We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×

Thermoresponsive curcumin/DsiRNA nanoparticle gels for the treatment of diabetic wounds: synthesis and drug release

    Haliza Katas

    *Author for correspondence:

    E-mail Address: haliza.katas@ukm.edu.my

    Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    ,
    Chai Yi Wen

    Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    ,
    Muhammad Irfan Siddique

    Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    ,
    Zahid Hussain

    Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia

    &
    Fatin Hanini Mohd Fadhil

    Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Published Online:https://doi.org/10.4155/tde-2016-0075

    Aim: Chitosan (CS) has been extensively studied as drug delivery systems for wound healing. Results/methodology: CS nanoparticles were loaded with curcumin (Cur) and DsiRNA against prostaglandin transporter gene and they were incorporated into 20 and 25% w/v Pluronic F-127. The gels were later analyzed for their rheology, gelation temperature (Tgel), morphology, drug incorporation and in vitro drug release. The particle size was in the range of 231 ± 17–320 ± 20 nm, depending on CS concentration. The gels had Tgel of 23–28°C and exhibited sustained drug release with high accumulated amount of drugs over 48 h. Conclusion: A thermo-sensitive gel containing Cur/DsiRNA CS nanoparticles was successfully developed and has a great potential to be further developed.

    References

    • 1 Lipsky BA. Evidence-based antibiotic therapy of diabetic foot infections. FEMS Immunol. Med. Microbiol. 26(3–4), 267–276 (1999).
    • 2 Pecoraro RE, Reiber GE. Pathways to diabetic limb amputation: basis for prevention. Diabetes Care. 13(5), 513–521 (1990).
    • 3 Falanga V. Wound healing and its impairment in the diabetic foot. The Lancet 366(9498), 1736–1743 (2005).
    • 4 Galiano RD, Tepper OM, Pelo CR et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am. J. Pathol. 164(6), 1935–1947 (2004).
    • 5 Galkowska H, Wojewodzka U, Olszewski WL. Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair Regen. 14(5), 558–565 (2006).
    • 6 Gibran NS, Jang Y-C, Isik FF et al. Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. J. Surg. Res. 108(1), 122–128 (2002).
    • 7 Goren I, Müller E, Pfeilschifter J et al. Severely impaired insulin signaling in chronic wounds of diabetic Ob/Ob mice: a potential role of tumor necrosis factor-A. Am. J. Pathol. 168(3), 765–777 (2006).
    • 8 Lobmann R, Ambrosch A, Schultz G et al. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia 45(7), 1011–1016 (2002).
    • 9 Maruyama K, Asai J, Ii M et al. Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. Am. J. Pathol. 170(4), 1178–1191 (2007).
    • 10 Guo SA, Dipietro LA. Factors affecting wound healing. J. Dent. Res. 89(3), 219–229 (2010).
    • 11 Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int. J. Vasc. Med. 2012, 1–30 (2012).
    • 12 Lipsky BA, Berendt AR, Cornia PB et al. Infectious diseases society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin. Infect. Dis. 54(2012), e132–e173.
    • 13 Dewick PM. Medicinal Natural Products: A Biosynthetic Approach (Second Ed.). John Wiley & Sons, London, UK (2002).
    • 14 Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 23(1A), 363–398 (2003).
    • 15 Sharma R, Gescher A, Steward W. Curcumin: the story so far. Eur. J. Cancer 41(13), 1955–1968 (2005).
    • 16 Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann. NY Acad. Sci. 1056, 206–217 (2005).
    • 17 Prausnitz MR, Langer R. Transdermal drug delivery. Nat. Biotechnol. 26(11), 1261–1268 (2008).
    • 18 Zhang Z, Tsai PC, Ramezanli T, Michniak-Kohn BB. Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 5(3), 205–218 (2013).
    • 19 Raja MAG, Katas H, Hamid ZA, Razali NA. Physicochemical properties and in vitro cytotoxicity studies of chitosan as a potential carrier for dicer-substrate siRNA. J. Nanomater. 2013, 1–10 (2013).
    • 20 Kim S-K, Rajapakse N. Enzymatic production and biological activities of chitosan oligosaccharides (COS): a review. Carbohydr. Polym. 62(4), 357–368 (2005).
