Formulation and evaluation of piperacillin tazobactam loaded aquasomal gel for the treatment of noma
DOI:
https://doi.org/10.69857/joapr.v14i3.1969Keywords:
Piperacillin, Tazobactam, Noma, Aquasomes, Central Composite DesignAbstract
Background: Noma is a rapidly progressing gangrenous disease that affects the oral and facial tissues, mainly in malnourished and immunocompromised children. Delayed intervention often results in severe tissue destruction, facial deformity, and high morbidity. Although broad-spectrum antibiotics are routinely employed, conventional dosage forms often fail to achieve sufficient drug concentrations at the site of infection. Poor local absorption, limited tissue penetration, and the need for repeated administration reduce therapeutic effectiveness and patient compliance. Hence, a novel topical drug delivery system is required to enhance local drug delivery and clinical outcomes. This manuscript aims to formulate and evaluate a Piperacillin–Tazobactam-loaded Aquasomal gel for topical treatment of Noma. Methodology: Aquasomes composed of a calcium phosphate core coated with trehalose were prepared by the sonication method for topical delivery of Piperacillin–Tazobactam. A Central Composite Design (CCD) using Design-Expert® software was used to optimize formulation variables to improve entrapment efficiency and control drug release. The optimized Aquasomes were evaluated for particle size, polydispersity index, zeta potential, and drug entrapment efficiency, and then incorporated into a 1% Carbopol gel. Results & Discussion: The optimized formulation exhibited a particle size of 186 nm, a zeta potential of –19.37 mV, an entrapment efficiency of 68.18%, and sustained drug release of 61.1%. The gel exhibited suitable physicochemical properties and strong antibacterial activity against methicillin-resistant Staphylococcus aureus. Conclusion: The developed Aquasomal gel represents a promising topical therapy for the effective management of Noma.
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References
Marck KW. Cancrum oris and noma: some etymological and historical remarks. Br J Plast Surg, 56(6), 524–527 (2003) https://doi.org/10.1016/S0007-1226(03)00224-8
Maguire BJ, Shrestha P, Rashan S, Shrestha R, Harriss E, Varenne B, Guérin PJ. Protocol for a systematic review of the evidence-based knowledge on the distribution, associated risk factors, the prevention and treatment modalities for noma. Wellcome Open Res, 8, 125 (2023) https://doi.org/10.35802/222410
Galli A, Brugger C, Fürst T, Monnier N, Winkler MS, Steinmann P. Prevalence, incidence, and reported global distribution of noma: a systematic literature review. Lancet Infect Dis, 22(8), e221–e230 (2022) https://doi.org/10.1016/S1473-3099(21)00698-8
Srour ML, Marck K, Baratti-Mayer D. Noma: overview of a neglected disease and human rights violation. Am J Trop Med Hyg, 96(2), 268–274 (2017) https://doi.org/10.4269/ajtmh.16-0718
Lee YJ, Kang G, Zang DY, Lee DH. Population pharmacokinetic modeling of piperacillin/tazobactam in healthy adults and exploration of optimal dosing strategies. Pharmaceuticals, 18(8), 1124 (2025) https://doi.org/10.3390/ph18081124
Hayashi Y, Roberts JA, Paterson DL, Lipman J. Pharmacokinetic evaluation of piperacillin-tazobactam. Expert Opin Drug Metab Toxicol, 6(8), 1017–1031 (2010) https://doi.org/10.1517/17425255.2010.506187
Ayom GE, Malima NM, Owonubi SJ, Revaprasadu N. Aquasomes: a novel nanocarrier system for drug delivery. In: Advanced Nanoformulations. Academic Press, 289–309 (2023) https://doi.org/10.1016/B978-0-323-85785-7.00018-8
Umashankar MS, Sachdeva RK, Gulati M. Aquasomes: a promising carrier for peptides and protein delivery. Nanomedicine, 6(3), 419–426 (2010) https://doi.org/10.1016/j.nano.2009.11.002
Banerjee S, Sen KK. Aquasomes: a novel nanoparticulate drug carrier. J Drug Deliv Sci Technol, 43, 446–452 (2018) https://doi.org/10.1016/j.jddst.2017.11.011
Sahu V, Sahoo SK, Sahoo AC. Aquasome: as drug delivery carrier in the pharmaceutical field. Indian J Pharm Educ Res, 58(3 Suppl), s757–s767 (2024) https://doi.org/10.5530/ijper.58.3s.77
Shanmugam B, Srinivasan UM. Formulation and characterization of antibiotic drug loaded aquasome for the topical application. Future Sci OA, 10(1), FSO949 (2024) https://doi.org/10.1080/20565623.2024.2367849
Ojewumi ME, Ehinmowo AB, Ekanem GP, Nsionu JU, Bolujo EO. Central composite design for solvent extraction of oil from neem (Azadirachta indica) seed. IOP Conf Ser Mater Sci Eng, 1107(1), 012109 (2021) https://doi.org/10.1088/1757-899X/1107/1/012109
Alhamdany AT, Saeed AM, Alaayedi M. Nanoemulsion and solid nanoemulsion for improving oral delivery of a breast cancer drug: formulation, evaluation, and a comparison study. Saudi Pharm J, 29(11), 1278–1288 (2021) https://doi.org/10.1016/j.jsps.2021.09.016
Wang YW, Jou CH, Yang MC. Effect of quaternized chitosan on the fusion efficiency and cytocompatibility of liposomes. J Polym Res, 19(1), 9755 (2012) https://doi.org/10.1007/s10965-011-9755-7
Karthik S, Raghavan CV, Marslin G, Rahman H, Selvaraj D, Balakumar K, Franklin G. Quillaja saponin: a prospective emulsifier for the preparation of solid lipid nanoparticles. Colloids Surf B Biointerfaces, 147, 274–280 (2016) https://doi.org/10.1016/j.colsurfb.2016.07.065
Farooq M, Usman F, Zaib S, Shah HS, Jamil QA, Akbar Sheikh F, Khan A, Rabea S, Hagras SA, El-Saber Batiha G, Khan I. Fabrication and evaluation of voriconazole loaded transethosomal gel for enhanced antifungal and antileishmanial activity. Molecules, 27(10), 3347 (2022) https://doi.org/10.3390/molecules27103347
Das S, Bishal A, Debnath B, Mukherjee S. Advancements in aquasomes-based topical drug delivery for enhanced dermatological treatments. Dermatol Rev, 6(1), e70014 (2025) https://doi.org/10.1002/der2.70014
Mourtas S, Fotopoulou S, Duraj S, Sfika V, Tsakiroglou C, Antimisiaris SG. Liposomal drugs dispersed in hydrogels: effect of liposome, drug and gel properties on drug release kinetics. Colloids Surf B Biointerfaces, 55(2), 212–221 (2007) https://doi.org/10.1016/j.colsurfb.2006.12.005
Aggarwal G, Nagpal M, Kaur G. Development and comparison of nanosponge and niosome based gel for the topical delivery of tazarotene. Pharm Nanotechnol, 4(3), 213–228 (2016) https://doi.org/10.2174/2211738504666160804154213
Shirsand SB, Para MS, Nagendrakumar D, Kanani KM, Keerthy D. Formulation and evaluation of ketoconazole niosomal gel drug delivery system. Int J Pharm Investig, 2(4), 201–207 (2012) https://doi.org/10.4103/2230-973X.107002
Harun SN, Nordin SA, Gani SS, Shamsuddin AF, Basri M, Basri HB. Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics. Int J Nanomedicine, 13, 2571–2584 (2018) https://doi.org/10.2147/IJN.S151788
Elangovan S, Arumugam S. Purification, characterization, and biological activities of melanin pigment isolated from Indian squid Uroteuthis duvaucelii. Aquac Int, 31(6), 3095–3108 (2023) https://doi.org/10.1007/s10499-023-01158-9
Miller DP, de Pablo JJ, Corti H. Thermophysical properties of trehalose and its concentrated aqueous solutions. Pharm Res, 14(5), 578–590 (1997) https://doi.org/10.1023/A:1012192725996
Gupta AK, Gupta D, Gupta V. Aquasomes: a self-assembled nano-particulate carrier system. Int J Curr Res Rev, 13(4), 44–52 (2021) https://doi.org/10.31782/IJCRR.2021.13427
Bwalya F, Barre L, Erdem M, Kaynak MS. Preparation and characterization of vitamin C aquasomes. Recent Adv Drug Deliv Formul, 19(3), 290–302 (2025) https://doi.org/10.2174/0126673878352032250325002719
Sayed S, Abdel-Moteleb M, Amin MM, Khowessah OM. Cubogel as potential platform for glaucoma management. Drug Deliv, 28(1), 293–305 (2021) https://doi.org/10.1080/10717544.2021.1872740
Teo MZ, Loo HL, Goh BH, Chuah LH. Progress in topical nanoformulations against bacterial skin and soft tissue infections—current trends. Drug Deliv Transl Res, 15(11), 4141–4186 (2025) https://doi.org/10.1007/s13346-025-01924-7
Kulkarni S, Prabhakar B, Shende P. Nanodiamond-based berberine aquasomes for enhancing penetration across epidermis to treat psoriasis. Int J Pharm, 656, 124051 (2024) https://doi.org/10.1016/j.ijpharm.2024.124051
İlhan M, Gültekin HE, Rençber S, Şenyiğit Z, Aydın HH. Aquasomes: a novel platform for drug delivery. In: Systems of Nanovesicular Drug Delivery. Academic Press, 191–206 (2022) https://doi.org/10.1016/B978-0-323-91864-0.00020-6
Chrisikou I, Orkoula M, Kontoyannis C. FT-IR/ATR solid film formation: qualitative and quantitative analysis of a piperacillin-tazobactam formulation. Molecules, 25(24), 6051 (2020) https://doi.org/10.3390/molecules25246051
Toral M, Nova-Ramirez F, Nacaratte F. Simultaneous determination of piperacillin and tazobactam in the pharmaceutical formulation Tazonam® by derivative spectrophotometry. J Chil Chem Soc, 57(2), 1189–1193 (2012) https://doi.org/10.4067/S0717-97072012000200028
Zakir F, Vaidya B, Goyal AK, Malik B, Vyas SP. Development and characterization of oleic acid vesicles for the topical delivery of fluconazole. Drug Deliv, 17(4), 238–248 (2010) https://doi.org/10.3109/10717541003680981
Ahmed MM, Fatima F, Anwer MK, Ibnouf EO, Kalam MA, Alshamsan A, Aldawsari MF, Alalaiwe A, Ansari MJ. Formulation and in vitro evaluation of topical nanosponge-based gel containing butenafine for the treatment of fungal skin infection. Saudi Pharm J, 29(5), 467–477 (2021) https://doi.org/10.1016/j.jsps.2021.04.010
Sakran W, Abdel-Rashid RS, Saleh F, Abdel-Monem R. Ethosomal gel for rectal delivery of domperidone. Drug Deliv, 29(1), 1477–1491 (2022) https://doi.org/10.1080/10717544.2022.2072542
Budhiraja A, Dhingra G. Development and characterization of a novel antiacne niosomal gel of rosmarinic acid. Drug Deliv, 22(6), 723–730 (2015) https://doi.org/10.3109/10717544.2014.903010
Damera DP, Kaja S, Janardhanam LS, Alim S, Venuganti VV, Nag A. Synthesis, detailed characterization, and dual drug delivery application of BSA loaded aquasomes. ACS Appl Bio Mater, 2(10), 4471–4484 (2019) https://doi.org/10.1021/acsabm.9b00635
Shanmugam B, Srinivasan UM. Aquasomes nanoformulation for controlled release of drug and improved effectiveness against bacterial infections. Ther Deliv, 15(2), 95–107 (2024) https://doi.org/10.4155/tde-2023-0096
Waghule T, Rapalli VK, Singhvi G, Gorantla S, Khosa A, Dubey SK, Saha RN. Design of temozolomide-loaded proliposomes and lipid crystal nanoparticles with industrial feasible approaches: comparative assessment of drug loading, entrapment efficiency, and stability at plasma pH. J Liposome Res, 31(2), 158–168 (2021) https://doi.org/10.1080/08982104.2020.1748648
Vengala P, Dintakurthi S, Subrahmanyam CV. Lactose coated ceramic nanoparticles for oral drug delivery. J Pharm Res, 7(6), 540–545 (2013) https://doi.org/10.1016/j.jopr.2013.06.015
Patel MK, Shah S, Dubey BK, Basedia DK, Jain PK. Formulation and characterization of curcumin-loaded aquasomes for topical fungal treatment. Asian J Pharm Res Dev, 13(1), 10–14 (2025) https://doi.org/10.22270/ajprd.v13i1.1496
Bryson HM, Brogden RN. Piperacillin/tazobactam: a review of its antibacterial activity, pharmacokinetic properties and therapeutic potential. Drugs, 47(3), 506–535 (1994) https://doi.org/10.2165/00003495-199447030-00008
Lee JI, Kim KS, Oh BC, Kim NA, Kim IH, Park CG, Kim SJ. Acute necrotic stomatitis (noma) associated with methicillin-resistant Staphylococcus aureus infection in a newly acquired rhesus macaque (Macaca mulatta). J Med Primatol, 40(3), 188–193 (2011) https://doi.org/10.1111/j.1600-0684.2011.00470.x
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