A Review on Nanocarrier-based Polyherbal Drug Delivery Systems for
Wound Healing

Vaibhav      Rastogi; Mayur      Porwal; Athar      Aalam
Abstract

Background: Nanotechnology-based polyherbal drug delivery systems are considered a new and rapidly emerging area in the pharmaceutical field. They improved the drug loading capacity or enhanced encapsulation efficiency of herbal drugs and thus improved permeation efficiency, accelerated wound healing, promoted tissue remodelling, and reduced scarring.
Objective: A wound on the skin is an injury of the skin tissues that arises due to a cut or damage and also by an impact, blow, or other forces like a cut, surgery, chemical, heat, cold, friction, or illness like leg ulcers or carcinomas. These wounds result in the loss of skin's protective function by the removal of epithelium or connective tissues (i.e., muscle, bone, nerves). The four sequential but overlapping phases of the typical wound healing process are hemostasis, inflammation, proliferation, and remodeling. By encouraging the growth and movement of fibroblasts and keratinocytes, as well as angiogenesis at the site of damage, it has been demonstrated that a polyherbal mixture composed of plant extraction accelerates the lesion recovery process. Polyherbal formulations contain phytoconstituents such as triterpenoids, flavonoids, coumarins, quinones, and carotenoids etc. All these phytoconstituents are used for anti-inflammatory, anti-microbial, antioxidant, and lesion recovery. At the same time, nanotechnology-based polyherbal formulation has the potential to overcome the limitations of traditional polyherbal formulation in wound healing. Wounds are better managed by polyherbal combination rather than an individual plant due to its synergism and fewer side effects. To include these polyherbal components and deliver them to the wound site in a more focused and sustained way, novel drug delivery systems are also being developed.
Conclusion: This review discussed many nanotechnology-based polyherbal topical formulations for efficient and faster wound healing and recovery. Nanotechnology-based polyherbal formulations prove their success in promoting wound healing which is a unique approach to improving wound care and development of healthy skin.
[1]
Dubey, S.; Dixit, A.K. Preclinical evidence of polyherbal formulations on wound healing: A systematic review on research trends and perspectives. J. Ayurveda Integr. Med.,  2023, 14(2), 100688.
 [http://dx.doi.org/10.1016/j.jaim.2023.100688] [PMID: 36841194]

[2]
Gharbia, F.Z.; Abouhashem, A.S.; Moqidem, Y.A.; Elbaz, A.A.; Abdellatif, A.; Singh, K.; Sen, C.K.; Azzazy, H.M.E. Adult skin fibroblast state change in murine wound healing. Sci. Rep.,  2023, 13(1), 886.
 [http://dx.doi.org/10.1038/s41598-022-27152-4] [PMID: 36650180]

[3]
Sandoz, H. An overview of the prevention and management of wound infection. Nurs. Stand.,  2022, 37(10), 75-82.
 [http://dx.doi.org/10.7748/ns.2022.e11889] [PMID: 36039670]

[4]
Belachew, T.F.; Asrade, S.; Geta, M.; Fentahun, E. In vivo evaluation of wound healing and anti-inflammatory activity of 80% methanol crude flower extract of hagenia abyssinica (Bruce) J.F. Gmel in Mice. Evid. Based Complement. Alternat. Med.,  2020, 2020, 9645792.

[5]
Saghi, S.; Rinoldi, C.; Kristo, N. Drug Delivery systems and materials for wound healing applications. Physiol. Behav.,  2019, 176(3), 139-148.

[6]
Yang, S.; Gu, Z.; Lu, C.; Zhang, T.; Guo, X.; Xue, G.; Zhang, L. Neutrophil extracellular traps are markers of wound healing impairment in patients with diabetic foot ulcers treated in a multidisciplinary setting. Adv. Wound Care,  2020, 9(1), 16-27.
 [http://dx.doi.org/10.1089/wound.2019.0943] [PMID: 31871827]

[7]
Leavitt, T.; Hu, M.S.; Marshall, C.D.; Barnes, L.A.; Lorenz, H.P.; Longaker, M.T. Scarless wound healing: Finding the right cells and signals. Cell Tissue Res.,  2016, 365(3), 483-493.
 [http://dx.doi.org/10.1007/s00441-016-2424-8] [PMID: 27256396]