    • 21 Kim D-H, Behlke MA, Rose SD, Chang M-S, Choi S, Rossi JJ. Synthetic DsiRNA dicer substrates enhance RNAi potency and efficacy. Nat. Biotechnol. 23(2), 222–226 (2005).
    • 22 Yeon S, Chul J, Moo Y. Poly(ethylene oxide)-poly(ethylene oxide)/ply(∈-caprolactone) (PCL) amphiphilic block copolymeric nanospheres: thermo-responsive drug release behaviors. J. Control. Rel. 65(3), 345–358 (2000).
    • 23 Jørgensen EB, Hvidt S, Brown W, Schillen K. Effects of salts on the micellization and gelation of a triblock copolymer studied by rheology and light scattering. Macromolecules 30(8), 2355–2364 (1997).
    • 24 Escobar-Chávez J, López-Cervantes M, Naik A, Kalia Y, Quintanar-Guerrero D, Ganem-Quintanar A. Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations. J. Pharm. Pharm. Sci. 9(3), 339–358 (2006).
    • 25 Chuah LH, Billa N, Roberts CJ, Burley JC, Manickam S. Curcumin-containing chitosan nanoparticles as a potential mucoadhesive delivery system to the colon. Pharm. Dev. Technol. 18(3), 591–599 (2013).
    • 26 Liu L, Zhou C, Xia X, Liu Y. Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation. Int. J. Nanomedicine 11, 761–769 (2016).
    • 27 Mohanraj V, Chen Y. Nanoparticles: a review. Trop. J. Pharm. Res. 5(1), 561–573 (2007).
    • 28 Gan Q, Wang T, Cochrane C, Mccarron P. Modulation of surface charge, particle size and morphological properties of chitosan–TPP nanoparticles intended for gene delivery. Colloids Surf. B. Biointerfaces. 44(2–3), 65–73 (2005).
    • 29 Shu X, Zhu K. The influence of multivalent phosphate structure on the properties of ionically cross-linked chitosan films for controlled drug release. Eur. J. Pharm. Biopharm. 54(2), 235–243 (2002).
    • 30 Chen Y, Mohanraj VJ, Parkin JE. Chitosan-dextran sulfate nanoparticles for delivery of an anti-angiogenesis, Peptide. Lett. Pept. Sci. 10(5), 621–629 (2003).
    • 31 Gan Q, Wang T. Chitosan nanoparticle as protein delivery carrier – systematic examination of fabrication conditions for efficient loading and release. Colloids Surf. B. Biointerfaces 59(1), 24–34 (2007).
    • 32 Couvreur P, Barratt G, Fattal E, Legrand P, Vauthier C. Nanocapsule technology: a review. Crit. Rev. Ther. Drug Carrier Syst. 19(2), 99–134 (2002).
    • 33 Modaresi SMS, Ejtemaei Mehr S, Faramarzi MA, Esmaeilzadeh Gharehdaghi E, Azarnia M, Modarressi MH et al. Preparation and characterization of self-assembled chitosan nanoparticles for the sustained delivery of streptokinase: an in vivo study. Pharm. Dev. Technol. 19(5), 593–597 (2014).
    • 34 Li X, Deng X, Yuan M, Xiong C, Huang Z, Zhang Y et al. Investigation on process parameters involved in preparation of poly-DL-lactide-poly (ethylene glycol) microspheres containing Leptospira interrogans antigens. Int. J. Pharm. 178(2), 245–255 (1999).
    • 35 Mehta RC, Thanoo B, Deluca PP. Peptide containing microspheres from low molecular weight and hydrophilic poly (D, L-lactide-co-glycolide). J. Control. Rel. 41, 249–257 (1996).
    • 36 Rafati H, Coombes A, Adler J, Holland J, Davis S. Protein-loaded poly (DL-lactide-co-glycolide) microparticles for oral administration: formulation, structural and release characteristics. J. Control. Rel. 43(1), 89–102 (1997).
    • 37 Maurya SD, Aggarwal S, Kumar G, Tilak VK. Design and evaluation of SRM microspheres of metformin hydrochloride. Pharmacie Globale. 1(6), 1–5 (2010).
    • 38 Gref R, Domb A, Quellec P et al. The controlled intravenous delivery of drugs using peg-coated sterically stabilized nanospheres. Adv. Drug Deliv. Rev. 64, 316–326 (2012).
    • 39 Katas H, Alpar HO. Development and characterisation of chitosan nanoparticles for siRNA delivery. J. Control. Release 115(2), 216–225 (2006).
    • 40 Hasanovic A, Zehl M, Reznicek G, Valenta C. Chitosan tripolyphosphate nanoparticles as a possible skin drug delivery system for aciclovir with enhanced stability. J. Pharm. Pharmacol. 61(12), 1609–1616 (2009).
    • 41 Holzerny P, Ajdini B, Heusermann W et al. Biophysical properties of chitosan/siRNA polyplexes: profiling the polymer/siRNA interactions and bioactivity. J. Control. Release 157(2), 297–304 (2012).
