AU2021104207A4 - Halloysite nanotube as a modified drug release carrier for 6-mercaptopurine - Google Patents
Halloysite nanotube as a modified drug release carrier for 6-mercaptopurine Download PDFInfo
- Publication number
- AU2021104207A4 AU2021104207A4 AU2021104207A AU2021104207A AU2021104207A4 AU 2021104207 A4 AU2021104207 A4 AU 2021104207A4 AU 2021104207 A AU2021104207 A AU 2021104207A AU 2021104207 A AU2021104207 A AU 2021104207A AU 2021104207 A4 AU2021104207 A4 AU 2021104207A4
- Authority
- AU
- Australia
- Prior art keywords
- formulation
- drug
- drug release
- tumor growth
- mercaptopurine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 229940079593 drug Drugs 0.000 title claims abstract description 65
- 239000003814 drug Substances 0.000 title claims abstract description 65
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229960001428 mercaptopurine Drugs 0.000 title claims abstract description 19
- HPTYUNKZVDYXLP-UHFFFAOYSA-N aluminum;trihydroxy(trihydroxysilyloxy)silane;hydrate Chemical compound O.[Al].[Al].O[Si](O)(O)O[Si](O)(O)O HPTYUNKZVDYXLP-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 229910052621 halloysite Inorganic materials 0.000 title claims abstract description 13
- 239000002071 nanotube Substances 0.000 title claims abstract description 7
- 239000000203 mixture Substances 0.000 claims abstract description 58
- 238000009472 formulation Methods 0.000 claims abstract description 57
- 101000683591 Homo sapiens Ras-responsive element-binding protein 1 Proteins 0.000 claims abstract description 24
- 230000004614 tumor growth Effects 0.000 claims abstract description 17
- 230000005764 inhibitory process Effects 0.000 claims abstract description 14
- 238000000338 in vitro Methods 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 7
- 229920003141 Eudragit® S 100 Polymers 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 230000001186 cumulative effect Effects 0.000 claims description 4
- 238000012377 drug delivery Methods 0.000 claims description 4
- 238000011068 loading method Methods 0.000 claims description 4
- 230000003013 cytotoxicity Effects 0.000 claims description 3
- 231100000135 cytotoxicity Toxicity 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 101150004367 Il4i1 gene Proteins 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 230000001988 toxicity Effects 0.000 claims 1
- 231100000419 toxicity Toxicity 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 16
- 238000012384 transportation and delivery Methods 0.000 abstract description 5
- 239000008363 phosphate buffer Substances 0.000 abstract description 3
- 230000002459 sustained effect Effects 0.000 abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 3
- 210000004881 tumor cell Anatomy 0.000 abstract 2
- 238000002512 chemotherapy Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000012430 stability testing Methods 0.000 abstract 1
- 230000002476 tumorcidal effect Effects 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 description 13
- 239000002246 antineoplastic agent Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000013268 sustained release Methods 0.000 description 8
- 239000012730 sustained-release form Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 229940034982 antineoplastic agent Drugs 0.000 description 6
- 230000034994 death Effects 0.000 description 5
- 231100000517 death Toxicity 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 238000004626 scanning electron microscopy Methods 0.000 description 4
- 238000003828 vacuum filtration Methods 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 231100000057 systemic toxicity Toxicity 0.000 description 3
- 238000002525 ultrasonication Methods 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000013095 identification testing Methods 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 238000005496 tempering Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0092—Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nanotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Disclosed herein is a halloysite nanotube which is a modified drug release carrier for 6
mercaptopurine. We selected 6-Mercaptopurine as a model drug for this study, because its
insolubility in water makes it difficult to administer systemically by other means and because of
the potential applications of 6-Mercaptopurinein chemotherapy.All the formulation showed
sustained released of the drug when investigated of 20 hrs.in phosphate buffer pH 7.4.