[8]
Sun, H.; Saeedi, P.; Karuranga, S.; Pinkepank, M.; Ogurtsova, K.; Duncan, B.B.; Stein, C.; Basit, A.; Chan, J.C.N.; Mbanya, J.C.; Pavkov, M.E.; Ramachandaran, A.; Wild, S.H.; James, S.; Herman, W.H.; Zhang, P.; Bommer, C.; Kuo, S.; Boyko, E.J.; Magliano, D.J. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract.,  2022, 183, 109119.
 [http://dx.doi.org/10.1016/j.diabres.2021.109119] [PMID: 34879977]

[9]
Ud-Din, S.; Sebastian, A.; Giddings, P.; Colthurst, J.; Whiteside, S.; Morris, J.; Nuccitelli, R.; Pullar, C.; Baguneid, M.; Bayat, A. Angiogenesis is induced and wound size is reduced by electrical stimulation in an acute wound healing model in human skin. PLoS One,  2015, 10(4), e0124502.
 [http://dx.doi.org/10.1371/journal.pone.0124502] [PMID: 25928356]

[10]
Polaka, S.; Katare, P.; Pawar, B.; Vasdev, N.; Gupta, T.; Rajpoot, K. Emerging ROS-modulatingtechnologies for augmentationof the wound healing process. ACS Omega,  2022, 7(35), 30657.

[11]
Dunnill, C.; Patton, T.; Brennan, J.; Barrett, J.; Dryden, M.; Cooke, J.; Leaper, D.; Georgopoulos, N.T. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS‐modulating technologies for augmentation of the healing process. Int. Wound J.,  2017, 14(1), 89-96.
 [http://dx.doi.org/10.1111/iwj.12557] [PMID: 26688157]

[12]
Zhang, L.; Hao, M.; Yao, L.; Xing, C.; Wen, Q.; Zhang, Z.; Yu, J.; Wang, J.; Xing, D.; Zheng, T.; Chen, P. Sericin “hairpin structure”-based multifunctional anthocyanin nanoencapsulation for remodeling ROS-dependent cutaneous wound healing. Chem. Eng. J.,  2023, 475, 145863.
 [http://dx.doi.org/10.1016/j.cej.2023.145863]

[13]
Guo, S.; DiPietro, L.A. Factors affecting wound healing. J. Dent. Res.,  2010, 89(3), 219-229.
 [http://dx.doi.org/10.1177/0022034509359125] [PMID: 20139336]

[14]
Rowan, M.P.; Cancio, L.C.; Elster, E.A.; Burmeister, D.M.; Rose, L.F.; Natesan, S.; Chan, R.K.; Christy, R.J.; Chung, K.K. Burn wound healing and treatment: Review and advancements. Crit. Care,  2015, 19(1), 243.
 [http://dx.doi.org/10.1186/s13054-015-0961-2] [PMID: 26067660]

[15]
Clark, A; Imran, J; Madni, T; Wolf, SE Nutrition and metabolism in burn patients. Burn. Trauma.,  2017, 5, 11.
 [http://dx.doi.org/10.1186/s41038-017-0076-x]

[16]
Palmieri, B.; Vadalà, M.; Laurino, C. Nutrition in wound healing: Investigation of the molecular mechanisms, a narrative review. J. Wound Care,  2019, 28(10), 683-693.
 [http://dx.doi.org/10.12968/jowc.2019.28.10.683] [PMID: 31600106]

[17]
Kim, J.W.; Lim, C.W.; Kim, B. Effects of nicotine on corneal wound healing following acute alkali burn. PLoS One,  2017, 12(6), e0179982.
 [http://dx.doi.org/10.1371/journal.pone.0179982] [PMID: 28644870]

[18]
Balaji, S.M. Tobacco smoking and surgical healing of oral tissues: A review. Indian J. Dent. Res.,  2008, 19(4), 344-348.
 [http://dx.doi.org/10.4103/0970-9290.44540] [PMID: 19075440]

