Abstract
Background: After almost 30 years of study, it is a scientific fact that inflammation is the root cause of arthritis.
Objective: Guggul has a beneficial role in arthritis because of its ability to neutralize the NF-kappa factor. A topical drug delivery system is beneficial to overcome the problems associated with oral drug delivery and offers several potential advantages. Ultra-deformable vesicles (UDVs) are a special type of liposome made up of phospholipids and surfactants, and they are highly flexible.
Methods: In the present investigation, 20 formulations were suggested by Design Expert® 10 software (Central Composite Design) which were prepared using film hydration method with lecithin (70-90 mg), tween 80 (10–30 mg), Guggul extract (3 mg) and sonicated for 5–15 minutes. The formulation was optimized based on particle size (R₁) and maximum entrapment efficiency (R2).
Results: The optimized formulation consists of 78.92 mg soya phosphatidyl choline (lecithin), 22.08 mg Tween 80, and 3 mg Guggul with a sonication time of 12.74 minutes that resulted in a particle size of 375.5 ±15.1 nm and entrapment efficiency of 80.3 ± 3.1%. Guggul UDVs showed more antioxidant activity compared to Guggul extract, control and standard. Similar results were obtained in the case of anti-arthritic activity, which was measured by egg albumin denaturation, bovine serum albumin denaturation, proteinase inhibitory action, and anti-lipoxygenase activity. The data of both activities were analyzed using an unpaired t-test to determine significant values (p < 0.05).
Conclusion: These results demonstrate the potential of UDVs in the treatment of all arthritis diseases.
Graphical Abstract
[1]
Jin J, Sklar GE, Min Sen Oh V, Chuen Li S. Factors affecting therapeutic compliance: A review from the patient’s perspective. Ther Clin Risk Manag 2008; 4(1): 269-86.
[PMID: 18728716]
[PMID: 18728716]
[2]
de la Fuente-Herreruela D, Monnappa AK, Muñoz-Úbeda M, et al. Lipid–peptide bioconjugation through pyridyl disulfide reaction chemistry and its application in cell targeting and drug delivery. J Nanobiotechnology 2019; 17(1): 77.
[http://dx.doi.org/10.1186/s12951-019-0509-8] [PMID: 31226993]
[http://dx.doi.org/10.1186/s12951-019-0509-8] [PMID: 31226993]
[3]
Sarangi M, Padhi S. Novel herbal drug delivery system: An overview. Archives of Med Health Sci 2018; 6(1): 171-9.
[http://dx.doi.org/10.4103/amhs.amhs_88_17]
[http://dx.doi.org/10.4103/amhs.amhs_88_17]
[4]
Lombardo D, Kiselev MA, Caccamo MT. Smart nanoparticles for drug delivery application: development of versatile nanocarrier platforms in biotechnology and nanomedicine. J Nanomater 2019; 2019: 1-26.
[http://dx.doi.org/10.1155/2019/3702518]
[http://dx.doi.org/10.1155/2019/3702518]
[5]
Vinod KR, Kumar MS, Anbazhagan S, et al. Critical issues related to transfersomes - novel vesicular system. Acta Sci Pol Technol Aliment 2012; 11(1): 67-82.
[PMID: 22230977]
[PMID: 22230977]
[6]
Morilla MJ, Romero EL. Ultradeformable phospholipid vesicles as a drug delivery system: A review. Res. Reports in Transdermal Drug Deliv 2015; 4: 55-69.
[7]
Verma D, Verma S, Blume G, Fahr A. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm 2003; 258(1-2): 141-51.
[http://dx.doi.org/10.1016/S0378-5173(03)00183-2] [PMID: 12753761]
[http://dx.doi.org/10.1016/S0378-5173(03)00183-2] [PMID: 12753761]
[8]
Inde VV, Jangme CM, Chavan DV. A review on transferosome: Is a boon to human life. Int Res J Pharm Appl Sci 2013; 3(2): 174-9.
[9]
Ranade SY, Gaud RS. Current strategies in herbal drug delivery for arthritis: An overview. Int J Pharm Sci Res 2013; 4(10): 3782-94.