Formulation Fl, F2, F3 and F4 showed percentage drug release which was about 89.56, 74.36,
75.13 and 75.74% respectively. Which showed that formulation with higher entrapment
efficiency possess maximum percentage drug release.Stability testing were performed by
randomly selected formulations were subjected to stability studies conditions at 5±30 C, room
temperature (25±20C with 60±5% RH) and 400 C with 75±5% relative humidity for a period of 3
months. From the stability studies it was confirmed that the formulations are stable at
temperature and humidity. In this study estimation of % tumor growth inhibition of formulation
was based on changes in tumor cell line. In the study the formulation was injected into the tumor
cell. In the case of the MCF-7 tumor 6-Mercaptopurine without HNTs appears to have less
tumoricidal effect. The drug show 12.34 % tumor growth inhibition and the formulation F1
showed2l.82% tumor growth inhibition, the formulation Fl has maximum% tumor growth
inhibition. Formulation F2, F3 and F4 showed 16.72, 19.11, 18.17 % tumor growth inhibition
respectively. The effectiveness of the formulation in delaying tumor growth clearly demonstrates
the importance of this delivery system in maintaining an inhibitory level of drug over a long
period of time.
Description
Editorial Note:
2021104207
First page of drawings submitted added to the description. Description is now 7 pages.
TITLE OF INVENTION HALLOYSITE NANOTUBE AS A MODIFIED DRUG RELEASE CARRIER FOR 6 MERCAPTOPURINE
Cancer is wide group of diseases which could start practically from any, part of the human body, when atypical cell grows ungovernably and yonder their partition to berate adjoining parts of the human body and outspread to other organs. This hindmost activity is called metastasizing and is the extensive cause of death from cancer. Although is this fast-growing world cancer is the 2nd largest paramount cause of death across the world, conceding for an approximate 9.6 million lives', which is one in six deaths, in 2018 lung, prostrate, colorectal, stomach, and liver cancer were the most regular types of cancer in males, though on other hand breast, colorectal, lung, cervical, and thyroid cancer were the most regular among females. However, Cancer could affect one an all young or old, rich or poor, men or women, even children's to are affected which constitutes an enormous burden for patient, families, and societies. Being one of the paramount causes of deaths worldwide. Though many in these deaths can be circumvented, between 30-50% of cancer are preventable aerobicized life style choices such as illusion of tobacco & by accepting public health measures like inoculation against cancer generating infection other can be spotted early, which could be served and rehabilitated. Even with later phase of cancer, the endurance of patients should be pleased with adequate palliative care. Cancer is the disease that transpire due to the variance in the cell cycle of the body, under normal condition the cell cycle is very highly regulated as the number of new cells formed by cell cycle is just adequate enough to replace the old cells which have undergone apoptosis or have died due to cell injury or some other cause 6-Mercaptopurine an antineoplastic agent loaded with in a Nano particulate carrier system HNTs were prepared by ultra-sonication and vacuum filtration method and coated with pH responsive polymer Eudragit s-100 by magnetic stirring and centrifugation technique for developing a pH responsive formulation, for delivering sustained release formulation. The present study includes identification, formulation, and evolution of 6- Mercaptopurine loaded
HNTs a Nano particulate carrier system. Formulation developed in this work was aimed to increase the bio availability of 6-Mercaptopurine with short biological half-life and delivering appropriate amount of drug in the systemic circulation on the cancerous cells without effecting normal cells by achieving sustained release formulation.