[19]
Jain, M.; Khadilkar, N.; De Sousa, A. Burn-related factors affecting anxiety, depression and self-esteem in burn patients: An exploratory study. Ann. Burns Fire Disasters,  2017, 30(1), 30-34.
 [PMID: 28592931]

[20]
Vileikyte, L. Stress and wound healing. Clin. Dermatol.,  2007, 25(1), 49-55.
 [http://dx.doi.org/10.1016/j.clindermatol.2006.09.005] [PMID: 17276201]

[21]
Davis, C.S.; Esposito, T.J.; Palladino-Davis, A.G.; Rychlik, K.; Schermer, C.R.; Gamelli, R.L. Implications of alcohol intoxication at the time of burn and smoke inhalation injury: An epidemiologic and clinical analysis. J. Burn Care Res.,  2013, 34(1), 120-126.

[22]
Szabo, G.; Mandrekar, P. A recent perspective on alcohol, immunity, and host defense. Alcohol. Clin. Exp. Res.,  2009, 33(2), 220-232.
 [http://dx.doi.org/10.1111/j.1530-0277.2008.00842.x] [PMID: 19053973]

[23]
Chumpolphant, S.; Suwatronnakorn, M.; Issaravanich, S.; Tencomnao, T.; Prasansuklab, A. Polyherbal formulation exerts wound healing, anti-inflammatory, angiogenic and antimicrobial properties: Potential role in the treatment of diabetic foot ulcers. Saudi J. Biol. Sci.,  2022, 29(7), 103330.
 [http://dx.doi.org/10.1016/j.sjbs.2022.103330] [PMID: 35721231]

[24]
Karole, S.; Shrivastava, S.; Thomas, S.; Soni, B.; Khan, S.; Dubey, J. Polyherbal formulation concept for synergic action: A review. JDDT,  2019, 9, 453-466.

[25]
Khan, A.D.; Rastogi, V.; Lavhale, P.M.; Jain, J. Novel approaches for herbal drug delivery in wound healing: A review. Indian J. Pharm. Sci.,  2022, 84(2), 247-260.

[26]
Little, C.V. Simply because it works better: Exploring motives for the use of medical herbalism in contemporary U.K. health care. Complement. Ther. Med.,  2009, 17(5-6), 300-308.
 [http://dx.doi.org/10.1016/j.ctim.2009.08.001] [PMID: 19942110]

[27]
Satturwar, P.M. Wound mealing activity of Chandanadi Yamak in rats. Indian J. Pharmaceut. Sci.,  2003, 65(3), 301-304.

[28]
Daswani, B.R.; Yegnanarayan, R. Immunomodulatory activity of septilin, a polyherbal preparation. Phytother. Res.,  1994, 16(2), 162-165.

[29]
Kumar, M.S.; Kirubanandan, S.; Sripriya, R.; Sehgal, P.K. Triphala promotes healing of infected full-thickness dermal wound. J. Surg. Res.,  2008, 144(1), 94-101.
 [http://dx.doi.org/10.1016/j.jss.2007.02.049] [PMID: 17662304]

[30]
Ciftciler, R.; Ciftciler, A.E.; Malkan, U.Y.; Haznedaroglu, I.C. Pharmacobiological management of hemostasis within clinical backgrounds via Ankaferd hemostat (Ankaferd blood stopper). SAGE Open Med.,  2020, 8.
 [http://dx.doi.org/10.1177/2050312120907811] [PMID: 32110403]

[31]
Pluemsamran, T.; Tripatara, P.; Phadungrakwittaya, R.; Akarasereenont, P.; Laohapand, T.; Panich, U. Redox mechanisms of Avs022, an oriental polyherbal formula, and its component herbs in protection against induction of matrix metalloproteinase-1 in uva-irradiated keratinocyte hacat cells. Evid.-. Based Complement Altern. Med.,  2013, 2013, 739473.

[32]
Fahimi, S.; Abdollahi, M.; Mortazavi, S.A.; Hajimehdipoor, H.; Abdolghaffari, A.H.; Rezvanfar, M.A. Wound healing activity of a traditionally used poly herbal product in a burn wound model in rats. Iran. Red Crescent Med. J.,  2015, 17(9), e19960.
 [http://dx.doi.org/10.5812/ircmj.19960] [PMID: 26473072]

[33]
Somayeh, N. Polyherbal combination for wound healing: Matricaria chamomilla L. and Punica granatum L. Daru,  2021, 133-145.

