Mechanism on Autophagy and TGFB1 Regulation

HANGZHOU NO.3 PEOPLES HOSPITAL, 2024

TRPML channel agonists promote hair growth by activating autophagy and regulating hair follicle regeneration. The agonists, particularly TRPML1 and TRPML3, enhance autophagy in dermal papilla cells while downregulating hair growth inhibitory factor TGFB1. This dual-action mechanism enables hair follicle miniaturization, hair cycle transition, and regeneration, offering a novel therapeutic approach for androgenic alopecia.

5. Controlled-Release Formulation of CNP Agonist and Growth Pathway Modulating Agent

ASCENDIS PHARMA GROWTH DISORDERS AS, 2023

Combination therapy for growth disorders using a controlled-release combination of a CNP agonist and a biologically active drug. The therapy combines a naturally occurring CNP agonist with a biologically active drug that targets specific growth-related pathways, providing enhanced efficacy and safety compared to monotherapy. The CNP agonist stimulates bone growth, while the biologically active drug targets specific growth factors or pathways involved in growth regulation. The combination enables targeted growth stimulation while minimizing potential side effects.

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6. Topical Epristeride Formulation with Transdermal Absorption Enhancer and Stabilizing Agents

JIANGSU LIANHUAN PHARMACEUTICAL CO LTD, 2023

A topical preparation of Epristeride for preventing and treating androgenic alopecia. The preparation combines Epristeride with a transdermal absorption enhancer, thickener, and stabilizer to deliver the active ingredient directly to the hair follicles. The formulation achieves a concentration of 0.1-10% Epristeride in a preparation that can be applied once daily, offering a localized treatment approach for hair loss.

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7. Topical Formulation with 5α-Reductase Inhibitor and Enhanced Follicular Delivery System

JIANGSU LIANHUAN PHARMACEUTICAL CO LTD, 2022

A topical formulation for preventing and treating androgenetic alopecia through targeted delivery of a specific 5α-reductase inhibitor. The formulation combines a potent 5α-reductase inhibitor with a delivery system that enhances its penetration through the hair follicle. The formulation is specifically designed to target the hair follicles where dihydrotestosterone (DHT) is produced, thereby preventing the conversion of testosterone to DHT and the subsequent hair loss associated with androgenetic alopecia. The formulation is formulated with a combination of cosolvents, transdermal absorption enhancers, thickening agents, and stabilizers to ensure effective penetration and stability through the skin.

CN114931546A-patent-drawing

8. Composition Comprising Growth Factors and Silk Protein for Enhanced Hair Follicle Stimulation

MEDICOSBIOTECH INC, 2022

A composition for promoting hair growth or suppressing hair loss that utilizes growth factors like VEGF, FGFα, FGFβ, TGF-β, IGF, KGF, and SCF to stimulate hair follicle activity. The composition contains a combination of these growth factors, along with silk protein, which is derived from natural silk fibers. The silk protein enhances the delivery and bioactivity of the growth factors, particularly in their roles in hair follicle development and capillary formation. This composition provides a sustained hair growth effect without the side effects associated with traditional treatments like minoxidil or finasteride.

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9. Controlled-Release CNP Agonist and Growth Hormone Analog Combination for Growth Disorders

ASCENDIS PHARMA GROWTH DISORDERS AS, 2022

Combination therapy for growth disorders using a controlled-release CNP agonist and a growth hormone (GH) analog. The therapy combines a biologically active CNP agonist with GH, which is administered in controlled-release form, to enhance growth-promoting effects. The combination provides a more effective treatment compared to GH alone, particularly in patients who do not respond to CNP agonists alone. The therapy can be administered in a single treatment session, with the controlled-release formulation providing sustained release of the growth hormone component.

10. Microcapsule Preparation Method Utilizing Exosome Encapsulation in Sodium Alginate Matrix

NANJING TIANLONGITUDINAL EIKANG BIOTECHNOLOGY CO LTD, 2022

A method to prepare microcapsules for hair growth using exosomes that avoids the need for subcutaneous injection. The method involves encapsulating exosome growth factors in a microcapsule matrix made from sodium alginate, emulsifiers, and vegetable oil. The exosomes are mixed with the other components and then dropped into a solution of sodium alginate at a specific concentration. The resulting microcapsules can be applied topically for hair growth promotion without the pain of injections.

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11. Pharmaceutical Composition Comprising Minoxidil and Traditional Chinese Medicine Extracts with Specific Molar Ratios

SHANGHAI UNIVERSITY OF TRADITIONAL CHINESE MEDICINE, 2021

Pharmaceutical composition for preventing and treating hair loss that combines minoxidil, a common hair growth drug, with traditional Chinese medicine extracts. The composition contains minoxidil and traditional Chinese medicine compounds like cedarol and baicalin in a molar ratio of 1:1 to 3:3. This combination improves hair growth effectiveness while reducing skin irritation compared to minoxidil alone. The composition can be used in medicines, health products, and foods for hair regeneration and growth.

CN113712968A-patent-drawing

12. Topical Formulation with Stage-Specific Growth Factors and Oligopeptides for Hair Follicle Development

SKINQRI LLC, 2020

A topical treatment for promoting hair growth that addresses the complex stages of hair follicle development. The treatment combines a synergistic blend of growth factors and oligopeptides specifically selected for each stage of hair growth, including anagen, catagen, telogen, and anagen phases. The formulation enables targeted delivery of these growth factors through mechanical and energetic means, including mechanical wounding and energy delivery, to enhance hair growth.

13. Covalently Linked Hair Loss Drug and Protein Transduction Domain with Cleavable Linker

GOOD T CELLS INC, 2020

Composition for preventing or treating hair loss that contains a drug for preventing or treating hair loss, like finasteride, covalently linked to a protein transduction domain (PTD) via a linker. The linked compound is delivered into cells, like dermal papilla cells, to effectively treat hair loss. The PTD aids cellular uptake and the linker prevents structural changes to the drug. A cleavage site can be included between the PTD and drug to activate the drug inside the cells.

14. Composition with Synergistic Compounds Targeting Hair Follicle Development Stages

LG Household & Health Care Ltd., LG HOUSEHOLD & HEALTH CARE LTD, 2020

Composition for preventing hair loss or promoting hair growth that addresses the underlying causes of hair follicle degeneration. The composition contains a synergistic blend of compounds that target multiple stages of hair follicle development, including cell proliferation, differentiation, and apoptosis. The active ingredients, including VEGF, IGF-1, and growth factors, promote hair growth while inhibiting the degenerative phase, while the combination of anti-hormonal and anti-inflammatory agents addresses the hormonal and stress-related factors contributing to hair loss. The composition is formulated as a hair growth tonic and is safe for use on the scalp without causing significant side effects.

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15. Composition Containing BMP Signaling Pathway Inhibitory Peptide from Neural Stem Cell Extract

Future City, MIRAE CT CO LTD, 2020

Hair growth promoting or preventing composition comprising a BMP signaling pathway inhibitory peptide derived from neural stem cell extract. The peptide, derived from TGFβ2 released from dermal papilla cells, selectively inhibits the BMP signaling pathway that normally delays hair growth, promoting differentiation of hair follicle stem cells to induce anagen phase. This composition can be used for hair growth promotion or prevention through the inhibition of hair loss mechanisms.

16. Gel Cream Composition with Acrylate Copolymer and Modified Multi-Effect Factor Solution for Hair Follicle Regeneration

BEIJING RM BIO-TECH CO LTD, 2019

Hair regenerating gel cream for treating alopecia areata and other hair loss conditions. The cream combines an acrylate copolymer, betaine, hyaluronic acid, sodium hydroxide, a modified multi-effect factor solution, and water to deliver a potent hair growth stimulus. The modified multi-effect factor solution enhances hair follicle regeneration by activating dermal papilla cells, promoting hair fiber production, and inhibiting inflammatory responses. The cream's composition creates a stable, multi-factor environment that supports stem cell activation and hair regeneration.

17. Composition Comprising Cholangio-3,5-Diene, Hair Growth Agents, Antiandrogens, Biologically Active Peptides, White Birch Extract, Dextran, Butylene Glycol, and Water

SHANGHAI LONGXI INVESTMENT CO LTD, 2019

Hair loss prevention and hair growth composition containing cholangio-3,5-diene, hair growth agents, antiandrogens, biologically active peptides, white birch extract, dextran, butylene glycol, and water. The composition improves hair growth, reduces hair loss, and enhances scalp health. The active ingredients work synergistically to promote hair follicle growth, repair, and anchoring, moisturize the scalp, and inhibit hair loss factors like DHT. The composition can be applied to hair products like oil, conditioner, lotion, shampoo, mask, etc.

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18. Pharmaceutical Composition with CXCL1 Protein and Minoxidil for Hair Follicle Stimulation

SCM LIFESCIENCE CO LTD, 2019

A pharmaceutical composition for preventing or treating hair loss comprising CXCL1 protein and minoxidil as an active ingredient, and a cosmetic composition for promoting hair growth comprising CXCL1 protein and minoxidil as an active ingredient. The composition combines CXCL1 protein with minoxidil to enhance hair growth by promoting blood flow in hair follicles.

19. Topical Compositions with Bimatoprost and Penetration Enhancers for Enhanced Dermal Absorption

ALLERGAN INC, 2018

Topical compositions for stimulating hair growth and treating hair loss that include bimatoprost, a compound approved for treating glaucoma, in combination with penetration enhancers. The penetration enhancers are used to improve absorption of the bimatoprost through the skin. The compositions are applied topically to promote hair growth and convert miniaturized hair into terminal hair. The penetration enhancers help deliver the bimatoprost deeper into the skin where it can more effectively stimulate hair growth.

20. Covalently Linked Finasteride-Peptide Compound with Enhanced Skin Penetration and Dual Mechanism for Hair Follicle Stimulation

CAREGEN CO LTD, 2017

A compound that enables hair growth through a novel mechanism of action. The compound combines finasteride and a peptide in a covalently linked structure, where the peptide enhances hair follicle growth while finasteride specifically targets the 5α-reductase enzyme responsible for hair loss. This synergistic approach enables both hair thinning prevention and regrowth, with the peptide peptide exhibiting enhanced keratinocyte proliferation and WNT signaling activation. The compound demonstrates superior skin penetration compared to conventional finasteride formulations, making it a more effective treatment for hair loss.

21. Conditioned Medium with Wnt7a-Overexpressing Mesenchymal Stem Cells for Hair Follicle Activation

22. Multiphasic Growth Factor Delivery System with Sequential Release from Carrier and Delivery Vehicle

23. Hair Care Composition with Stabilized Fibroblast Growth Factor Variant and Noggin Peptide

24. Hair Follicle Targeted Composition with Sirt2 Protein and Transduction Domain Fusion for Modulating Cell Proliferation

25. Synergistic Formulation of Bimatoprost and Minoxidil for Hair Growth Stimulation

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