SUMMARY Delivery of antineoplastic agents by using nano particulate carrier system by using Halloysite nano tube (HNTs) which is a Nano particulate carrier system is a new strategy with enhanced potential to accelerate anti-cancer effect of the 6-Mercaptopurine by enhancing its bioavailability and reducing the systemic toxicity. In this study we have developed a formulation using HNT as a carrier of 6-Mercaptopurine which is an antineoplastic drug which serves shorter half-life as a result of which large part of delivered drug are been excreted out from the body in un changed form through urine, to avoid this adverse effect by increasing the bioavailability of the drug at the cancer sight have been demonstrated. The primary objective of this work was to prepare and evaluate the sustained release of 6- Mercaptopurine using HNTs as a carrier system followed by coating the same with Eudragit s-100 Co-polymer for achieving pH dependent sustained release of drug. Pure HNTs were functionalizes and drug incorporation within the halloysite lumen was achieved by Ultrasonication and vacuum filtration method. Identification test were carried out by using different techniques like melting point determination, partition coefficient and FTIR. The prepared formulation was evaluated for different parameters like Drug entrapment efficiency which was found to be maximum, Drug excipients compatibility studies, In vitro studies and particle size determination. FTIR studies proved that there was no interaction between drug and excipients, particle size determination was carried out through SEM showing the micro ranges between (6.73ptm-19.3ptm) respectively. Drugreleasedwascarriedoutfor20hrs.inphosphatebufferPh7.4at37Canmaximumrelease was found to be 89.56% for formulation Fl. The formulation F1 showed 21.81% tumor growth inhibition. Hens it was concluded that the prepared formulation possessing Sustained release, improving the bioavailability and improved % tumor growth inhibition of 6-MP which could be more efficient in treatment of cancer and can be considered as novel drug deliverysystem.
The conventional oral dosage forms are endorsed on to command over Drug delivery, resulting in variations of plasma drug level. Different approaches have been carried out to prevent the release of drug in stomach from the oral dosage form.Development of pH dependent formulation is the greatest approach to reduce the disadvantage of oral dosage form as the drug delivery depends on the pH of environment.The Drug releases gradually from nano particulate carrier system (HNTS) at wanted rate resulting gastric residence time with tempering in fluctuation in plasma drug concentration.Halloysite nano tube a carrier used have large surface area for drug loading resulting maximum drug loading and delivering sustained release of drug for longer interval.The goal of existing study is to develop a pH dependent formulation using nano particulate carrier system (HNTS) for sustained delivery of antineoplastic agent.
Reasons for the selection of drug: 1. 6-Mercaptopurine is a purine derivative and an antineoplastic compound having antimetabolite action.
2. This purine derivative also serves with a good immunosuppressant property due to which can also work against auto immune diseases. 3. This antineoplastic agent basically acts directly on process of protein synthesis which involves active participation of nucleus and DNA. 4. This novel antineoplastic agent has a good cure rate for the patients suffering from cancer.
Accompanying the above description, the method for performing this Invention consists of following steps. Drug loading within the Halloysite lumen
20pg of drug was weighed and dissolved in 4:1 v/v of ethanol and water solution (5ml) and considered as (A), now 20pg HNTs was taken in which 2.5 ml of ethanol and water solution (A) was added and considered as (B), this solution (B)was sonicated in solicitor for 30 minutes, this solution (B) was taken out andfiltered through vacuum filtration using 20-micron filter paper, the filtrate obtained on the filter paper was dried in oven at 37 0 C for 20 hrs. pure drug loaded HNTs were obtained. Coating of pure drug loaded HNTs with polymer Pure drug loaded HNTs was transferred to a solution of eudragitS-100 polymer and ethanol 3:1 ratio Halloysite polymer weight ratio the solution obtained was kept on magnetic stirrer using beaker and stirred of 24 hrs. using magnetic bead at room temperature the obtained mixture was centrifuged for 2 hrs. at 4000 rpm. Sediment and supernatant obtained were againdried in oven at 40 0 C for 24 hrs. to obtain thefinal formulation. SEM (Scanning Electron Microscopy) Scanning electron microscopy is used to study the particle count and size determination of the sample whether it's in a nano range.