    • 42 Csaba N, Köping-Höggård M, Alonso MJ. Ionically crosslinked chitosan/tripolyphosphate nanoparticles for oligonucleotide and plasmid DNA delivery. Int. J. Pharm. 382(1–2), 205–214 (2009).
    • 43 Martin ME, Rice KG. Peptide-guided gene delivery. AAPS J. 9(1), E18–E29 (2007).
    • 44 Baloglu E, Karavana SY, Senyigit ZA, Guneri T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm. Dev. Technol. 16(6), 627–636 (2011).
    • 45 Cabana A, Aıt-Kadi A, Juhász J. Study of the gelation process of polyethylene oxide a-polypropylene oxide b-polyethylene oxide a copolymer (poloxamer 407) aqueous solutions. J. Colloid Interface Sci. 190(2), 307–312 (1997).
    • 46 Jain NJ, Aswal V, Goyal P, Bahadur P. Micellar structure of an ethylene oxide-propylene oxide block copolymer: a small-angle neutron scattering study. J. Phys. Chem. B 102(43), 8452–8458 (1998).
    • 47 Bentley MVL, Marchetti JM, Ricardo N, Ali-Abi Z, Collett JH. Influence of lecithin on some physical chemical properties of poloxamer gels: rheological, microscopic and in vitro permeation studies. Int. J. Pharm. 193(1), 49–55 (1999).
    • 48 Galgatte UC, Chaudhari PD. Preformulation study of poloxamer 407 gels: effect of additives. J. Pharm. Pharm. Sci. 6(1), 130–133 (2014).
    • 49 Li XY, Zhu ZJ, Cheng AY. Characteristics of poloxamer thermosensitive in situ gel of dexamethasone sodium phosphate. Yao Xue Xue Bao 43(2), 208–213 (2008).
    • 50 Kim E-Y, Gao Z-G, Park J-S, Li H, Han K. rhEGF/HP-β-CD complex in poloxamer gel for ophthalmic delivery. Int. J. Pharm. 233(1–2), 159–167 (2002).
    • 51 Ryu J-M, Chung S-J, Lee M-H, Kim C-K, Shim C-K. Increased bioavailability of propranolol in rats by retaining thermally gelling liquid suppositories in the rectum. J. Control. Rel. 59(2), 163–172 (1999).
    • 52 Miller SC, Drabik BR. Rheological properties of poloxamer vehicles. Int. J. Pharm. 18(3), 269–276 (1984).
    • 53 Gong C, Qi T, Wei X et al. Thermosensitive polymeric hydrogels as drug delivery systems. Curr. Med. Chem. 20(1), 79–94 (2013).
    • 54 Meenakshi P, Hetal T, Kasture P. Preparation and evaluation of thermoreversible formulations of flunarizine hydrochloride for nasal delivery. Int. J. Pharm. Pharm. Sci. 2(4), 115–120 (2010).
    • 55 Choi H-G, Jung J-H, Ryu J-M, Yoon S-J, Oh Y-K, Kim C-K. Development of in situ-gelling and mucoadhesive acetaminophen liquid suppository. Int. J. Pharm. 165(1), 33–44 (1998).
    • 56 Edsman K, Carlfors J, Petersson R. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. Eur. J. Pharm. Sci. 6(2), 105–112 (1998).
    • 57 Kar F, Arslan N. Effect of temperature and concentration on viscosity of orange peel pectin solutions and intrinsic viscosity–molecular weight relationship. Carbohydr. Polym. 40(4), 277–284 (1999).
    • 58 Wu T, Zivanovic S, Draughon FA, Conway WS, Sams CE. Physicochemical properties and bioactivity of fungal chitin and chitosan. J. Agric. Food Chem. 53(10), 3888–3894 (2005).
    • 59 Jia-Hui Y, Yu-Min D, Hua Z. Blend films of chitosan–gelatin. Wuhan Univ. J. Nat. Sci. 4(4), 476–476 (1999).
    • 60 Mohanty C, Sahoo SK. The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials 31(25), 6597–6611 (2010).
    • 61 Zhang W, Shi Y, Chen Y, Hao J, Sha X, Fang X. The potential of pluronic polymeric micelles encapsulated with paclitaxel for the treatment of melanoma using subcutaneous and pulmonary metastatic mice models. Biomaterials 32(25), 5934–5944 (2011).
    • 62 Gilbert JC, Hadgraft J, Bye A, Brookes LG. Drug release from Pluronic F-127 gels. Int. J. Pharm. 32(2–3), 223–228 (1986).
    • 63 Ibrahim E-S, Ismail S, Fetih G, Shaaban O, Hassanein K, Abdellah N. Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application. Acta Pharm. 62(1), 59–70 (2012).
    • 64 Brodin B, Steffansen B, Nielsen CU. Passive diffusion of drug substances: the concepts of flux and permeability. In: Molecular Biopharmaceutics: aspects of Drug Characterisation, Drug Delivery and Dosage Form Evaluation. Steffeansen B, Brodin B, Nielson CU (Eds). Pharmaceutical Press, London, UK, 135–151 (2010).