[34]
Kumar, K.S.; Jeslin, D.; Prathyusha, S.; Panigrahy, U.P.; Syed, S.H.; Gupta, J. Phytochemical screening and in vitro evaluation of wound healing activity. Polyherb. Preparat. Using Chick Embryo Model.,  2022, 13(8), 2110-2122.

[35]
Marta, S.; Gonz, E.; Iglesias, I.; Pilar, M.G. Pharmacological update properties of aloe vera and its major active constituents. Molecules,  2020, 20, 1-37.

[36]
de Macedo, L.M.; Santos, É.M.; Militão, L.; Tundisi, L.L.; Ataide, J.A.; Souto, E.B.; Mazzola, P.G. Rosemary (Rosmarinus officinalis L., syn Salvia rosmarinus Spenn.) and Its Topical Applications: A Review. Plants,  2020, 9(5), 651.
 [http://dx.doi.org/10.3390/plants9050651] [PMID: 32455585]

[37]
Givol, O.; Kornhaber, R.; Visentin, D.; Cleary, M.; Haik, J.; Harats, M. A systematic review of Calendula officinalis extract for wound healing. Wound Repair Regen.,  2019, 27(5), 548-561.
 [http://dx.doi.org/10.1111/wrr.12737] [PMID: 31145533]

[38]
Manzuoerh, R.; Reza, M.; Oryan, A.; Sonboli, A. Biomedicine and pharmacotherapy original article Effectiveness of topical administration of anethum graveolens essential oil on MRSA-infected wounds. Biomed. Pharmacother.,  2019, 109, 1650-1658.
 [http://dx.doi.org/10.1016/j.biopha.2018.10.117] [PMID: 30551419]

[39]
Minhal Alhashim, M.D.F.; Jamie Lombardo, M. Effect of topical garlic onwound healing and scarring: A clinical trial. Am. Soc. Dermatol. Surg.,  2019, 1-12.

[40]
Xu, C.; Chou, G.X.; Wang, Z.T. A new diterpene from the leaves of Andrographis paniculata Nees. Fitoterapia,  2010, 81(6), 610-613.
 [http://dx.doi.org/10.1016/j.fitote.2010.03.003] [PMID: 20230876]

[41]
Kabir, M.H.; Hasan, N.; Rahman, M.M.; Rahman, M.A.; Khan, J.A.; Hoque, N.T.; Bhuiyan, M.R.Q.; Mou, S.M.; Jahan, R.; Rahmatullah, M. A survey of medicinal plants used by the Deb barma clan of the Tripura tribe of Moulvibazar district, Bangladesh. J. Ethnobiol. Ethnomed.,  2014, 10(1), 19.
 [http://dx.doi.org/10.1186/1746-4269-10-19] [PMID: 24502444]

[42]
Mi, J.; Wu, C.; Li, C.; Xi, F.; Wu, Z.; Chen, W. Two new triterpenoids from Ampelopsis japonica (Thunb.). Makino. Nat. Prod. Res.,  2014, 28(1), 52-56.
 [http://dx.doi.org/10.1080/14786419.2013.838237] [PMID: 24274791]

[43]
Fu, J.; Wang, Z.; Huang, L.; Zheng, S.; Wang, D.; Chen, S.; Zhang, H.; Yang, S. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother. Res.,  2014, 28(9), 1275-1283.
 [http://dx.doi.org/10.1002/ptr.5188] [PMID: 25087616]

[44]
Chiu, C.Y.; Hsu, W.H.; Liu, H.K.; Liu, S.H.; Lin, Y.L. Prepared Rehmanniae Radix oligosaccharide regulates postprandial and diabetic blood glucose in mice. J. Funct. Foods,  2018, 41, 210-215.
 [http://dx.doi.org/10.1016/j.jff.2017.12.031]

[45]
Wong, M.W.; Leung, P.C.; Wong, W.C. Limb salvage in extensive diabetic foot ulceration-a preliminary clinical study using simple debridement and herbal drinks. Hong Kong Med. J.,  2001, 7(4), 403-407.