[10]
Reddy VJS, Rao GD, Lakshmi R. A review on anti-arthritic activity of some medicinal plants. J Glob Trends Pharm Sci 2014; 5(4): 2061-73.
[11]
Ahmad A, Abuzinadah MF, Alkreathy HM, Banaganapalli B, Mujeeb M. Ursolic acid rich Ocimum sanctum L leaf extract loaded nanostructured lipid carriers ameliorate adjuvant induced arthritis in rats by inhibition of COX-1, COX-2, TNF-α and IL-1: Pharmacological and docking studies. PLoS One 2018; 13(3): e0193451.
[http://dx.doi.org/10.1371/journal.pone.0193451] [PMID: 29558494]
[http://dx.doi.org/10.1371/journal.pone.0193451] [PMID: 29558494]
[12]
Siddiqui MZ. Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci 2011; 73(3): 255-61.
[PMID: 22457547]
[PMID: 22457547]
[13]
Shishodia S, Harikumar KB, Dass S, Ramawat KG, Aggarwal BB. The guggul for chronic diseases: ancient medicine, modern targets. Anticancer Res 2008; 28(6A): 3647-64.
[PMID: 19189646]
[PMID: 19189646]
[14]
Vyas K, Harisha CR, Vinay JS, Ruknuddin G, Prajapati P. Pharmacognostical and preliminary physicochemical profiles of Navaka Guggulu. Int J Health Allied Sci 2016; 5(2): 99-103.
[http://dx.doi.org/10.4103/2278-344X.180422]
[http://dx.doi.org/10.4103/2278-344X.180422]
[16]
Goyal C, Ahuja M, Sharma SK. Preparation and evaluation of anti-inflammatory activity of gugulipid-loaded proniosomal gel. Acta Pol Pharm 2011; 68(1): 147-50.
[PMID: 21485714]
[PMID: 21485714]
[17]
Kunnumakkara AB, Banik K, Bordoloi D, et al. Googling the Guggul (Commiphora and Boswellia) for prevention of chronic diseases. Front Pharmacol 2018; 9: 686.
[http://dx.doi.org/10.3389/fphar.2018.00686] [PMID: 30127736]
[http://dx.doi.org/10.3389/fphar.2018.00686] [PMID: 30127736]
[18]
Morsi NM, Aboelwafa AA, Dawoud MHS. Improved bioavailability of timolol maleate via transdermal transfersomal gel: Statistical optimization, characterization, and pharmacokinetic assessment. J Adv Res 2016; 7(5): 691-701.
[http://dx.doi.org/10.1016/j.jare.2016.07.003] [PMID: 27660724]
[http://dx.doi.org/10.1016/j.jare.2016.07.003] [PMID: 27660724]
[19]
Kharia AA, Singhai AK, Verma R. Formulation and evaluation of polymeric nanoparticles of an antiviral drug for gastroretention. Int J Pharma Sci Nanotechnol 2012; 4(4): 1557-62.
[http://dx.doi.org/10.37285/ijpsn.2011.4.4.6]
[http://dx.doi.org/10.37285/ijpsn.2011.4.4.6]
[20]
Mahmood S, Taher M, Mandal UK. Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application. Int J Nanomedicine 2014; 9: 4331-46.
[PMID: 25246789]
[PMID: 25246789]
[21]
Yalavarthi KS, Ivatury BTS, Raju MB. Formulation & evaluation of etoricoxib transferosomal gel. Eur J Biomed Pharm Sci 2018; 5(1): 512-24.
[22]
Tejaswini K, Swapna S, Babu AM, Bakshi V. Formulation and Evaluation of fluconazole loaded transfersome gel. Int J Sci Res Methodology Human 2016; 3(3): 1-14.
[23]
Mahmood S, Chatterjee B, Mandal UK. Nano transfersomes vesicles of raloxifene HCL with sorbitan 80: formulation and characterization. Bioequivalence & Bioavailability Int J 2018; 2(1): 1-7.
[24]
Duplessis J, Ramachandran C, Weiner N, Müller D. The influence of particle size of liposomes on the deposition of drug into skin. Int J Pharm 1994; 103(3): 277-82.
