WO2019224709A1 - Antibiotic delivery system - Google Patents
Antibiotic delivery system Download PDFInfo
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- WO2019224709A1 WO2019224709A1 PCT/IB2019/054179 IB2019054179W WO2019224709A1 WO 2019224709 A1 WO2019224709 A1 WO 2019224709A1 IB 2019054179 W IB2019054179 W IB 2019054179W WO 2019224709 A1 WO2019224709 A1 WO 2019224709A1
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- delivery system
- platelets
- antibiotics
- antibiotic
- loaded
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/04—Nitro compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/19—Platelets; Megacaryocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
Definitions
- the present invention relates to the development of a novel antibiotic (Ab) delivery system for combating microbial infection.
- platelet the smallest blood component
- the antibiotic loaded platelets are capable of killing microbes at very low Ab concentration.
- This invention can also be used to inhibit the growth and kill antibiotic resistance pathogenic strains.
- the Ab loading in the platelets makes the Abs invisible to the microorganisms and does not generate any immunogenicity and further resistance.
- liposomal system has some major drawbacks. Liposome mostly carries hydrophilic drugs rather than hydrophobic drugs. Release of hydrophobic drug from liposome faces some difficulties ( Foldvari el ah, (1993) Drug development and industrial pharmacy, 19(19), pp.2499-2517; and Nounou et ah, (2006) Acta Pharmaceutica, 56(3), pp.311-324). Moreover, elimination of liposome from blood is also a matter of concern (Torchilin (2005) Nature reviews Drug discovery, 4(2), p.l45).
- the metallic (or even polymeric) nanoparticle systems have limited biodegradability (Soppimath et ah, (2001) Journal of controlled release, 70(1-2), pp.l-20), toxicity and adverse immune-response (Le and Chen (2011) Small, 7(21), pp.2965-2980; and Ahamed et ah, (2010) Clinicazia acta, 411(23-24), rr.1841-1848).
- EP1191962 provides a device for allowing the injection of all of antimitotic, antibiotics or blood platelets when administered by slow intravenous.
- the disclosure of EP1191962 further points out the drawabacks of any residual products that are stagnant in the evacuation tubing are often thrown with it, resulting in under-treatment of the patient and risks to the environment.
- EP1191962 aims at providing specialized device for slow intravenous chemotherapy infusions (IVL): antimitotic for the treatment of cancers, but also antibiotic, anesthetic and valuable blood products such as blood platelets.
- IVL slow intravenous chemotherapy infusions
- US20180125893 provides a pure platelet-rich plasma (P-PRP) composition as an alternative to conventional antibiotic treatment of subclinical mastitis caused by Gram-positive bacteria in bovine including five live platelets and leukocytes, an anticoagulant, and an activating substance.
- P-PRP platelet-rich plasma
- platelets play a vital role in hemostasis, a process by which bleeding is stopped at the site of interrupted endothelium.
- hemostasis a process by which bleeding is stopped at the site of interrupted endothelium.
- circulating platelets attach with the exposed endothelium and get activated. After activation, they interact with each other and form platelet plug (primary hemostasis). This process in turn activate the coagulation cascade which results in fibrin deposition and formation of fibrin plug (secondary hemostasis) and thus prevent blood lose from vessel injuries.
- Microbial pathogenesis is one of the most critical health challenges occurring worldwide.
- Several ranges of antibiotics have been developed to control microbial pathogenesis. Due to increasing rate of antibiotic resistance development, newer antibiotic or newer technology for antibiotic delivery is required. As introduction of new antibiotic is very difficult, it is much more convenient to improve the existing delivery system rather than introducing new antibiotics.
- the present invention provides a portable device that allows the proper loading of the antibiotics inside the plate during the platelet transfusion.
- the present invention provides for the first time a delivery system wherein the platelets are laoded with antibiotics to improve the efficacy of the antibiotics, decrease the chances of developing resistance against the said antibiotics and does not have any biocompatibility issues with the recipient’s body.
- the present invention opens a new era and provides a safer approach towards antibiotic delivery.
- the present invention provides an antibiotic delivery system for combating microbial infection, comprising platelets loaded with antibiotics.
- the platelets are isolated from healthy human and/or animal donors.
- the present invention provides an antibiotic delivery system for combating microbial infection selected from infection caused by bacteria, viruses, protists, fungi or combination thereof.
- the antibiotic delivery system of the present invention is in form of tablets, capsules, creams, ointments, aerosols and/or patches.
- the platelets loaded with antibiotics comprises about 25 % of the loaded antibiotics.
- the antibiotics are selected from the group consisting water-soluble, water- insoluble (hydrophobic) antibiotics and/or combination thereof.