[46]
Kishore, B.; Siva Prasad, M.; Murthy, G.K. Comparison of the dermal wound healing of Centella asiatica extract impregnated collagen and crosslinked collagen scaffolds. J. Chem. Pharm. Res.,  2011, 3(3), 353-362.

[47]
Pithawala, N.A.; Jain, B. Journal of Advanced Scientific Research. Adv. Sci.,  2012, 1(2), 19-23.

[48]
Zhao, H.; Wang, X.; Li, W.; Koike, K.; Bai, H. A new minor homoisoflavonoid from Caesalpinia sappan. Nat. Prod. Res.,  2014, 28(2), 102-105.
 [http://dx.doi.org/10.1080/14786419.2013.847439] [PMID: 24128117]

[49]
Xu, X.; Li, X.; Zhang, L.; Liu, Z.; Pan, Y.; Chen, D.; Bin, D.; Deng, Q.; Sun, Y.U.; Hoffman, R.M.; Yang, Z.; Yuan, H. Enhancement of wound healing by the traditional chinese medicine herbal mixture sophora flavescens in a rat model of perianal ulceration. In Vivo,  2017, 31(4), 543-549.
 [http://dx.doi.org/10.21873/invivo.11092] [PMID: 28652418]

[50]
Dev, S.K.; Choudhury, P.K.; Srivastava, R.; Sharma, M. Antimicrobial, anti-inflammatory and wound healing activity of polyherbal formulation. Biomed. Pharmacother.,  2019, 111(111), 555-567.
 [http://dx.doi.org/10.1016/j.biopha.2018.12.075] [PMID: 30597309]

[51]
Stohs, S.J.; Bagchi, D. Antioxidant, anti‐inflammatory, and chemoprotective properties of acacia catechu heartwood extracts. Phytother. Res.,  2015, 29(6), 818-824.
 [http://dx.doi.org/10.1002/ptr.5335] [PMID: 25802170]

[52]
Salehi, B.; Rodrigues, C.F.; Peron, G.; Dall, S.; Sharifi-rad, J.; Azmi, L. Curcumin nanoformulations for antimicrobial and wound healing purposes. Phytother. Res.,  2020, 2021, 1-13.
 [PMID: 33587320]

[53]
Kant, V.; Jangir, B.L.; Sharma, M.; Kumar, V.; Joshi, V.G. Topical application of quercetin improves wound repair and regeneration in diabetic rats. Immunopharmacol. Immunotoxicol.,  2021, 43(5), 536-553.
 [http://dx.doi.org/10.1080/08923973.2021.1950758] [PMID: 34278923]

[54]
Assar, D.H.; Elhabashi, N. Wound healing potential of licorice extract in rat model: Antioxidants, histopathological, immunohistochemical and gene expression evidences. Biomed. Pharmacother.,  2021, 143, 112151.

[55]
Yadav, N.P.; Maan, P.; Yadav, K. Wound healing activity of Azadirachta indica A. juss stem bark in mice. Pharmacogn. Mag.,  2017, 13(50), 316.
 [http://dx.doi.org/10.4103/0973-1296.210163] [PMID: 28808399]

[56]
Lin, L.X.; Wang, P.; Wang, Y.T.; Huang, Y.; Jiang, L.; Wang, X.M. Aloe vera and Vitis vinifera improve wound healing in an in vivo rat burn wound model. Mol. Med. Rep.,  2016, 13(2), 1070-1076.
 [http://dx.doi.org/10.3892/mmr.2015.4681] [PMID: 26677006]

[57]
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

[58]
Kumar, M.; Keshwania, P.; Chopra, S.; Mahmood, S.; Bhatia, A. Therapeutic potential of nanocarrier-mediated delivery of phytoconstituents for wound healing: Their current status and future perspective. AAPS PharmSciTech,  2023, 24, 155.

