Emergence of liposome as targeted magic bullet for inflammatory disorders: current state of the art

Figures & data

Figure 1. Illustration of multifunctional liposomes.

Table 1. Current pharmacotherapy’s in inflammatory disorders.

Therapeutic classification	Therapeutic category	Therapeutic agent	Mechanism of action	Applicability	References
Non-biological agents	Glucocorticoids Calcineurin inhibitor Antimetabolite	Prednisone, methylprednisolone, DEX Cyclosporin Azathioprine Leflunomide Mycophenolate mofetil Methotrexate	Inhibit many processes involved in immune responses and inflammation Block T cell activation and IL-2 production Interfere with the synthesis of nucleic acids and cell proliferation	PS, RA RA and PS RA and PS	Rahman et al. (2015a,b)
Biological agents	Anticytokines	Anakinra Tocilizumab Infliximab, Adalimumab, Golimumab, certolizumab and etanercept	They direct against IL-1 receptor They inhibit the IL-6 signaling They inhibit T cell proliferation	RA RA PS, RA and IBD	Fiocchi (2015), Rahman et al. (2015a,b)
	Anti-cell surface ligands	Abatacept Rituximab and Crelizumab	It block CTLA4 Target CD20 and deplete B cells	RA RA	Rahman et al. (2012c)

PS: Psoriasis; IBD: inflammatory bowel disease; RA: Rheumatoid Arthritis; DEX: Dexamethasone.

Table 2. Therapeutic approaches of liposome as drug delivery in effective treatment of inflammatory disorders.