- the antibiotics are selected from the group consisting chloramphenicol, kanamycin, Oxytetracycline, Chlortetracycline, Tetracycline, Tiamulin, Gentocin, Lincomycin, Neomycin, Spectomycin, Sulfamethazine, Tylosin, Penicillin G Potassium, tetracycline hydrochloride, moxifloxacin hydrochloride, and ciprofloxacin hydrochloride and/or combination thereof.
- hydrophobic antibiotics are encapsulated in lipid or polymer prior to loading on platelets.
- the antibiotic delivery system of the present invention is for treating Bronchitis, Chest colds, Common Cold, Ear Infection, Influenza (Flu), Sinus Infection (Sinusitis), Sore Throat, Urinary Tract Infection, viral infections, chicken pox, or Measles.
- the antibiotic delivery system of the present invention is for combating microbial infection comprising mixing antibiotics with platelets in a platelets and drug mixing chamber.
- the present invention provides a method of administration of an antibiotic delivery system for combating microbial infection, comprising platelets loaded with antibiotics wherein the delivery system is in liquid, and/or gel form.
- the delivery system is in powdered and/or tablet form.
- the delivery system is administered either by oral route, intravenous route, rectal, topical, sublingual, subcutaneous, buccal, nasal, intravaginal, and/or intradermal route.
- the present invention provides a method of treating a recipient human and/or animal by administering the delivery system for combating microbial infection, comprising platelets loaded with antibiotics
- the present invention provides a device for mixing platelet and antibiotics to obtain platelets loaded with antibiotics comprising a component for providing platelets (1) to a magnetic bead stirrer (3); a component for providing antibiotics or encapsulated antibiotics in polymer or lipid (2) to a magnetic bead stirrer(3); and a magnetic bead stirrer (3) to receive antibiotics and platelets from components (1) and (2); wherein the device is controlled with a steeper motor and open source electronic platform based micro controller.
- the present invention provides novel antibiotic delivery system, wherein the platelets isolated form healthy human donors are loaded with Ab.
- the delivery system shows enhanced efficacy, does not have any biocompatibility issues and reduce chances of strains developing resistance to the Ab loaded in the platelets.
- the inventors have used the property of platelets, a blood component to engulf small molecules even bacteria and other microbes and obtained a novel delivery system.
- the inventors of the present invention have utilized this property and loaded antibiotics inside platelet.
- the antibiotic loaded platelet was found to be stable when studied through experimental processes. It has been previously reported that platlets generally engulf 25% to 30% of the small molecules in vitro. As a case study the nonpathogenic bacterial strain E. coli as a model microorganism has been used in the present invention.
- the bactericidal efficacy of the antibiotics loaded platelets was much higher, and the loaded platelets were able to kill the bacteria in such a low concentration at which the free antibiotic is barely effective.
- the present invention also provides a portable, low cost fluidics device where the antibiotics are loaded into the platelets in a controlled manner during platelet transfusion.
- FIG. 1 Aggregation profile of platelets in presence and absence of antibiotic with different agonists: The aggregation profile of the platelets in presence of ADP and collagen as agonists at different time interval (0, 2 and 4 hrs.). The percentage of aggregation of platelets in absence (Control ADP) and presence (Ab ADP) of chloramphenicol is provided (figure A). For collagen-induced aggregation the percentage of aggregation is provided in Figure B.
- Figure C provides the Arachidonic acid induced aggregation of platelets at 4 hours for control platelets and antibiotic loaded platelets respectively.
- Figure 2 Confocal microscopic images of E. coli and platelets.
- Figure 3 Z- section images of platelet and E. coli cells (stained with DAPI) after 1 hr. of incubation.
- Figure 4 E. coli cell viability with different types of treatment.
- Figure 5 Response of Kanamycin sensitive and resistant strain of E. coli towards kanamycin loaded platelet.
- Figure 6 Comparison of Bactericidal efficacy of the hydrophobic antibiotics loaded in platelets.
- Figure 7 Schematic representation of antibiotic delivery through platelets.
- the main aim is to investigate the role of platelets as antibiotic delivery system. It is reported that platelet can uptake soluble drugs and small particulate matter from the surroundings (Deb et ah, (2011) Nanomedicine: Nanotechnology, Biology and Medicine, 7(4), pp.376-384; and White (2005) Platelets, 16(2), pp.121-131).
- the inventors of the present invention have exploited this property of platelets to load antibiotic in it. This is not exactly phagocytosis as the engulfed material remains intact inside the cells. So, the internalized materials (here chloramphenicol) retain its activity even when remaining inside the platelets.