[59]
Medina-Cruz, D.; Saleh, B.; Vernet-Crua, A.; Ajo, A.; Roy, A.K.; Webster, T.J. Drug-delivery nanocarriers for skin wound-healing applications. In: Wound Heal Tissue Repair, Regen Diabetes; Elsevier, 2020. 
 [http://dx.doi.org/10.1016/B978-0-12-816413-6.00022-8]

[60]
Bernal-Chávez, S.; Nava-Arzaluz, M.G.; Quiroz-Segoviano, R.I.Y.; Ganem-Rondero, A. Nanocarrier-based systems for wound healing. Drug Dev. Ind. Pharm.,  2019, 45(9), 1389-1402.
 [http://dx.doi.org/10.1080/03639045.2019.1620270] [PMID: 31099263]

[61]
de Souza, M.L.; dos Santos, W.M.; de Sousa, A.L.M.D.; de Albuquerque Wanderley Sales, V.; Nóbrega, F.P.; de Oliveira, M.V.G.; Rolim-Neto, P.J. Lipid nanoparticles as a skin wound healing drug delivery system: Discoveries and advances. Curr. Pharm. Des.,  2020, 26(36), 4536-4550.
 [http://dx.doi.org/10.2174/1381612826666200417144530] [PMID: 32303163]

[62]
Sandhu, S.K.; Kumar, S.; Raut, J.; Singh, M.; Kaur, S.; Sharma, G. Systematic development and characterization of novel, high drug-loaded, photostable, curcumin solid lipid nanoparticle hydrogel for wound healing. Antioxidants,  2021, 10(5)

[63]
Saporito, F.; Sandri, G.; Bonferoni, M.C.; Rossi, S.; Boselli, C.; Icaro Cornaglia, A.; Mannucci, B.; Grisoli, P.; Vigani, B.; Ferrari, F. Essential oil-loaded lipid nanoparticles for wound healing. Int. J. Nanomedicine,  2017, 13, 175-186.
 [http://dx.doi.org/10.2147/IJN.S152529] [PMID: 29343956]

[64]
Ainbinder, D.; Paolino, D.; Fresta, M.; Touitou, E. Drug delivery applications with ethosomes. J. Biomed. Nanotechnol.,  2010, 6(5), 558-568.
 [http://dx.doi.org/10.1166/jbn.2010.1152] [PMID: 21329048]

[65]
Kumar, S.; Kumar, A.; Kumar, N.; Singh, P.; Singh, T.U.; Singh, B.R.; Gupta, P.K.; Thakur, V.K. In vivo therapeutic efficacy of Curcuma longa extract loaded ethosomes on wound healing. Vet. Res. Commun.,  2022, 46(4), 1033-1049.
 [http://dx.doi.org/10.1007/s11259-022-09952-1] [PMID: 35796857]

[66]
Ferrara, F.; Benedusi, M.; Sguizzato, M.; Cortesi, R.; Baldisserotto, A.; Buzzi, R.; Valacchi, G.; Esposito, E. Ethosomes and transethosomes as cutaneous delivery systems for quercetin: A preliminary study on melanoma cells. Pharmaceutics,  2022, 14(5), 1038.
 [http://dx.doi.org/10.3390/pharmaceutics14051038] [PMID: 35631628]

[67]
Partoazar, N.; Darvishi, M.H.; Nasoohi, S.; Rezayat, S.M.; Bahador, A.A.K. Ethosomal curcumin promoted wound healing and reduced bacterial flora in second degree burn in rat. Drug Res.,  2016, 66(12), 660-665.
 [http://dx.doi.org/10.1055/s-0042-114034]

[68]
Agarwal, A.; Kharb, V.; Saharan, V.A. Process optimisation, characterisation and evaluation of resveratrol-phospholipid complexes using Box-Behnken statistical design. Int. Curr. Pharm. J.,  2014, 3(7), 301-308.
 [http://dx.doi.org/10.3329/icpj.v3i7.19079]

[69]
Varadkar, M.; Gadgoli, C. Preparation and evaluation of wound healing activity of phytosomes of crocetin from Nyctanthes arbor-tristis in rats. J. Tradit. Complement. Med.,  2022, 12(4), 354-360.
 [http://dx.doi.org/10.1016/j.jtcme.2021.10.002] [PMID: 35747356]

