Stimuli-sensitive Systems-an emerging delivery system for drugs

Figures & data

Table I. Various stimuli sensitive drug delivery systems.

Aim	Objective	Pharmaceutical uses	References
A work on environmentally responsive peptides as anticancer drug carriers had been carried out.	This study involved the development of environmentally responsive delivery systems by use of tumor pathology to trigger release of therapeutic agents at the target site.	Potential application includes the use of such technology for treatment of tumors with the help of signals.	Aluri et al. (2009)
A work on novel environmentally responsive ophthalmic drug delivery system had been carried out.	The objective of present study was to develop a temperature-triggered and ion-activated environmentally responsive system using ofloxacin as drug candidate.	In present study, temperature-triggered and ion-activated environmentally responsive systems were prepared for ocular drug delivery by using poloxamer-407 and sodium alginate.	Deshmukh and Fursule (2010)
Another work on temperature-responsive drug delivery system in conjunction with thermotherapy has been carried out.	–	These thermosensitive polymers are useful for the preparation of temperature-sensitive dendrimers.	Kojima (2010)
A work on the highly temperature-sensitive liposomes based on a thermosensitive block copolymer for tumor-specific chemotherapy has been done.	Incorporation of poly [2-(2-ethoxy)ethoxyethyl vinyl ether (EOEOVE)], which exhibits a lower critical solution temperature (LCST) around 40°C, provides temperature-sensitive properties for stable liposomes.	Liposome release can be controlled by adjusting a LCST of thermosensitive polymers at desired temperatures.	Strehl et al. (2013)
A work on redox-responsive polyplexes represent a promising class of nonviral gene delivery vectors.	Polyplexes were investigated as promising delivery vectors for a variety of nucleic acid therapeutics.	Polyplexes capable of responding to environmental changes by altering their properties and their behavior seemed to promise a significant improvement in delivery efficacy.	Manickam et al. (2010)
A preparation of thermo-responsive polymer membranes has been carried out.	The purpose of this study was to develop thermo-responsive membranes by using liquid crystals (LC) for controlled drug delivery system.	Thermo-responsive system found to be useful tool for drug delivery system which responds to the change of body temperature and/or the external thermal stimuli.	Sortino (2008)

Figure 1. Different levels of pH in the various parts of body.

Table II. pH in various cellular and tissue compartments under normal conditions.

Cellular/Tissue compartment	pH
Blood	7.35–7.45
Duodenum	7.0–8.5
Colon	7.0–7.5
Stomach	2.0–3.0
Early endosome	6.0–6.5
Late endosome	5.0–6.0
Golgi	6.4
Lysosome	4.5–5.0
Tumors, extracellular	7.2–6.5

Table III. Various colloidal carrier systems along with their therapeutic applications.

Carrier Type	Polymer/lipid	Drug/Gene	Therapeutic use	References
Liposome	Liposomes attached with a saccharide (lecithin) vector PEGylated liposome Copolymer of N-isopropylacryl amide and acryloylpyrrolidine (sterically stabilized liposome) Histidine-modified galactosylated cholesterol derivative—cationic liposome Anionic liposomes containing phosphatidylethanolamine (PE)	Sarcolysine Doxorubicin Hexadecyl phosphocholine Plasmid DNA Antisense oligonucleotids	Increased level of vectored liposome binding to malignant cells by 50–80% compared to liposome without vector Treatment of breast cancer due to higher efficacy and favorable safety profile Improved antitumor activity in breast carcinoma in nude mice Increased gene transfection to hepatocytes Effective in the treatment of viral infections cancer or inflammatory diseases	Vodovozova et al. (1998) Ganta et al. (2008) Arndt et al. (1997) Shigeta et al. (2007)
Niosomes	Amphiphilic co-polymer of poly (methoxy-polyethylene glycol cyanoacrylate-c0-n-hexadecyl cyano acrylate) (PEG-PH DCA) Polyethylene Poly (phthaloyl-L-lysine)	Hydroxy Camptothecin (HCPT) Doxorubicin Cisplatin	Antitumor activity, good tumor inhibition rate Helpful for the treatment of hepatic neoplasms Release the drug in a controlled fashion and also improve stability of vesicles both in vitro and in vivo.	Li and Wallace (2008) Li and Wallace (2008)
Dendrimers	Polyamidoamine dendrimer Drug linked to polyamidoamine dendrimer via pH-sensitive linker	Chlorambucil Doxorubicin	Drug was released in a pH-dependant fashion Improved cytotoxicity on Ca9-22 cells	Hui et al. (2005) Lai et al. (2007)
Nanoparticles/ Nanocapsules	Poly (alkylcyanoacrylate) nanoparticles with anticancer agents Poly (methylmethacrylate) nanoparticles with proteins and therapeutic agents Poly (alkylcyanoacrylate) Polyester nanoparticles with anti-parasitic/ antiviral agents Albumin, Chitosan, Dextran	Oligonucleotides Vaccine adjuvant Antiviral drugs Hydrophilic and protein affinity	Targeting, reduced toxicity, enhanced uptake of antitumor agents Enhanced bioavailability, protection from gastrointestinal enzymes Target reticuloendothelial systems for intracellular infections Targeted, improved and controlled delivery of drug	Vyas and Khar (2002) Vyas and Khar (2002) Vyas and Khar (2002) Vyas and Khar (2002)
Polymeric	Poly (N-isopropylacrylamide- cobutylmethacrylate-co-acrylic acid) Poly (N-isopropylacrylamide)	Insulin Doxorubicin	This system has a potential as a polypeptide drug carrier Showed improved anticancer activity in murine tumor models	Yong-Hee et al. (1994) Dufresne et al. (2004)