- the main objective of the study was to develop an invisible and highly biocompatible mode of delivery system that can effectively kill bacteria.
- the factors were: firstly, being a blood component, they are non-immunogenic. Secondly, a well-defined interaction of platelets with microorganisms may be expected. Thirdly, platelets can uptake a substantial amount of drug (25% to 30% of applied drug concentration) (Sarkar et al, (2013) Pharmaceutical research, 30(11), pp.2785-2794) and upon aggregation, they can release the same.
- Figure 4 provides that when platelets were loaded with Chloramphenicol (Ab) and treated with E.
- a small portable device has been designed that allows the proper loading of the antibiotics inside platelet.
- the experimental results provide that platelet can be used as antibiotic delivery vehicle.
- the proposed method can be used to combat the bacterial infection where direct interaction between platelet- bacteria takes place and can be further extended to treatment of viral infection as there is well documented interaction observed between platelet and virus (Youssefian et al., (2002) Blood, 99(11), pp.402l- 4029).
- Platelet isolation and antibiotic loading is done by collecting blood from healthy donors by venipuncture into plastic tubes containing a suitable buffer. The collected blood was then centrifuged at about 150 to 250 g and preferably at about 200 g for about 10 to 14 min and preferably for about 12 min to isolate platelet rich plasma (PRP). Platelet poor plasma (PPP) was obtained by centrifuging the blood at about 1000 rpm to 1400 rpm and preferably at about 1200 g for about 8 to 12 min and preferable for about 10 min. The PPP served as the blank for aggregometric study. All in vitro experiments were done within about 2 to 6 hours and preferably within about 4 hours of drawing the blood from the donors.
- PPP platelet rich plasma
- Antibiotic of choice was loaded into the platelets by means of diffusion method.
- Antibiotic final applied concentration of about 6.25 pg / ml
- PRP final applied concentration of about 6.25 pg / ml
- apyrase final concentration 0.2 U/mL
- the excess drug containing supernatant was discarded carefully and the pellet was dissolved in PBS.
- the antibiotic-loaded platelet was washed for another two to four times or preferably for two times following the same procedure. After final washing, the pellet was re-suspended in LB broth keeping platelet count of about 1,50, 000/ml.
- Adenosine di phosphate (ADP) final concentration 10 mM
- collagen final concentration 4 pg / ml
- arachidonic acid AA
- the aggregation experiment was run for about 2 to 6 minutes and preferably for about 4 minutes with a predetermined stirring rate of about 800 to 1200 rpm or preferably at about 1000 rpm at about 35 °C to 39 °C or preferably at about 37°C. This experiment was repeated for 2 to 4 times or preferably for 3 times.
- the delivery system of the present invention has high industrial importance as the same antibiotics show increased efficacy once loaded inside the platelet.
- Plasma samples Blood was collected from healthy donors by venipuncture into plastic tubes containing sodium citrate buffer. The collected blood was then centrifuged at about 200 g for about 12 min to isolate platelet rich plasma (PRP). Platelet poor plasma (PPP) was obtained by centrifuging the blood at about 1200 g for about 10 min. The PPP served as the blank for aggregometric study. All in vitro experiments were done within 4 hours of drawing the blood from the donors. Chloramphenicol antibiotic was loaded into the platelets by means of diffusion method. In short, Chloramphenicol (final applied concentration of about 6.25 pg / ml) was incubated with PRP at about 37 °C for about 1 hour.
- apyrase final concentration 0.2 U/mL was added and centrifuged at about 2000 rpm in a swing out centrifugation machine. The excess drug containing supernatant was discarded carefully and the pellet was dissolved in PBS. The antibiotic-loaded platelet was washed for another two times following the same procedure. After final washing, the pellet was re-suspended in LB broth keeping platelet count of about 1,50, 000/ml.
- the hydrophobic antibiotic was loaded into the Polymer nanoparticles by nano precipitation technique.
- the hydrophobic antibiotic was solubilized in a volatile organic solvent containing hydrophobic polymer (Poly-caprolactone).
- the aqueous phase for polymer nanoparticles synthesis was 1% Pluronic F127 (w/v).
- the particles size of the antibiotic loaded nanoparticles was found to be around 200 nm.
- the antibiotic loaded nanoparticles were incubated with PRP and were taken up by the platelets. Any other FDA approved polymers like PLGA can also be used for the same purpose.
- the hydrophobic antibiotics can be encapsulated inside lipid vesicles too where POPC, DPPC etc. can be used as antibiotic carrier.
- Platelet aggregation study was done to detect the effect of applied Chloramphenicol (Ab) on platelets.