[http://dx.doi.org/10.1016/0378-5173(94)90178-3]
[http://dx.doi.org/10.1016/0378-5173(94)90178-3]
[25]
M VL. Zafaruddin M, Kuchana V. Design and characterization of transfersomal gel of repaglinide. Int Res J Pharm 2015; 6(1): 38-42.
[http://dx.doi.org/10.7897/2230-8407.0619]
[http://dx.doi.org/10.7897/2230-8407.0619]
[26]
Sharma G, Goyal H, Thakur K, Raza K, Katare OP. Novel elastic membrane vesicles (EMVs) and ethosomes-mediated effective topical delivery of aceclofenac: a new therapeutic approach for pain and inflammation. Drug Deliv 2016; 23(8): 3135-45.
[http://dx.doi.org/10.3109/10717544.2016.1155244] [PMID: 26960815]
[http://dx.doi.org/10.3109/10717544.2016.1155244] [PMID: 26960815]
[27]
Hussain A, Singh S, Sharma D, Webster T, Shafaat K, Faruk A. Elastic liposomes as novel carriers: recent advances in drug delivery. Int J Nanomedicine 2017; 12: 5087-108.
[http://dx.doi.org/10.2147/IJN.S138267] [PMID: 28761343]
[http://dx.doi.org/10.2147/IJN.S138267] [PMID: 28761343]
[28]
Kumar R, Rana AC, Bala R, Seth N. Formulation and evaluation of elastic liposomes of clotrimazole. Int J Drug Dev Res 2012; 4(3): 348-55.
[29]
Venkatesh DN, Kalyani K, Tulasi K, Priyanka VSP, Ali SKA, Kiran HC. Transfersomes: A novel technique for transdermal drug delivery. Int J Res Pharm Nanosci 2014; 3(4): 266-76.
[30]
Chanda S, Dave R. In vitro models for antioxidant activity evaluation and some medicinal plants possessing antioxidant properties: An overview. Afr J Microbiol Res 2009; 3(13): 981-96.
[31]
Bhakya S, Muthukrishnan S, Sukumaran M, Muthukumar M. Biogenic synthesis of silver nanoparticles and their antioxidant and antibacterial activity. Appl Nanosci 2016; 6(5): 755-66.
[http://dx.doi.org/10.1007/s13204-015-0473-z]
[http://dx.doi.org/10.1007/s13204-015-0473-z]
[32]
Boora F, Chirisa E, Mukanganyama S. Evaluation of nitrite radical scavenging properties of selected zimbabwean plant extracts and their phytoconstituents. J Food Processing 2014; pp. 1-7.
[33]
Parul R, Kundu SK, Saha P. In vitro nitric oxide scavenging activity of methanol extracts of three Bangladeshi medicinal plants. Pharma Innovation J 2013; 1(12): 83-8.
[34]
Patel A, Patel A, Patel A, Patel NM. Determination of polyphenols and free radical scavenging activity of Tephrosia purpurea linn leaves (Leguminosae). Pharmacognosy Res 2010; 2(3): 152-8.
[http://dx.doi.org/10.4103/0974-8490.65509] [PMID: 21808558]
[http://dx.doi.org/10.4103/0974-8490.65509] [PMID: 21808558]
[35]
Keser S, Celik S, Turkoglu S, Yilmaz O, Turkoglu I. Hydrogen peroxide radical scavenging and total antioxidant activity of hawthorn. Chem J 2012; 2(1): 9-12.
[36]
Bora KS, Sharma A. Evaluation of antioxidant and free-radical scavenging potential of Artemisia absinthium. Pharm Biol 2011; 49(12): 1216-23.
[http://dx.doi.org/10.3109/13880209.2011.578142] [PMID: 21999109]
[http://dx.doi.org/10.3109/13880209.2011.578142] [PMID: 21999109]
[37]
Chandra MS, Balamurugan V, Salini ST, Rekha R. Metal ion chelating activity and hydrogen peroxide scavenging activity of medicinal plant Kalanchoe pinnata. J Chem Pharm Res 2012; 4(1): 197-202.