Table IV. Various temperature sensitive drug delivery systems.

Polymer	Therapeutic use	Drug/Gene	References
N-isopropylacrylamide and N, N-dimethylaminoethyl methacrylate (PNIPAm-co-PDMAEMA)	Improved gene delivery and effective gene transfection	pDNA	Hinrichs and Suhuurmans (1999)
Linear PNI-Pam-co-DMAEMA polymer	Improved efficacy of transfection		Alexander (2006)
PEI-PNIPAm polymer with 46-kDa PNIPAm grafts	More effective transfection efficacy		Alexander (2006)
Poly[2-(2-ethoxy) ethoxy ethylvinyl ether (EOEOVE)	Provide temperature-sensitive properties to stable liposomes (tumor-specific chemotherapy)	Doxorubicin	Kono et al. (2010)
Multiblock copolymers synthesized from pluronic and di-(ethylene glycol) divinyl ether	Used as delivery vehicle for controlled and sustained release of plasmid DNA	Plasmid DNA	Namgung et al. (2009)
Polyethylenimine (BPEI)/pDNA complex	Improved transfection efficacy	Plasmid DNA	Namgung et al. (2009)
Co-polymerization of PVP and acrylic acid	Provide sustained release of drug, also provide temperature-dependent release of FITC-dextran	Fluorescein isothiocyanate-dextran (FITC-dextran)	Sahoo et al. (1998)
Pluronic-g-PAA copolymers	In situ gelling vehicle for ophthalmic drug delivery, prolong the precorneal resident time, and improve ocular drug bioavailability	(Model Drug)	Ma et al. (2008)

Figure 2. The active drug targeting with surface-modified micelles.

Table V. Various ion-sensitive drug delivery systems.

Objective	Polymer	Drug	Therapeutic used	References
Formulation and evaluation of ion activated ocular gels of ketorolac Tromethamine	Gelrite	Ketorolac tromethamine	Improve the precorneal residence time and sustain the drug release	Vodithala et al. (2010)
Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin	Alginate/HPmC	Gatifloxacin	Produced sustained drug release over an 8-h period.	Liu et al. (2006)
Sustained ophthalmic delivery of ofloxacin From an ion-activated in situ gelling system	Sod Alginate/HPC	Ofloxacin	Sustained the drug release over a period of 8 hours.	Abraham et al. (2009)
Ion-activated in situ gelling systems for sustained ophthalmic delivery of ciprofloxacin hydrochloride	Gelrite gellan gum + sod alginate	Ciprofloxacin HCL	Sustained the drug release over a period of 8 hours.	Balasubramaniam et al. (2003)
Enhancement of miotic potential of pilocarpine by tamarind gum based in situ gelling ocular dosage form	Tamarind	Pilocarpine	Enhancement of miotic potential of pilocarpine	Mishra and Gilhotra (2008)
Sustained ophthalmic delivery of Levofloxacin Hemihydrate from an Ion-activated in situ gelling system	Gelrite	Levofloxacin Hemihydrate	Sustained the drug release over a period of 8 hours.	Kavitha and Rajas (2011)

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