- Adenosine di phosphate (ADP) final concentration 10 mM
- collagen final concentration 4 pg / ml
- arachidonic acid AA
- All the reagents were purchased from Chrono-log and Chrono-log aggregometer (model no 700) Chrono-log, Havertown, USA, was used for platelet functioning test.
- PRP was isolated by the same procedure as stated earlier in step 1.
- Chloramphenicol (Ab) (final concentration 6.25 pg/ ml) was added to the PRP and incubated at about 37°C. Another portion of PRP was kept as control. At different time interval (0, 2 and 4 hr) PRP was taken from both control and test; and functionality of platelet was measured by ADP, Collagen and AA. The aggregation experiment was run for about 4 minutes with a predetermined stirring rate of about 1000 rpm at about 37 °C. This experiment had been repeated for about 3 times.
- Figure 1 demonstrates the aggregation profile of platelets in presence and absence of antiobiotic with different agonists viz. Adenosine di phosphate (ADP), collagen and Arachidonic acid (AA).
- ADP Adenosine di phosphate
- AA Arachidonic acid
- Figure 1A and 1B The aggregation profile of the platelets in presence of ADP and collagen as agonists at different time interval (0, 2 and 4 hrs.) is shown in Figure 1A and 1B.
- the percentage of aggregation of platelets in absence (Control ADP) and presence (Ab ADP) of chloramphenicol (Ab) was about 74%, 71%, 70% and 72%, 73% 70% respectively at 0, 2 and 4 hr when ADP was used (Figure 1A).
- Figure 1C is the Arachidonic acid (AA) induced aggregation of platelets at about 4 hours where percentage of aggregation was about 74% and 75% for control platelets and antibiotic loaded platelets respectively.
- Gram -ve bacteria E. coli ATCC 25922 was used for the study.
- the bacterial cells were grown overnight in LB media until mid-logarithm phase was achieved.
- the optical density of the culture was measured and adjusted to about 10 6 CFU/ml.
- the bacterial culture was then exposed to various treatment groups including antibiotic solution, control platelets and platelets loaded with antibiotic and further incubated at about 37 °C.
- the aliquots were withdrawn immediately, and at time interval of about 30 minutes, 60 minutes and 120 minutes and placed on the agar plates. After overnight incubation, the colonies were counted manually and bactericidal activity was calculated (Shireen et ah, (2009) Peptides, 30(9), pp.1627-1635).
- Figure 5 and Table 1 clearly provide the comparative analysis of the response of Kanamycin (Ab) sensitive and resistant strain of E. coli towards kanamycin loaded platelet (Plt-Ab).
- the upper panel of the image represents plates of kanamycin sensitive strain of E. coli treated with free Kanamycin (Kan treated), Kanamycin loaded platelet (Platelet-Kan treated) and free platelet. Untreated cells of E. coli strain served as the control.
- Lower panel represents plates of the Kanamycin resistant strain of E. coli treated with free Kanamycin and platelet loaded with Kanamycin.
- Figure 5 explicitly provides the comparative analysis of efficacy between Kan loaded platelets, platelets and only Ab.
- Both the Ab-sensitive and Ab-resistant strains of E. coli showed highsusceptibility to platelets loaded with Ab (Plt-Ab), as compared to other controls. This makes it evident that the platelets loaded with Ab are also effective (in addition to Ab sensitive strains) against those strains which are or have grown resistance towards the known Ab.
- Figure 6 provides the bactericidal activity of the hydrophobic antibiotics which are insoluble in water and cannot be loaded to the platelets. Prior to loading they were encapsulated in FDA approved polymer or lipid vesicles. The polymer encapsulated/ lipid encapsulated antibiotic loaded platelet showed similar enhanced efficacy as it was found in case of hydrophilic antibiotic loaded platelet.
- the antibiotic control here shows the activity of the antibiotics when dissolved in organic solvents such as ethanol/ DMSO.
- E. coli was cultured as stated earlier. Platelet was prepared following the same procedure. After preparation of platelets, E. coli cells were stained by DAPI (concentrate 0.5 pg/ml) following PBS washing to remove excess stain and was mixed with platelet ( E . coli and platelet ratio is 1:2) and incubated in a bacterial incubator at about 37 °C with a stirring speed of about 200 rpm for about 1 hour. Next, the platelet- E. coli mixture was fixed with about 4% para- formaldehyde. Then in a grease-free glass slide, 10 pl of the suspension was taken and a cover slip was placed on the slide and edges were sealed. The slides were then seen under a laser confocal microscope of Olympus models no IX 81 FV 1,000 with 60x objective lenses.