[38]
Naithani V, Singhal AK, Chaudhary M. Comparative evaluation of metal chelating, antioxidant, and free radical scavenging activity of TROIS and six products commonly used to control pain and inflammation associated with arthritis. Int J Drug Dev Res 2011; 3(4): 208-16.
[39]
Wong FC, Yong AL, Ting EPS, Khoo SC, Ong HC, Chai TT. Antioxidant, metal chelating, anti-glucosidase activities and phytochemical analysis of selected tropical medicinal plants. Iran J Pharm Res 2014; 13(4): 1409-15.
[PMID: 25587331]
[PMID: 25587331]
[40]
Ghosh S, Saha K, Chandra S, Gupta D, Gomes A. In-vitro and in-vivo anti-arthritic and anti-inflammatory activity of Bungarus Fasciatus venom. J Toxins 2015; 2(1): 1-5.
[41]
Shunmugaperumal T, Kaur V. In vitro anti-inflammatory and antimicrobial activities of azithromycin loaded in chitosan- and tween 20-based oil-in-water macroemulsion for acne management. AAPS PharmSciTech 2016; 17(3): 700-9.
[http://dx.doi.org/10.1208/s12249-015-0401-2] [PMID: 26314246]
[http://dx.doi.org/10.1208/s12249-015-0401-2] [PMID: 26314246]
[42]
Godhandaraman S, Ramalingam V. In vitro anti-inflammatory activity of different parts of Pedalium murex (L.). Int J Herb Med 2016; 4(3): 31-6.
[43]
Ingale PL, Kasture VS. Evaluation of antioxidant and anti-arthritic activities of some 2-arylaminothiazole derivatives. Int J Pharm Pharm Sci 2014; 6(1): 547-9.
[44]
Phongpradist R, Chaiyana W, Anuchapreeda S. Curcumin-loaded multi-valent ligands conjugated-nanoparticles for anti-inflammatory activity. Int J Pharm Pharm Sci 2015; 7(4): 203-8.
[45]
Leelaprakash G, Dass SM. In vitro anti-inflammatory activity of methanol extract of Enicostemma axillare. Int J Drug Dev Res 2011; 3(3): 189-96.
[46]
Govendappa M, Sadananda TS, Channabasava R, Raghavendra VB. In-vitro anti-inflammatory, lipoxygenase, xanthine oxidase and acetylcholinesterase inhibitory activity of Tecoma Stans (L.) Juss. Ex Kunth. Int J Pharma Bio Sci 2011; 2(2): 276-85.
[47]
Sinbad O, Samuel F, Adewale A, Adedoyin O. Evaluation of membrane stabilizing, proteinase and lipoxygenase inhibitory activities of ethanol extract of root and stem of Sphenocentrum jollyanum Pierre. J Adv Biol Biotechnol 2017; 13(1): 1-8.
[http://dx.doi.org/10.9734/JABB/2017/34121]
[http://dx.doi.org/10.9734/JABB/2017/34121]
[48]
Alam F, Saqib QN, Ashraf M. Gaultheria trichophylla (Royle): a source of minerals and biologically active molecules, its antioxidant and anti-lipoxygenase activities. BMC Complement Altern Med 2017; 17(1): 3.
[http://dx.doi.org/10.1186/s12906-016-1511-4] [PMID: 28049535]
[http://dx.doi.org/10.1186/s12906-016-1511-4] [PMID: 28049535]
[49]
Paul S, Sasikumar CS, Dakshinamoorthi BM. In vitro studies of biosilver nanoparticles in cytotoxicity and anti-inflammatory. J Complement Med Alt Healthcare 2018; 7(4): 1-11.
[50]
Dhananjaya BL, Eshwarappa RSB, Ramachandra YL, Subaramaihha SR, Subbaiah SGP, Austin RS. Anti-lipoxygenase activity of leaf gall extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae). Pharmacognosy Res 2016; 8(1): 78-82.
[http://dx.doi.org/10.4103/0974-8490.171103] [PMID: 26941541]
[http://dx.doi.org/10.4103/0974-8490.171103] [PMID: 26941541]
