Scope and Objectives

To develop a point of care, self-administrable haemostatic wound healing device for in field treatment of military personnel and first aid kit for civilian road accident. In addition to the paint in situ gel, the material will also be developed in the form of lyophilised hemostatic sponge/pellets, powder and flakes for deep wounds. The proposal aims at finetuning the prototypes and validating them in vitro and in vivo. Objectives: 1. To develop a point of care, self-administrable haemostatic wound healing in situ hydrogel for in field treatment of military personnel and first aid kit for civilian road accident. 2. To develop pellets and powder forms for deep injuries 3. To validate prototypes in vitro in comparison with standards 4. To perform acute toxicity of developed formulations. 5. Regulatory approvals for pilot clinical trial

Deliverables

In situ gelling self administrable, non-bulky, rapid acting haemostatic and antibacterial wound dressing for in field treatment of soldiers will be ready for transfer at the end of the project. 1. Five prototypes viz gel, powder, pellet, flakes, fabric have been developed for improved hemostatic activity. 2. Pellet and gel are designed for superficial and deep wound injuries. 3. Pellet/flakes have shown instant clotting and are designed for superficial injuries 4. Smart fabric has shown promising hemostatic activity and will be useful as a hemostatic bandage. 5. All prototypes have been validated for hemostatic activity and are superior to marketed formulation.

Videos

Scientific Output

Different formulations of nanocomposites like Gel, powder, Flakes and pellet were prepared and characterized by using scanning electron microscopy, x-ray diffraction analysis and fourier transform infrared spectroscopy. The nanocomposite gel shown a mesh like structure in SEM image. XRD spectroscopy revealed its amorphous nature, and it was confirmed that the nature is retained after processing and lyophilization. This confirms the compatibility of process. FTIR spectroscopy have shown characteristic peak of nanocomposite in all formulations. In vitro hemostatic activity of all formulations was studied first on goat blood and compared with marketed formulation celox. The developed formulations shown less clotting time i. e. 3 min than celox which was found to be more than 20 min. Further in vitro hemostatic activity was confirmed at SRL diagnostics. In vitro Biocompatibility study of all the formulations, viz. gel, powder, flakes and sponges has been performed on L929 mouse fibroblast cell lines. More than 90 percent cell viability confirms the biocompatible nature of all formulations. Stability studies of developed hemostatic powder formulation, gel and pellet was performed using ICH guidelines at 40 degC 75 percent RH, 25 degC 60 percent RH and 2-8 degC. Powder formulation was found to be stable for 6 months at accelerated conditions. In vivo hemostatic activity of developed prototype have been performed on 6 to 8 weeks old Spargue Dawley rats using tail amputation method, it has confirmed better hemostatic than marketed formulation. In vivo wound healing activity have been performed on 6 to 8 weeks old Spargue Dawley rats and results are satisfactory. Bandage and powder formulations have shown better wound healing activity when compared with gel. Acute dermal toxicity was performed in GLP approved lab using OECD guidelines at Bioneeds, Banglore. Results of acute dermal toxicity have shown that gel and pellets are safe to use till 2000 mg per kg of dose. It has been categorized as safe compound.

Results and outcome till date

1. Developed prototypes gel, powder, pellet and bandage have shown promising hemostatic activity.
2. Prototypes have been validated in vivo study, it was found that flakes, bandage, powder and gel are more efficient than marketed product.
3. Stability studies of developed hemostatic powder formulation, gel and pellet was performed using ICH guidelines at 40 degC 75 percent RH, 25 degC 60 percent RH and 2-8 degC. Powder formulation was found to be stable for 6 months at accelerated conditions.
4. In vivo hemostatic activity of developed prototype have been performed on 6 to 8 weeks old Spargue Dawley rats using liver incision method, it has confirmed better hemostatic than marketed formulation.
5. In vivo wound healing activity have been performed on 6 to 8 weeks old Spargue Dawley rats and results are satisfactory. Bandage and powder formulations have shown better wound healing activity when compared with gel.
6. Acute dermal toxicity was performed in GLP approved lab using OECD guidelines at Bioneeds, Banglore. Results of acute dermal toxicity have shown that gel and pellets are safe to use till 2000 mg per kg of dose. It has been categorized as safe compound.
7. Cell compatibility studies revealed biocompatible nature of developed formulations.
8 hemocompatibility studies demonstrated compatibility of formulation with blood components.
9. Skin sensitization studies shown safety of formulation and concluded that developed formulations are non sensitizer.
10. Intracutaneous studies confirmed non irritable nature and formulation and can be safely used on skin and mucosa.
11. Estimation of inflammatory markers in serum samples was performed using ELISA kits it can be concluded that developed formulations have exhibited anti- inflammatory activity.
12. Hemostatic activity was confirmed using liver incision model and it was found that gel and pellet can be used for deep wounds and are biocompatible and biodegradable in nature.

Societal benefit and impact anticipated

Uncontrollable hemorrhage is the leading cause of avoidable deaths in battle field and becomes more challenging in a remote battle field where the immediate medical care is difficult to achieve. There is an urgent need to stabilise the soldier temporarily at the field, to prevent life threatening blood loss, infections and pain and accelerate wound healing which can enable the soldier to complete first aid task prior to being transferred for hospital. Self-administrable haemostatic wound healing in situ hydrogel for in field treatment of military personnel will be effective tool to prevent such incidences. Similarly, In case of civilian road accidents lead to death because of unavailability immediate medication. Hence first aid kit for civilian road accident will be useful to circumvent such problem. Hence in present study, hemostatic gel, powder, pellets and bandage are prepared for effective hemostatic activity. Pellet and gel can also be used in deep wounds.

Next steps

Developed prototypes will be validated for biocompatibility as per ISO 1099310 medical devices guidelines. Skin sensitization study will be performed in GLP approved laboratory. All documentation like dossier reparation for preclinical evaluation and toxicology testing will be done for regulatory approvals.

Publications and reports

Nil

Patents

Nanocomposite haemostatic gel, flakes, powder, smart fabric and pellets (Ongoing).

Scholars and Project Staff

Post Doc 1 PhD 1 MTech and MSc: 4

Challenges faced

No major obstacles

Other information

Five prototypes developed and validated. Displayed in Army Technology Exhibition and well received.