Liposome size	Loaded drugs	Ligand	Cancer cell type	Outcomes	References
90 nm	Combretastatin/ Doxorubicin	RGD peptide	Murine Melanoma (B16, B16 F10)	2-fold decrease in IC50 as compared to non-targeted liposomes	Noble et al. 2014
100 nm	Doxorubicin	RGD peptide	Murine colon carcinoma (C 26)	It received larger tumor growth inhibition and well uniform biodistribution as compared to non-targeted liposomes	Noble et al. 2014
116 nm	Paclitaxel	RGD peptide	Human ovarian (SKOV-3)	3-fold reduction in IC 50 in in vitro and modest enhancement of tumor growth inhibition in vivo	Noble et al. 2014
76 nm	Doxorubicin	RGD peptide	Murine colon carcinoma (C26)	Enhanced tumor growth inhibition in vivo as compared to non-targeted liposomes and free DOX	Noble et al. 2014
110 nm	Trastuzumab, Rituximab	mAb	Human breast (MCF-7, LCC6)	Enhanced 25-fold anticancer efficacy as compared to free drug	Akhter et al. 2013
56 nm	siRNA (Bcl-2)	mAb	Human B cell lymphoma	It exhibited greater efficient delivery of the oligonucleotides and induced apoptosis	Akhter et al. 2013
120–150 nm	Mitoxantrone	peptide	Human breast (MCF-7), Human ovarian (SKOV-3)	It enhanced 20-fold reduction in IC50 as compared to conventional liposomes	Akhter et al. 2013
134–154 nm	Irinotecan	Octreotide (peptide)	Human thyroid medullary carcinoma	Enhanced anticancer efficacy as compared to non-targeted liposomes	Akhter et al. 2013
115 nm	Ceramide	Transferrin	Human ovarian (A2780)	It received 2-fold higher reduction in tumor volume as compared to non-targeted liposomes	Akhter et al. 2011
129 nm	Cisplatin	Holo-transferrin	Human cisplatin resistant ovarian carcinoma	It received higher delivery of cisplatin into tumor drug resistant cells	Akhter et al. 2011
100 nm	Oxaliplatin	Transferrin	Mouse colon (C26)	It got 20% larger tumor accumulation of Pt	Akhter et al. 2011
120 nm	Doxorubicin	Transferrin	Human small lung carcinoma (SBC-3)	It founds 30% reduction in IC 50 and enhanced intracellular uptake reported	Akhter et al. 2011
Drug carrier	Loaded drugs	Targeting site	Psoriasis (In vitro/In vivo studies)	Outcomes	References
Liposome	Dithranol	Chemokines	Human	0.5% dithranol loaded liposome showed higher efficacy, minimum staining to skin and cloth as compared to commercial available 1.15% dithranol ointment.	Rahman et al. (2015a)
Liposomes gel	Dyphylline	cAMP	Mice skin	It showed higher skin permeation and targeted action as compared to Dyphylline solution.	Rahman et al. (2015a)
Liposome	MTX	De Nova pathways	Porcine skin	It founds 3–4 times higher MTX skin permeation to porcine skin as compared to conventional cream	Rahman et al. (2015a)
Elastic liposome	MTX	De Nova pathways	Human	0.25% deformable liposomal gel applied on 25 patients, it founds that higher permeation and PASI score reduced from 6.2 to 2.9 at the end of 10 week as compared to 1% MTX gel.	Rahman et al. (2015a)
Liposomes	Tretinoin (TRE)	Gene transcription	Human	It showed enhanced efficacy, and better patient compliance.	Rahman et al. (2015a)
Liposomes	Resveratrol	Targeting on ROS	N/A	It found higher encapsulation efficiency (92–96%) and sustained release found.	Rahman et al. (2015a)
Elastic liposomes	Resveratrol	Targeting on ROS	Porcine skin (In vitro)	It showed higher permeation in porcine skin and significant inhibition of ROS and lipid peroxidation in psoriasis.	Rahman et al. (2015a)
Liposomes and their size	Loaded drugs	Targeting site	Arthritic model	Outcomes	References
SUV, 100 nm	Clodronate	Macrophages (synovium)	Streptococcal cell wall induced arthritis in Lewis rat	Enhanced cellular uptake in synovium	Rahman et al. (2015b)
MLV, Upto several μm	Clodronate	Macrophages (synovium)	Adjuvant arthritis, AIA in Rat	Enhanced cellular delivery in arthritis and minimizes joint destruction	Rahman et al. (2015b)
PEG liposome, 90–100 nm	Prednisolone	Passive targeting	Rat AA	It provides long circulation and removes complete sign and symptom of RA within 2–5 days.	Rahman et al. (2015b)
Non-PEG liposomes, 100 nm	Prednisolone	Higher uptake by liver macrophages	Rat AA	Higher liver uptake makes shorter circulation and lesser accumulation in inflamed paw.	Rahman et al. (2015b)
PEG liposome 450–500 nm	Prednisolone	Enhanced uptake by liver macrophages	Rat AA	It got less therapeutic effect as compared to 100 nm PEG liposomes	Rahman et al. (2015b)
PHEA liposomes, 150 nm	PLP	Arthritic joint	Rat AA	It is biodegradable in nature and equally effective as like PLP loaded PEG liposome	Rahman et al. (2015b)
RGD-PEG liposome, 100 nm	DEX	αvβ3 and integrins	Lipopolysachharides (LPS)-induced inflammation and Rat AA	It received larger anti-arthritic effect by active targeting action in Rat AA	Rahman et al. (2015b)
LUV, 100 nm	Indomethacin	Inflamed joint	Inflamed paw edema and adjuvant arthritis in rat	It received larger anti-arthritic effects	Rahman et al. (2015b)
Lipogelosome, 235–242 nm	Diclofenac sodium	integrins	AIA in rabbits	It showed 90% inhibition in joint swelling	Rahman et al. (2015b)
Conventional liposomes, 100 nm	MTX	Inhibitory action on IL-1β and IL-6 mRNA expression	AIA in rabbits	It got 10 times more anti-arthritic efficacy as compared to free MTX.	Rahman et al. (2015b)
PEG liposome, 100 nm	MTX	Passive targeting	CIA in rat	Achieved longer circulation and enhanced anti-arthritic effect	Rahman et al. (2015b)
Conventional liposome, 100 nm	SOD	Targeting on ROS	Rat AA	It make shorter circulation time	Rahman et al. (2015b)
PEG liposomes, 100–110 nm	SOD	Achieved passive targeting and acting on ROS	AIA in wistar rat	It received 17 times higher uptake in the inflamed area with respect to large size SOD loaded liposome	Rahman et al. (2015b)
Cationic liposome, 2000–3000 nm	siRNA	Silence the IL-1, IL-6, and IL-18	AA in mice	It caused complete cure of arthritic mice	Rahman et al. (2015b)
Cationic liposome, 200 nm	Lf	Binding to iron in synovial tissue	Mouse CIA	It received greater reduction in severity of arthritic effect as compared to Lf only.	Rahman et al. (2015b)
Liposomes and their size	Loaded drugs	Targeting site	Disease	Outcomes	References
Anionic liposome, 420 nm	5-ASA and SOD	epithelial	Colitis (IBD), colitis-induced rats	It prolonged the residence time and enhanced the uptake in the intestinal inflamed mucosa and further these showed higher anti-inflammatory and antioxidant action than individual drug molecule	Jubeh et al. (2005), Kesisoglou et al. (2005)
Anionic liposome, 390 nm	4-amino tempol	Epithelial	Colitis (IBD), colitis-induced rats	It showed enhanced uptake by macrophages in intestinal mucosa to exerted significant anti-inflammatory effects as compared to solution	Jubeh et al. (2004)
Anionic liposome, 405 nm	Catalase	Epithelial	Colitis (IBD), colitis-induced rats	Enhanced uptake by macrophages in inflamed sites to produces more therapeutic effects and longer prolonged residence at inflamed loci	Jubeh et al. (2004)

MLV: Multilamellar vesicle; LUV: large unilamellars vesicles; AIA: adjuvant-induced arthritis; SUV: small unilamellars vesicle; PEG: polyethylene glycol; AA: adjuvant arthritis; DEX: dexamethasone; PHEA: poly (hydroxyethyl-l-asparagine; RGD: arginine-glycine-aspartic acid; RA: rheumatoid arthritis; PLP: prednisolone phosphate; MTX: methotrexate; SOD: superoxide dismutase; ROS: reactive oxygen species; siRNA: small interfering RNA; Lf: lactoferrin; IL: interleukins; CIA: collagen-induced arthritis; cAMP: cyclic adenosine monophosphate; VIP: vasoactive intestinal peptide; SLX: sialyl Lewis X; N/A; not available; 5-ASA: 5-aminosalicylic acid; IBD: inflammatory bowel disease; RGD: Arginine-glycine-aspartic acid; mAB: Monoclonal antibody; IC50: half maximal inhibitory concentration; DOX: doxorubicin.

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