A Review of the Novel Drug Delivery System used in the Treatment of Cancer

 

Kanti Sahu*, Rishita Pathak, Naveen Agrawal, Pinkesh Banjare, Harish Sharma,  Gyanesh Sahu

Shri Shankaracharya Technical Campus, Shri Shankaracharya Group of Institutions, Faculty of Pharmaceutical Sciences, Junwani, Bhilai, Dist-Durg (C.G.) India.

 

ABSTRACT:

Cancer is a major public health problem and a main cause of death worldwide. Cancer is a main health problem in world that causes ‘morbidity and mortality’ in both children and adults. Novel drug delivery strategies are needed to meet the complex challenges associated to cancer therapy. Chemotherapy is a first-line treatment for higher stage of cancer. Liposomes provide a platform to carefully include and transport different therapeutic agents across the human body with sufficient blood motion time. The discovery liposomes have been widely used in biomedical research. Liposomes is slow and uncontrolled, resulting in sublethal concentrations of free drug in the tumor and poor therapeutic efficacy. Nanoparticles also play a important role in diagnostic and treatment of bioavailability, optimize pharmacokinetics, and decrease dosing constancy of drugs and genes. Nanotechnology is an originate and assuring field that uses nanoparticles (NPs) to promote the examination and treatment of cancer. Cancer. Drug delivery systems beyond the nano, micro, and macroscales can extend half-life, improve.

 

 

 

INTRODUCTION:

Drug delivery system:

Drugs have been used around history to aid in the treatment of illnesses that plagued the populace of the period. During this time frame, adjustments were made to drugs and their related delivery systems, improving their bioavailability and potency [1]. Drug delivery systems are substance designed to modify the biological behaviour of the pharmaceutical active ingredients that they carry in order to afford more beneficial bio-distribution and safety profiles [2].

 

 

Colloidal drug delivery systems (CDDS) consist of lipid, natural or synthetic polymer particles, such as liposomes, solid lipid nanoparticles (SLN), poly D, L-lactide (PLA) or poly D, L-lactide-co-glycolide (PLGA) nanoparticles (NP), micelles, etc., encapsulating drugs, nucleic acids or plasmids [3].

 

Novel drug delivery system are required to meet the complex challenges related to cancer therapy. Biocompatible pH-sensitive drug delivery nanocarriers based on amphiphilic copolymers seem to be promising for cancer treatment [4]. The purpose of drug delivery systems is to expand the therapeutic efficacy of the joined drug (s) by the means of bioavailability enhancement or minimization of adverse effects. Therapeutic goals with any drug therapy, the delivery system or dosage system must be capable to secure the therapeutic plasma levels immediately and further maintenance of these levels for the prolonged of therapy [5]. Drug delivery systems beyond the nano, micro, and macroscales can extend half-life, improve bioavailability, optimize pharmaco-kinetics, and decrease dosing constancy of drugs and genes [6].

 

Cancer:

Cancer is a major public health problem and a main cause of death worldwide, currently believe the lives of almost 9 million people a year [7]. Cancer is a main health problem in world that causes ‘morbidity and mortality’ in both children and adults. Cancer appear from the uncontrolled growth and survival of modify or transformed cells [8]. As one of the most common planning for the treatment of cancer, chemotherapy remains unsatisfactory due to the low targeting ability and dangerous adverse effects of anti-cancer drugs [9]. Chemotherapy is a first-line treatment for higher stage of lung cancer in which chemotherapeutic drugs are usually administered intravenously for systemic circulation. The use of chemotherapeutic drug is based on the principle of toxic compounds to inhibit the reproduction of cells growing at an abnormal rate [10].

 

Few anticancer drugs have the ability of self targeting, trapping the drug in a particular carrier, thereby delegating the tumor-targeting responsibility to the transporter, is an established planning to achieve this goal [11].

 

Novel drug delivery system:

The goal of an ideal drug delivery system is to deliver a drug to a specific site and in specific time and release pattern. Drug delivery technologies modify drug release profile, absorption, and distribution improving product efficacy and safety [12]. The improvement of biodegradable/biocompatible materials and novel drug delivery systems (DDSs) represents a reformation in medicine over the years and initial to considerable improvements in other biomedical domains including biomaterials science and tissue engineering, while developing interdisciplinary association among chemists, biologists, clinicians, and engineers [13].