In Vitro drug release Final obtained formulation was enclosed in dialysis membrane which was emerged in a releasing medium of phosphate buffer pH 7.4 for 20 hrs. at 370 c by using shake flask method. During this process exact volume of sample were taken out from the flask and simultaneal equal amount of buffer was added to the flask after each sampling. Further release profile of each sample was recorded under UV apparatus at standard X max.In vitro drug release of all the
formulation was preformed and percentage drug release was calculated respectivelyforeachformulationinphosphatebufferpH 7.4at37C. it wasobserved that formulation containing equal amount of drug and excipients possesses maximum drug release in formulation F1. Stability study
For conducting stability studies 3 best formulations were chosen and were analyzed according to ICH guidelines at different temperature and conditions. To analyze the stability of API within the formulation and stability of formulation itself. In-vitro cytotoxicity study of formulations:
The in vitro cytotoxicity of the CPT formulations was performed on the human breast cancer cell line MCF-7. The concentration of drug was 10 pg/ml used for in vitro studied. Sensitivity of MCF-7 cells to formulations was determined individually by the MTT colorimetric assay. Cells were seeded in a flat-bottomed 96-well plate and incubated for 24 h at 37°C and in 5% C02. The cell line was exposed to all formulations mentioned above. The solvent DMSO treated cells served as control. Cells were then treated with MTT reagents (20[t/well) for 4 h at 37°C and then, DMSO (200[l) was added to each well to dissolve the formazan crystals. The optical density was recorded at 492 nm in a microplate reader. Percentage of residual cell viability was determined as (1-(OD of treated cells/OD of control cells)) x100. The drug show 12.34 % tumor growth inhibition and the formulation F1 showed2l.82% tumor growth inhibition, the formulation F1 has maximum% tumor growth inhibition. Formulation F2,F3 and F4 showed 16.72, 19.11, 18.17 % tumor growth inhibitionrespectively. Formulation F1 showed maximum % tumor growth inhibition due to maximum drug release from the HNTs formulation.
CONCLUSION Local deliveries of chemotherapeutic agent by controlled release polymers are a new strategy with the potential to maximize the anti-tumor effect of a drug and reduce systemic toxicity. In this study, we have demonstrated the effectiveness of using the biodegradable chitosan polymer to deliver high doses of 6-Mercaptopurine locally to a mouse tumor model. Growth of tumors treated in this fashion was retarded for significantly longer periods than were tumors treated with systemically administered 6-Mercaptopurine. 6-Mercaptopurine delivered by intra-tumoral hydrogel showed no toxicity. Delivery of antineoplastic agents by using nano particulate carrier system by using Halloysite nano tube (HNTs) which is a Nano particulate carrier system is a new strategy with enhanced potential to accelerate anti-cancer effect of the 6-Mercaptopurine by enhancing its bioavailability and reducing the systemic toxicity. In this study we have developed a formulation using HNT as a carrier of 6-Mercaptopurine which is an antineoplastic drug which serves shorter half-life as a result of which large part of delivered drug are been excreted out from the body in un changed form through urine, to avoid this adverse effect by increasing the bioavailability of the drug at the cancer sight have beendemonstrated. The primary objective of this work was to prepare and evaluate the sustained release of 6 Mercaptopurine using HNTs as a carrier system followed by coating the same with Eudragit s 100 Co-polymer for achieving pH dependent sustained release of drug. Pure HNTs were functionalizes and drug incorporation within the halloysite lumen was achieved by Ultrasonication and vacuum filtration method. For achieving the incorporation of drug within the Halloysite lumen, Drug and ethanol solution was prepared this solution was added to pure weighed HNTs and was sonicated the obtained solution was filtered using vacuum filter by placing micron filter paper the filtrate obtained was dried in oven. Drug entrapment efficiency was not much but was considerable though Formulation F1 showed maximum entrapment efficiency with drug entrapment 78.43%. Particle size determination showed that the formulated product was in micro range and coating on the surface was been clearly observed. Although all the formulation showed sustained released of the drug when investigated of 20 hrs.in phosphate buffer pH 7.4. Formulation Fl, F2, F3 and F4 showed percentage drug release which was about 89.56, 74.36, 75.13 and 75.74% respectively. Which showed that formulation with higher entrapment efficiency possess maximum percentage drug release.