- Figure 2 provides Confocal microscopic images of E. coli and platelets.
- Figure (2A-2C) demonstrates the bright field, fluorescent and corresponding over lapping images of E. coli cells respectively.
- Figures (2D-2F) represents the respective bright field, fluorescent and corresponding over lapping images of E. coli in presence of platelets after 1 hr. of incubation.
- Figures (2G-2I) shows bright field, fluorescent and corresponding over lapping images of E. coli in presence of platelets after 2 hr. of incubation.
- Figure (2J) is the bright field image of platelets.
- Figures (2A-2J) were captured at 60X magnification.
- Figures (2K-2L) represent the higher magnification (400X) images of platelet and bacterial cell interaction in bright field and its fluorescent overlapping mode respectively.
- Figure 3 provides Z- section images of platelet and E. coli cells (stained with DAPI) after 1 hr. of incubation.
- Drug mixed platelets can be delivered to the patients (4) in a simple manner by the device as depicted in Figure 7.
- the platelets (1) and Antibiotic or polymer/ lipid encapsulated antibiotic (2) were injected separately in a magnetic bead for stirring (3) in a Platelet antibiotic mixing device. Once the stirring was done the platelets loaded with antibiotics can be injected into patients (4).
- the platelets antibiotic mixing device and the magnetic bead stirrer (3) are further controlled with a steeper motor (not shown in Figure) and open source electronic platform (for example aurdino) based micro controller throughout the mixing.
- Figure 4 provides E. coli cell viability with different types of treatment.
- Figure (4A) represents the percentage of viability of E. coli cells when treated with free Chloramphenicol (Ab control), platelet (Plt control) and chloramphenicol loaded platelet (Plt-Ab) in a time dependent manner. E. coli cells without any treatment serves as the control.
- Figure (4B) demonstrates the bar diagram with error bar of the viability percentage of E. coli cells of individual treatment group at 0, 30, 60 and 120 min respectively. The results of Figure 4 clearly demonstrate the success of the delivery system of the present invention.
- the platelets loaded with Ab (Plt-Ab) showed a sharp decrease in the percent viability, leading to total annihilation of the target microorganism within about 2 hours of the treatment.
- Figure 4 clearly provides comparative analysis of the delivery system of the present invention with antibiotic and platelet controls used separately on same target microorganisms.
- the data of Table 1 further substantiates that not only the delivery system of the present invention is more effective than the individual components; the delivery system works synergistically to provide better results than the individual components.
- Table 1 The following Table depicts the % viability of the bacterial culture when exposed to various treatment groups (Ab control; Plt control; Plt-Ab) at different time intervals.
- the delivery system of present invention is effective against microorganisms, even when loaded with very small amount or concentrationn of Ab.
- the delivery system of present invention is also effective against microorganisms which are or have turned into resistant strains to the Ab loaded in the platelets.
- the delivery system of the present invention does not allow the microorganisms which are sensitive to the said Ab, to develop into a resistant strain.
- the delivery system of the present invention provides a fast and effective way of killing microorganisms.
- the delivery system of the present invention is a very simple and easy method without employing any expensive technology or equipment(s).
- the delivery system of the present invention does not pose any biocompatibility issues in the recipient’s body.
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Abstract
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2001058266A1 (en) * | 2000-02-10 | 2001-08-16 | The Regents Of The University Of California | Therapeutic platelets and methods |
WO2016205009A1 (en) * | 2015-06-19 | 2016-12-22 | The Regents Of The University Of California | Treating infection by a platelet-targeting microbe using nanoparticles |
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WO2001058266A1 (en) * | 2000-02-10 | 2001-08-16 | The Regents Of The University Of California | Therapeutic platelets and methods |
WO2016205009A1 (en) * | 2015-06-19 | 2016-12-22 | The Regents Of The University Of California | Treating infection by a platelet-targeting microbe using nanoparticles |
Non-Patent Citations (3)
Title |
---|
CHE-MING J. H ET AL.: "Nanoparticle biointerfacing via platelet membrane cloaking", NATURE, vol. 526, no. 7571, October 2015 (2015-10-01), pages 118 - 121, XP055323590, DOI: 10.1038/nature15373 * |
ORCUTT M: "Nanoparticles in Disguise Are a More Potent Antibiotic Treatment", MIT TECHNOLOGY REVIEW, September 2015 (2015-09-01) * |
SHI Q ET AL.: "Platelets as delivery systems for disease treatments", ADVANCED DRUG DELIVERY REVIEWS, vol. 62, no. 12, September 2010 (2010-09-01), pages 1196 - 1203, XP027509888, DOI: 10.1016/j.addr.2010.06.007 * |
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