 

Novel drug delivery planning are needed to satisfy the complex challenges associated to cancer therapy. Novel drug delivery system are the process that required to face the multiple test to interaction to cancer therapy. Biocompatible pH-sensitive drug delivery nanocarriers based on amphiphilic copolymers seem to be encouraging for cancer treatment [14]. Novel type of drug delivery system have some advancement such as fast onset of action, administered without water, instantly releasing the drug, better bioavailability and better patients compliance is preferable for convenient and easy administered dosage form [15-16].

 

 

Fig 1: Types of cancer

 

 

Fig 2: Types of novel drug delivery system

 

Liposome:

Liposomes are small artificial vesicles of rounded shape with a membrane composed of phospholipid bilayers. They can be made of natural nontoxic phospholipids and cholesterol in the form of one or multiple concentric bilayers capable of encapsulating hydrophilic and hydrophobic drug [17]. Size of liposome can differ from very small (25 nm) to large (2.5 μm) vesicles [18]. Liposomes provide a platform to carefully include and transport different therapeutic agents across the human body with sufficient blood motion time [19]. Liposomes have been widely applied owing to their well-known advantages. Moreover, they can remain in the circulation for prolonged time periods after surface           modification [20].

 

Liposome has been used as a drug transporter to reduce a toxicity and increase a therapeutic efficacy In addition, the liposome is able to enhance the encapsulation ability of a poorly soluble drug, improve its bioavailability, deliver drugs to the target site, and achieve a controlled release [21]. Liposomes for systemic cancer therapy are generally designed for stability in the motion and therefore contain their cargo until uptake by cells. Consequently, drug release from these liposomes is slow and uncontrolled, resulting in sublethal concentrations of free drug in the tumor and poor therapeutic efficacy [22].

 

Liposome based Drug used in treatment of cancer

S. No.	Polymer	Drug	Outcome	Reference
1.	redox-sensitive oligopeptide	Paclitaxel (PTX), (PTX/siRNA/ SS-L)	PTX/siRNA/SS-L not only exhibited the most powerful effect on suppressing tumor growth, but also significantly restricted pulmonary Metastasis. The combination of PTX and anti-survivin siRNA is a promising strategy to synergistically inhibit breast tumor growth and metastasis, and the redox-sensitive oligopeptide liposomes may be a potent drug nanocarrier for combined cancer therapy.	[23]
2.	Methacrylate ester copolymers	oxalipatin	Oral administration of these liposomes encapsulated alginate beads containing L-OHP may significantly improve patient compliance by reducing dosing frequency from conventional doses and help in better management of cancer chemotherapy.	[24]
3.	polyethylene glycol	glucose oxidase (GOx), banoxantrone dihydro-chloride,	in vivo PA imaging, such liposome-GOx could specifically block tumorous glucose supply, exhaust tumorous oxygen for hypoxia enhancement, and produce toxic H2O2 inside the tumors. In the meanwhile, liposome-AQ4N once inside the tumor with enhanced hypoxia would be further activated to achieve strong synergistic antitumor effect.	[25]
4.	Dextran sulfate and alginate, AL-CIS complex	Doxorubicin, cisplatin	The co-delivery of DOX and CIS resulted in a synergistic cytotoxic effect in MCF-7 and MDA-MB-231 breast cancer cells. Specifically, treatment with ligand targeted TL-DDAC resulted in a significantly higher cytotoxic effect in the cancer cells compared to treatment with the individual drugs. The presence of CIS could increase the cytotoxic potential of DOX by inducing more apoptosis in cancer cells.	[26]
5.	N-(carbamoyl-methoxypolyethylene glycol 2000)-1,2- Distearoyl snglycerol -3-phosphoethanolamine	Mitomycin C lipophilic prodrug (MLP) and doxorubicin (DOX)	liposomes also have significant in vivo challenges such as reaching extravascular targets, and penetrating uniformly tumors, and their added clinical value remains uncertain. One aspect of PSMA targeting that may be helpful, is the expression of PSMA in the neovasculature of many tumors other than prostate cancer, which could facilitate targeting without the need for liposome extravasation, and thereby increasetargeted drug delivery and therapeutic activity.	[27]

 

Liposome used in cancer therapy:

Since the discovery liposome have been widely used in biomedical research. The ability to enclose a wide variety of small molecules, as well as biopolymers, such as nucleic acids and proteins, their high bio-compatibility, low toxicity, tenable size and lipid composition made liposome a rare transporter for the delivery of bioactive compounds to pathological cells and tumors [28]. The liposome has been express to be a approaching alternative for anticancer activity and one of the most biocompatible vesicular drug carriers with a capacity for cooperative hydrophilic and hydrophobic compounds [29].

 

 

Liposomes have been largely studied as nanocarrier advantage from the special structure consisting of a lipid bilayer and aqueous inner cavity. The biochemical format of liposome is very related to that of human cell membrane which makes liposome have good biocompatibility and low irritation to human body [30]. Liposomes have been commonly applied owing to their well-known advantages. Moreover, they can continue in the circulation for prolonged time periods after surface Modification [20].

 

 

 

 

 

 

Marketed preparation:

  

Fig 3: liposomal based marketed preparation

 

Nanoparticles:

Nanotechnology is the branch of multidisciplinary science and positively impacts the human life aspects [31]. Nanoparticles have a size of 10-1000 nm. In microsystem the drugs are dissolved, entrapped, encapsulated, or attached to a nanoparticle matrix [32]. Nanoparticles also play a important role in diagnostic and treatment of Cancer [33]. Their size and shape can be tailored as needed, Drug that are formulated in nano preparation they shoe good bioavailability, reduced toxicity and it give desirable pharmacokinetic and patient compliance [34]. Nanoparticles are one of the mostly studied vehicles in drug delivery. Poly (lactic-co-glycolic-acid) (PLGA) is one of the polymers most used to produce nanoparticles [35].

 

NPs have the ability to offer solutions to the current difficulty in cancer therapies, because of their unique size (i.e. general 1–1000 nm or at least one dimension sized from 1 to 100 nm, 5–200 nm range for medical purpose) and large surface-to-volume ratios [36]. Nanoparticles prepared from natural or synthetic polymers are colloidal transporter with dimensions on the nano scale (10−9 m) particularly agreeable to transport a wide variety of therapeutic molecules for cancer treatment, from small chemical drugs to biological macro-molecules [37].

 

Nanoparticles based Drug used in treatment of cancer:

S. No.	Polymer	Drug	Outcome	Reference
1.	Poly (ethylene glycol)-ε-poly(caprolactone) (PEG-PCL)	Doxil, doxorubicin	Sufficient for the inhibition of CRC metastasis growth or complete elimination of CRC lung metastases without deleterious effects on normal lung, liver or kidney tissues.	[38]
2.	Poly(lactide-co-glycolide) (PLGA), D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS),	Cre-advenovirus CaCl2,	Both in vivo and in vitro studies support the proposed intercellular transportation of NP from MSC to cancer cells.	[39]
3.	Polycaprolactone	Docetaxel	the FA-RES+DTX nanoparticle combination could be effective in treating DTX -resistant and folate receptor expressing cancers.	[40]
4.	Hydrophilic or zwitterionic polymers such as polyethylene glycol (PEG), polysaccharides and phosphorylcholine-based polymers	Doxorubicin	In vitro and in vivo experiments demonstrate that DOX-loaded HES-PDA NPs can effectively suppress the growth of liver cancer, with a tumor inhibition rate of 73.1%, and significantly alleviate the side effect associated with DOX.	[41]
5.	Amphiphilic copolymers	Quercetin	The colorimetric MTT assay showed that blank nanoparticles did not reduce cell viability of the tested cells.	[42]

 

Nanoparticles used in cancer therapy:

Nanotechnology is an originate and assuring field that uses nanoparticles (NPs) to promote the examination and treatment of cancer [43]. Nanotechnology, which has grown rapidly in recent years, greatly dispense to progress in medical fields including cancer therapy about improvement in drug delivery systems [44]. Nanotechnologies promise new treatment approaches for patients with metastatic cancer. The US Food and Drug Administration approved the first such treatment, Doxil, which is the chemotherapy drug doxorubicin packaged in a lipid nanoparticle[45].The static delivery of nanoparticles faces several key challenges, such as enhanced reticulo-endothelial system uptake and a reduced permeability and holding effects and, to date, not demonstrated development in survival compared to standard drug, i.e. paclitaxel, and exhibit greater neurologic and hematologic toxicity[46].

 

The biosynthesis of nanoparticles, which produce a more effective, rapid and eco-friendly technique to the synthesis of nanoparticles, reducing or completely eliminating the use of high temperatures, pressures, toxic chemicals, space, and capital required to set up equipment and heavy machinery required for the physical and chemical approaches to synthesis[47].

 

Marketed preparatation:

  

Fig 4: nanoparticle based marketed preparation

Role of Phytoconstituents in the treatment of Cancer:

The practice of herbal medicines is carried out since centuries. There is a growing interest in improving the bioavailability of a large number of potent drugs by combining it with natural bioenhancers [48-50]. The concept of ‘bioavailability enhancers’ of natural origin has been obtained from the ancient knowledge of Ayurveda system of medicine [51]. The use of natural bio enhancers has gained importance in the current scenario to improve the pharmacokinetic parameters and hence bioavailability of various potent drugs [52-53].

 

The various mechanisms by which natural bio enhancers act are:

a)   Decrease in hydrochloric acid secretion and increase in gastrointestinal blood supply,

b)   Hinder the gastrointestinal transit, gastric emptying time and intestinal motility,

c)   Modifications in the permeability of the GIT epithelial cell membrane,

d)   Cholagogous effect,

e)   Bioenergetics and thermogenic properties

f)   Suppression of first pass metabolism and inhibiting drug metabolizing enzymes and stimulation of the activity of gamma glutamyl transpeptidase (GGT) enzyme which enhances the uptake of amino acids [54-60].

Phytoconstituents used for cancer therapy:

S.No	Drug	Polymer	Phytoconstituent	Outcome	Reference
1	Phosphatidylcholine, 3,4-dihydroxy-L-phenylalanine	lecithin (LEC) or Phospholipon	Asparagus racemosus	The entrapment efficiency and in vitro tyrosinase inhibitory activity were 42.19%-69.08% and 12.06%-25.00%. Types of lipid and preparation methods significantly influenced the physico-chemical properties of liposomes such as vesicle type, size, surface charge, drug entrapment, and biological activity.	61
2	Carbopol 940, Diclofenac sodium	Polyethylene glycol-400 (PEG-400), propylene glycol	Quercetin	The optimized formulation showed improved physicochemical stability, acceptable mechanical properties and enhanced skin permeability thus increasing the therapeutic efficacy, as revealed by its antiarthritic activity.	62
3	Cyclosporine, cyclophosphamide and ampoxin	Polyethelene glycol 400 (PEG 400)	Quercetin	in vivo experiment results revealed improved efficacy of QCT-CS NPs over free QCT in reducing tumour size of mice bearing lung and breast tumour xenograft.	63
4	Dimethyl sulfoxide	Chitosan and Pluronic F 68	Curcumin, Rutin	prepared nanoparticles have shown sustained release of both these drugs up to 12 h. nanoparticles can be an excellent tool with these combinational drugs which can be used in treating multi-drug resistance cancers	64
5	Azo bis isobutyronitrile (AIBN), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxy succinimide (NHS),	Chitosan	Curcumin	The MTT assay and optical micrographs of the treated and untreated curcumin-loaded TRC-NPs with L929 and PC3 cells were analyzed at 35.C (below LCST) and 38.C (above LCST), and the morphological change has been observed only with PC3-treated curcumin- loaded TRC-NPs, at 38 *C which shows that the release mechanism is only through the LCST of the carrier. curcumin-loaded TRC-NPs could be more beneficial for cancer treatment by a proper combination therapy with hyperthermia.	65
6	soy phosphatidylcholine	Poly (lactic-co-glycolic acid) (PLGA) and poloxamer (Pluronic F68® and Pluronic F127®)	Grandisin	Nanoencapsulation sustained GRAN release, provided chemical stability and altered its cytotoxicity.	66

 

CONCLUSION:

Cancer is a major health problem which effects a large part of the world population. Even after many experiment and research there is no permanent cure for cancer. The current treatment of cancer is not efficient because of the adverse effect of cytotoxic drugs. To overcome those problem Novel drug delivery system will come, which reduces dosing frequency and enhance the patient complain. The novel drug delivery systems like microspheres, nanoparticles, dendrimers, liposomes, and transdermal delivery are very promising. Drugs are given in low doses thus minimizing the chances of drug toxicity. Novel form of drug delivery can good for the society by providing drug release based on the changes of body. It reduce the need of high dose and dosing frequency as well as drug associated toxicity, which makes safe for the patient. In NDDS preparation phytoconstituents are used as a bio enhancer, which enhance the bioavailability of the potent drug and reduce the dosing frequency.

 

ACKNOWLEDGEMENT:

The corresponding author acknowledge the partial support and facilities provided by the Department of Pharmacy the guidance given by Mr. Gyanesh Sahu Professor of Pharmaceutical Science.

 

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Received on 12.04.2019         Modified on 18.05.2019

Accepted on 20.06.2019       ©A&V Publications All right reserved