BRIEF DESCRIPTION OF THE DRAWINGS: Fig.1: Depicting size and coating of drug loaded HNTs with Eudragit s-100 co- polymer Fig2. (F1) Depicting coating of HNTs with eudeagits-100 Fig3. (F1) Image of a single coated HNT Fig4. In-vitro drug release of formulation, the % cumulative drug release data Fig5. % Tumor growth inhibition
Table. Percentage cumulative drug release of formulation Table2. Stability studies of formulations
Figures:
Editorial Note:
2021104207
Only 1 page of claim
Claims (6)
- WE CLAIM 1. A halloysite nanotube which is a modified drug release carrier for 6-mercaptopurine, thisformulation shows better effect on MCF-7 cell line.
- 2. It has less toxicity on normal cell.
- 3. Formulation claimed in 1 has localized drug delivery hence increased therapeutic efficacy and reduced side effects& has reduced frequency of administration.
- 4. Formulation claimed in 1 has site-specific drug delivery lower dose is required and is cost effective also.
- 5. Formulation claimed in 1 has improved bioavailability at the sight of action.
- 6. We claim the method for preparing formulation as described in claim 1 a) Drug loading within the Halloysite lumen b) Coating of pure drug loaded HNTs with polymer c) In Vitro drug release was evaluated d) Then stability studies were performed e) In-vitro cytotoxicity study of formulations was done.Editorial Note:2021104207Only 4 pages of drawingsFig1. (F1) Depicting size and coating of drug loaded HNTs with Eudragit s- 100 co- polymerFig2. (F1)Depicting coating of HNTs with eudeagits-100Fig3. (F1) Image of a single coated HNT100.0090.0080.0070.00 % drug release60.0050.0040.0030.0020.0010.000.00 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20F1 F2 F3 F4Fig4. In-vitro drug release of formulation, the % cumulative drug release data21.82 %Tumor growth inhibition20 19.11 18.17 16.7215 12.34 20211042071050 6-MP F1 F2 F3 F4Fig5. % Tumor growth inhibitionTable1. Percentage cumulative drug release of formulation Time (Hrs) F1 F2 F3 F4 1 11.79 13.97 14.36 11.92 2 14.10 17.56 20.13 13.84 3 15.51 20.26 22.82 25.38 4 17.18 23.59 27.44 26.02 5 22.82 27.44 30.51 27.43 6 25.00 33.85 32.31 34.35 7 28.72 37.69 33.85 37.82 8 31.15 41.67 35.26 40.25 9 35.00 46.41 37.95 46.53 10 39.10 48.46 38.85 51.66 11 45.90 53.33 41.15 54.87 12 51.03 56.15 45.90 58.33 13 56.28 59.36 48.33 61.28 14 61.67 61.28 53.21 67.69 15 66.54 63.72 57.95 69.94 16 72.05 65.13 62.31 70.51 17 77.82 67.18 65.13 72.92 18 84.10 71.15 68.08 73.33 19 87.33 73.59 72.56 75.35 20 89.56 74.36 75.13 75.74Table2.Stability studies of formulationsFormulation Storage conditions (%) Percent drug content code 7 Days 15 Days 30 Days 60 Days 90 Days 5±30C 96.83 92.38 88.19 87.32 87.08 2021104207F1 25±20C / 60±5% RH 97.75 93.95 89.88 88.81 88.16 40±20C / 75±5% RH 97.66 93.34 89.25 89.03 86.48 5±30C 98.26 96.34 94.48 92.57 91.73 F2 25±20C / 60±5% RH 98.11 95.24 93.54 93.11 92.41 40±20C / 75±5% RH 97.94 96.44 92.43 90.24 89.92 5±30C 99.56 98.68 98.57 96.38 94.19 F3 25±20C / 60±5% RH 97.47 98.46 96.47 94.27 92.71 0 40±2 C / 75±5% RH 97.31 95.36 95.22 94.95 91.51 5±30C 98.68 98.64 96.68 94.10 93.91 F4 25±20C / 60±5% RH 98.57 97.35 95.75 94.92 92.20 40±20C / 75±5% RH 97.85 97.33 96.58 94.85 91.24