[70]
Al-Samydai, A.; Qaraleh, M.A.; Alshaer, W.; Al-Halaseh, L.K.; Issa, R.; Alshaikh, F.; Abu-Rumman, A.; Al-Ali, H.; Al-Dujaili, E.A.S. Preparation, characterization, wound healing, and cytotoxicity assay of pegylated nanophytosomes loaded with 6-gingerol. Nutrients,  2022, 14(23), 5170.
 [http://dx.doi.org/10.3390/nu14235170] [PMID: 36501201]

[71]
Pananchery, J.; Gadgoli, C. In-vivo evaluation of phytosomal gel of the petroleum ether extract of root bark of onosma echiodes for wound healing activity in rats. Indones. J. Pharm.,  2021, 32(4), 474-483.
 [http://dx.doi.org/10.22146/ijp.2351]

[72]
Wang, W.; Lu, K.; Yu, C.; Huang, Q.; Du, Y.Z. Nano-drug delivery systems in wound treatment and skin regeneration. J. Nanobiotechnology,  2019, 17(1), 82.
 [http://dx.doi.org/10.1186/s12951-019-0514-y] [PMID: 31291960]

[73]
Eid, H.M.; Ali, A.A.; Ali, A.M.A.; Eissa, E.M.; Hassan, R.M.; Abo El-Ela, F.I.; Hassan, A.H. Potential use of tailored citicoline chitosan-coated liposomes for effective wound healing in diabetic rat model. Int. J. Nanomedicine,  2022, 17(January), 555-575.
 [http://dx.doi.org/10.2147/IJN.S342504] [PMID: 35153481]

[74]
Cardoso-Daodu, I.M.; Ilomuanya, M.O.; Azubuike, C.P. Development of curcumin-loaded liposomes in lysine-collagen hydrogel for surgical wound healing. Beni. Suef Univ. J. Basic Appl. Sci.,  2022, 11(1)

[75]
Shimojo, A.A.M.; Fernandes, A.R.V.; Ferreira, N.R.E.; Sanchez-Lopez, E.; Santana, M.H.A.; Souto, E.B. Evaluation of the influence of process parameters on the properties of resveratrol-loaded NLC using 2(2) full factorial design. Antioxidants,  2019, 8(8)

[76]
Albaayit, S.F.A.; Abdullah, R.; Noor, M.H.M. Zerumbone-loaded nanostructured lipid carrier gel enhances wound healing in diabetic rats. Biomed. Res. Int.,  2022, 2022, 1129297.
 [http://dx.doi.org/10.1155/2022/1129297]

[77]
Lee, H.J.; Jeong, M.; Na, Y.G.; Kim, S.J.; Lee, H.K.; Cho, C.W. An EGF- and curcumin-co-encapsulated nanostructured lipid carrier accelerates chronic-wound healing in diabetic rats. Molecules,  2020, 25(20), 4610.
 [http://dx.doi.org/10.3390/molecules25204610] [PMID: 33050393]

[78]
Pradhan, M.; Alexander, A.; Singh, M.R.; Singh, D.; Saraf, S.; Saraf, S. Ajazuddin, Understanding the prospective of nano-formulations towards the treatment of psoriasis. Biomed. Pharmacother.,  2018, 107, 447-463.
 [http://dx.doi.org/10.1016/j.biopha.2018.07.156] [PMID: 30103117]

[79]
Barbosa, T.C.; Nascimento, L.É.D.; Bani, C.; Almeida, T.; Nery, M.; Santos, R.S.; Menezes, L.R.O.; Zielińska, A.; Fernandes, A.R.; Cardoso, J.C.; Jäger, A.; Jäger, E.; Sanchez-Lopez, E.; Nalone, L.; Souto, E.B.; Severino, P. Development, cytotoxicity and eye irritation profile of a new sunscreen formulation based on benzophenone-3-poly(ε-caprolactone) nanocapsules. Toxics,  2019, 7(4), 51.
 [http://dx.doi.org/10.3390/toxics7040051] [PMID: 31546707]

[80]
Na, Y.; Woo, J.; Choi, W.I.; Lee, J.H.; Hong, J.; Sung, D. α-Tocopherol-loaded reactive oxygen species-scavenging ferrocene nanocapsules with high antioxidant efficacy for wound healing. Int. J. Pharm.,  2021, 596, 120205.
 [http://dx.doi.org/10.1016/j.ijpharm.2021.120205] [PMID: 33486042]

