Absorbable bio-network for sustained release of dexamethasone and hyaluronic acid

Abstract

An absorbable bio-network for preventing fibrous adhesions following surgical or traumatic injury to the hand is disclosed. The bio-network comprises a polymer mixture of poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) in a ratio of 60-80 wt% PLGA to 20-40 wt% PCL, and includes an inner drug reservoir formed of PLGA microspheres having a diameter of 20-50 μm and loaded with dexamethasone base at 1-5 wt%. The network is produced by electrospinning to obtain a membrane of 100-200 μm thickness, followed by application of a surface coating of hyaluronic acid and chitosan crosslinked with genipin. The construct provides a controlled drug-release profile characterized by a low initial release during the first two weeks and an increasing release thereafter over a period of 6-8 weeks. The system reduces adhesion formation without impairing early wound healing, and encompasses variations in polymer ratios, microsphere preparation, and coating conditions.

Description

[0001] Description

[0002] Technical Field

[0003] The invention relates to biomedical materials used for the prevention of postoperative fibrous adhesions.

[0004] Specifically, it concerns an absorbable polymeric bionetwork incorporating a controlled-release system for dexamethasone for use after surgical or traumatic injuries of the hand.

[0005] Background Art

[0006] Fibrous adhesions frequently develop following surgical repair or traumatic injury of hand structures, particularly tendons and soft tissues. Existing antiadhesion barriers include biodegradable films, hydrogels, and polymer membranes; however, these solutions often suffer from one or more limitations, such as:

[0007] • insufficient residence time at the injury site,

[0008] • uncontrolled or overly rapid drug release,

[0009] • weak mechanical performance or low flexibility,

[0010] • lack of combined anti-adhesion and pharmacological activity.Current drug-delivery platforms involving microspheres or polymer membranes do not simultaneously provide a dual-phase release profile with both early-stage safety and late-stage efficacy, nor do they integrate a surface coating that additionally reduces adhesion formation.

[0011] Disclosure of the Invention

[0012] Technical Problem

[0013] The invention aims to provide an absorbable system capable of reducing fibrous adhesion formation without interfering with the early healing phase, while ensuring sustained and temporally controlled delivery of dexamethasone.

[0014] Solution to the Problem

[0015] The invention provides an absorbable bio-network comprising:

[0016] • a polymer matrix formed from PLGA and PCL within a ratio range of 60-80 wt% PLGA to 20-40 wt% PCL, • an internal drug reservoir in the form of PLGA microspheres of 20-50 pm diameter containing dexamethasone base at 1-5 wt%,

[0017] • a surface layer composed of hyaluronic acid and chitosan crosslinked using genipin at 0.02-0.1%,• a membrane structure produced by electrospinning with a thickness of 100-200 pm,

[0018] • a drug-release profile characterized by a low initial release during the first 1-2 weeks followed by increased release for a total duration of 6-8 weeks.

[0019] Mode of Operation

[0020] The microsphere reservoir slows initial release, while the polymer matrix and surface coating modulate later release and provide mechanical and anti-adhesion benefits. The construct gradually degrades in vivo, thereby minimizing the need for removal.

[0021] Advantages of the Invention

[0022] The invention provides several technical advantages over the prior art:

[0023] 1. Defined and tunable degradation rate by adjusting PLGA / PCL ratios.

[0024] 2. Dual-phase drug-release profile optimized for healing physiology (low early —> high later).

[0025] 3. Targeted prevention of fibrous adhesions through combined mechanical and biochemical mechanisms.

[0026] 4. Enhanced flexibility and structural integrity compared with single-polymer membranes.5. Improved biocompatibility and anti-adhesion performance due to HA + chitosan + genipin surface chemistry.

[0027] 6. Manufacturing versatility, allowing modifications within defined ranges without altering the inventive concept.

Claims

Claimsain Claimn absorbable bio-network containing a therapeutic agent, haracterized by:1 . A polymer mixture of PLGA and PCL in a ratio ranging between 60-80% PLGA and 20-40% PCL by weight.

2. An active ingredient: Dexamethasone base at 1-5% by weight.

3. A drug reservoir comprising PLGA Microspheres with a diameter of 20-50 pm.

4. A surface layer composed of HA + Chitosan, crosslinked with Genipin (0.02-0.1%).

5. A drug-release mechanism with a Low — High pattern over 6-8 weeks.Dependent ClaimsClaim 2: The PLGA / PCL ratio is 70:30 by weight.Claim 3: The PLGA / PCL ratio is 50:50 by weight for slower egradation and higher flexibility.laim 4: The drug-loaded microspheres are prepared using a ouble-emulsion method.laim 5 : The membrane is prepared by electrospinning with a hickness of 100-200 pm.laim 6: The surface layer is applied by immersion and rosslinking for 12-24 hours.laim 7: Sterilization is performed using EtO, and storage is aintained at 2-8 °C.hird: Elements of Protection1. The PLGA / PCL ratio range: 60-80% : 20-40%.

2. The preferred ratio 70:30, with 50:50 included as an alternative within the protection scope.

3. Active ingredient: Dexamethasone 1-5%.

4. PLGA microspheres with a diameter of 20-50 pm.

5. Surface layer: HA + Chitosan + Genipin.

6. Drug-release curve: Low — High over 6-8 weeks.

7. Manufacturing method: double emulsion + electrospinning + crosslinking.

8. Protection covers any modifications within these ranges without departing from the core inventive concept.