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2021104207A AU2021104207A4 (en) | 2021-07-15 | 2021-07-15 | Halloysite nanotube as a modified drug release carrier for 6-mercaptopurine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2021104207A AU2021104207A4 (en) | 2021-07-15 | 2021-07-15 | Halloysite nanotube as a modified drug release carrier for 6-mercaptopurine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2021104207A4 true AU2021104207A4 (en) | 2021-09-09 |
Family
ID=77589177
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2021104207A Ceased AU2021104207A4 (en) | 2021-07-15 | 2021-07-15 | Halloysite nanotube as a modified drug release carrier for 6-mercaptopurine |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU2021104207A4 (en) |
-
2021
- 2021-07-15 AU AU2021104207A patent/AU2021104207A4/en not_active Ceased
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5709354B2 (en) | Treatment of cancer patients with mTOR inhibitors | |
| DE69928093T2 (en) | COMBINATION PREPARATION CONTAINING MONOCYTE-DERIVED CELLS FOR THE TREATMENT OF NEOPLASTIC OR INFECTIOUS ILLNESSES | |
| RU2432164C2 (en) | AQUEOUS SOLUTION OF PHARMACEUTICAL COMPOSITION OF 20(R)-GINSENOSIDE Rg3 AND METHOD FOR PREPARING IT | |
| HUE035101T2 (en) | Cancer Cell Targeting Using Nanoparticles | |
| EA011612B1 (en) | Irinotecan preparation | |
| KR101530393B1 (en) | Agent for treatment of pulmonary disease | |
| CN112826808B (en) | Neutral/cation mixed lipid nano preparation of cyclic dinucleotide or analogue thereof and application thereof | |
| US20190307794A1 (en) | Method for inducing transdifferentiation of immune cells based on exosomes | |
| JP2003501379A (en) | Use of Drug-Filled Nanoparticles for Cancer Treatment | |
| JP6038486B2 (en) | Drugs and nutritional supplements containing Taiwan Green Propolis Extract | |
| AU2021104207A4 (en) | Halloysite nanotube as a modified drug release carrier for 6-mercaptopurine | |
| JPS63183528A (en) | Malignant tumor remedy | |
| WO2021096464A1 (en) | A novel nanotechnologic approach to glioblastoma treatment with solid lipid carriers | |
| CN103154012B (en) | The sugared dendrimer of poly-propyl ether imines | |
| JP2020169146A (en) | Agent for enhancing antitumor effect of polymer type anticancer agent | |
| JPH01233219A (en) | Carcinostatic agent composition | |
| RU2670091C1 (en) | Method for delivering nanoparticles intended for the transport of drugs to the brain of mammals through the blood-brain barrier | |
| JP3014148B2 (en) | Malignant tumor recurrence inhibitor | |
| EP1372636B1 (en) | Metronomic dosing of taxanes for inhibiting tumor growth | |
| CN114276390B (en) | Dithiocarbamate derivative nano-drug for anti-tumor drug delivery, and preparation method and application thereof | |
| EP0819136B1 (en) | Mdp derivatives and conjugates having haematopoietic function stimulating activity, and compositions containing same | |
| FR2535609A1 (en) | ANTITUMOR ACTION MEDICINE BASED ON POLYHEXAMETHYLENEGUANIDINE | |
| EP4382134A1 (en) | Pharmaceutical composition for preventing or treating triple-negative breast cancer, comprising oligonucleotide as active ingredient | |
| CN116327782B (en) | Bone-targeted co-delivery bortezomib and pomalidomide nanocomposite as well as preparation method and application thereof | |
| Cremers et al. | Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |