Application of nanocarrier-based drug delivery system in treatment of oral cancer

Figures & data

Figure 1. Distribution of oral cancer in oral cavity.

Figure 2. Incidence and mortality of oral cancer in India.

Table 1. Chemotherapeutic agents used in treatment of oral cancer.

Name of drug	Category	Route of administration	Marketed preparation
Cetuximab	Monoclonal antibody	Parenteral	Erbitux^®
Cisplatin	Platinum containing alkylating agent	Parenteral	Platinol^®, Platinol^®-AQ
Docetaxel	Anti-mitotic chemotherapeutic agent	Parenteral	Taxotere^®
Fluorouracil	Pyrimidine analogue	Topical and parenteral	Adrucil (IV), Carac (topical), Efudex and Efudix (topical)
Methotrexate	Antimetabolites	Oral and parenteral	Methex^®

Table 2. Potential salivary biomarkers used for detection of oral cancer.

Type of salivary biomarker	Examples
Inorganic compounds	Na, Ca, F, Mg
Proteins and peptides	α-Amylase, IL-1, IL-6, IL-8, MMP-2, MMP-9, IGF-1, IL-1β
DNA and RNA	P53 gene codon 63, S100P, SAT
Metabolomic compounds	Amino acids-like tyrosine, alanine, serine, valine, phenylalanine
Miscellaneous	Telomerase activity

Na: sodium chloride; Ca: calcium; F: fluorine; Mg: magnesium; IL: interlukine, MMP: matrix metalloproteinase; IGF: immunoglobulin factor; SAT: satellite.

Figure 3. Types of nanoparticles.

Table 3. Examples of various nanocarriers used in oral cancer.

Name of drug and its structure	Polymer	System	Purpose	References
Paclitaxel	Albumin	SLNs	Improvement of therapeutic efficiency	[27–29]
	Eudragit	Polymeric nanoparticles	Enhanced drug delivery, improvement in pharmacokinetic properties
	CDs	Polymeric nanoparticles	Increased drug-loading capacity
	PLGA-PEG	Polymeric nanoparticles	Targeted lymphatic delivery
		Niosomes	Slow drug release with reduced toxic side effects
		NLCs	Targeted drug delivery
Cisplatin	PEG-poly Glutamic acid copolymer	Polymeric nanoparticles	Treatment of carcinoma	[30]
	Cyclodextrin	Inclusion complex	Increase in solubility, improvement in dissolution rate and reduction of toxicity
		Dendrimers	Targeted drug delivery
Docetaxel	PLA-PEG block polymer	Polymeric nanoparticles	Targeted drug delivery	[31,32]
	CDs	Polymeric nanoparticles	Increased solubility and prolonged release
Methotrexate	PLA-PEG block polymer	Polymeric nanoparticles	Enhanced anti-tumor activity	[33,34]
	Cyclodextrin	Inclusion complex	Enhancement of aqueous solubility and bioavailability
	Cyclodextrin	Niosomes	Increased entrapment efficiency and solubility
5-Fluorouracil	PVA	Microspheres	Enhanced anti-tumor activity	[35]
	Cyclodextrin	Inclusion complex	Enhancement of Solubility

PLGA: poly(lactic-co-glycolic acid); PEG: polyethylene glycol; PLA: polylactic acid; PVA: polyvinyl alcohol.

Table 4. Some patents in the area of oral anticancer drugs for oral therapeutics.

Patent number	Assignee	Year	Therapeutic agent	Disease	Invention	Reference
WO2016020697 A1	Cipla Limited, King, Lawrence	2016	–	Cancer	Disclosed the development and composition for polymeric NPs used for the treatment of cancer	[36]
US9393201 B2	JW Pharmaceutical Corporation	2016	Oxaliplatin	Cancer	Investigation disclosed the composition and development method for oxaliplatin-loaded nanoparticle by emulsification method for oral administration	[37]
WO2015023797 A9	Northwestern University	2015	–	Cancer	Reported the NLCs comprising lipid layer with lipoprotein which showed the potential in the drug delivery application for the treatment of cancer, infectious disease, vascular disease	[38]
US20150140109 A1	Unichempharm Ltd, Oy Filana Ltd	2015	Docetaxel	Cancer	Disclosed the therapeutic activity and the composition of docetaxel-loaded biodegradable nanoparticle. It comprising PLGA, serum albumin and d-mannitol for the development of NPs and it suggested for development of enterosoluble tablets, capsules granules, powder, or in any other peroral form.	[39]
US9023395 B2	University of North Texas Health Science Center at Fort Worth	2015	–	Cancer	Disclosed the composition and development method for the polymeric NPs for controlled drug delivery application. It comprising use of biodegradable polymer along with stabilizing agents non-covalently linked with space electrophilic compound which react with nucleophilic agent on the site of action and place the targeting agent on the outside surface of a biodegradable nanocarrier for the effective treatment.	[40]
US 8,911,786 B2	Abraxis Bioscience, LLC, Los Angeles, CA, USA	2014	Rapamycin	Cancer	Disclosed the method of treatment, stabilizing, preventing, and improvement in the treatment of cancer by using rapamycin-loaded NPs.	[41]
US8784895 B2	Northwestern University	2014	Gold, silver, iron oxide	Cancer, bacterial infections	Investigation comprising metallic nanoparticle of 1–100 nm coated with polydopamine. Gold, silver or iron oxide was used as metallic therapeutic agent. Other agents also bound on it such as ligands, antibodies or imaging agents. These NPs revealed the use in the effective treatment of cancer, bacterial infections and as a diagnostic imaging.	[42]
WO2013171382 A1	Oy Filana Ltd	2013	Docetaxel	Cancer	Disclosed the therapeutic activity of docetaxel-loaded NPs comprising PLGA, serum albumin and d-mannitol. The prepared NPs were proposed for development of enterosoluble tablets, capsules granules powder.	[43]
EP2648760 A2	The Johns Hopkins University	2013	Curcumin, doxorubicin	Cancer	Invented the polymeric nanoparticle loaded with curcumin and doxorubicin along with modified shell surface to overcome the multidrug resistance to cancer chemotherapeutics and treatment-related systemic toxicity. The shell surface modification were done by using NIPAAM, AA and one vinyl monomer were chosen from the group of vinyl acetate, 4-vinyl benzoic acid, methylmethacrylate, vinylmethacrylate, N-vinylpyrrolidone, N-vinyl piperidone, N-vinyl caprolacum, N-vinyl carbazole, and styrene. While NIPAAM, the AA, and the vinyl monomer are taken in the molar ratios of 50–70:10–30:10–30. These finding revealed that NPs effectively overcome multidrug resistance and ameliorate cardiomyopathy in vivo	[44]
US8242165 B2	Creighton University	2012	Gemcitabine, taxanes, hydrophobic agents	Cancer	Disclosed the composition and preparation method of mucoadhesive NPs. These NPs comprising therapeutic agent along with glyceryl monooleate or monolinoleate (or other mono fatty acid ester) and chitosan as a mucoadhesive natural polymer. Investigation also disclosed the technique of pharmacotherapy for breast, pancreatic, colon, prostate, and other cancers by parenterally, or administering such NPs.	[45]
WO2011034394 A2	Choongwae Pharma Corporation	2011	Oxaliplatin	Cancer	Disclosed the oxaliplatin-loaded NPs comprising solid lipid and surfactant missed in cosolvent and removed the solid lipid and cosolvent using supercritical fluid gas technology for oral application in the treatment of cancer	[46]
WO2007108618 A1	–	2007	–	Cancer	Reported the anticancer drug-loaded NPs comprising organic chelating polymer along with biologically active metals for improvement of drug permeation and retention. Results showed that prepared NPs showed promising nanocarrier for cancer therapy along with EPR effect. Additionally, invention disclosed the aqueous soluble organometallic particles with anticancer potential via the EPR effect.	[47]
WO2007086651 A1	–	2007	–	Cancer	Developed drug-loaded hydrophobic bile acid- conjugated hydrophilic chitosan oligosaccharide nanoparticles along with high drug-loading capacity. The result showed that NPs exhibits excellent cytotoxicity potential against cancer cells along with controlled drug-release pattern. The prepared NPs showed potential nanocarrier for cancer chemotherapy.	[48]
CA2513759 A1	The Research Foundation of State University of New York	2004	–	Cancer	Disclosed the method and compositions for photodynamic medication. It comprising therapeutic agent or dye enclapsulated ceramic NPs developed by micellar composition of the dye. Thereafter, it precipitated by using alkaline hydrolysis and these NPs were isolated by dialysis. The prepared NPs were found to be spherical, highly monodispersed and stable in aqueous vehicle. Irradiation with light of suitable wavelength of the photosensitizing drug entrapped inside nanoparticles exhibited the development of singlet oxygen, and these NPs showed potential in the treatment of cancer.	[49]
US005399363A	Eastman Kodak Company, Rochester, NY	1995	–	Cancer	Invented the dispersible particles comprising anticancer drug with surface modifier having particle size <1000 nm. The formulation exhibited improved therapeutics profile with established safety parameters administered via IV bolus injection	[50]

NPs: nanoparticles; NIPAAM: N-isopropylacryl amide; AA: acrylic acid; EPR: enhanced permeation and retention.

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