[81]
Carletto, B.; Koga, A.Y.; Novatski, A.; Mainardes, R.M.; Lipinski, L.C.; Farago, P.V. Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing. Colloids Surf. B Biointerfaces,  2021, 203, 111720.
 [http://dx.doi.org/10.1016/j.colsurfb.2021.111720] [PMID: 33819820]

[82]
Almukainzi, M.; El-masry, T.A.; Negm, W.A.; Elekhnawy, E.; Saleh, A.; Sayed, A.E. Gentiopicroside PLGA nanospheres: Fabrication, in vitro characterization, antimicrobial action, and in vivo effect for enhancing wound healing in diabetic rats. Int. J. Nanomedicine,  2022, 17, 1203-1225.

[83]
Chen, G.; He, L.; Zhang, P.; Zhang, J.; Mei, X.; Wang, D.; Zhang, Y.; Ren, X.; Chen, Z. Encapsulation of green tea polyphenol nanospheres in PVA/alginate hydrogel for promoting wound healing of diabetic rats by regulating PI3K/AKT pathway. Mater. Sci. Eng. C,  2020, 110, 110686.
 [http://dx.doi.org/10.1016/j.msec.2020.110686] [PMID: 32204114]

[84]
Damiani, G.; Pacifico, A.; Linder, D.M.; Pigatto, P.D.M.; Conic, R.; Grada, A.; Bragazzi, N.L. Nanodermatology‐based solutions for psoriasis: State‐of‐the art and future prospects. Dermatol. Ther.,  2019, 32(6), e13113.
 [http://dx.doi.org/10.1111/dth.13113] [PMID: 31600849]

[85]
Zhou, P.; Zhou, H.; Shu, J.; Fu, S.; Yang, Z. Skin wound healing promoted by novel curcumin-loaded micelle hydrogel. Ann. Transl. Med.,  2021, 9(14), 1152-1152.
 [http://dx.doi.org/10.21037/atm-21-2872] [PMID: 34430593]

[86]
Mignani, S.; El Kazzouli, S.; Bousmina, M.; Majoral, J.P. Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: A concise overview. Adv. Drug Deliv. Rev.,  2013, 65(10), 1316-1330.
 [http://dx.doi.org/10.1016/j.addr.2013.01.001] [PMID: 23415951]

[87]
Rastogi, V.; Yadav, P.; Porwal, M.; Sur, S.; Verma, A. Dendrimer as nanocarrier for drug delivery and drug targeting therapeutics: A fundamental to advanced systematic review. Inte. J. Polym. Mater. Polym. Biomater.,  2022, 734, 310-332.

[88]
Gupta, P.; Sheikh, A.; Abourehab, M.A.S. Amelioration of full-thickness wound using hesperidin loaded dendrimer-based hydrogel bandages. Biosensors,  2024, 12(7), 462.

[89]
Almatroudi, A. Silver nanoparticles: Synthesis, characterisation and biomedical applications. Open Life Sci.,  2020, 15(1), 819-839.
 [http://dx.doi.org/10.1515/biol-2020-0094] [PMID: 33817269]

[90]
Muthukumar, B.; Nandini, M.S.; Elumalai, P.; Balakrishnan, M.; Satheeshkumar, A.; Alsalhi, M.S. Enhancement of cell migration and wound healing by nano-herb ointment formulated with biosurfactant, silver nanoparticles and Tridax procumbens. Front. Microbiol.,  2023, 14, 1225769.
 [http://dx.doi.org/10.3389/fmicb.2023.1225769]

[91]
Orlowski, P.; Zmigrodzka, M.; Tomaszewska, E.; Ranoszek-Soliwoda, K.; Czupryn, M.; Antos-Bielska, M.; Szemraj, J.; Celichowski, G.; Grobelny, J.; Krzyzowska, M. Tannic acid-modified silver nanoparticles for wound healing: The importance of size. Int. J. Nanomedicine,  2018, 13, 991-1007.
 [http://dx.doi.org/10.2147/IJN.S154797] [PMID: 29497293]

[92]
Korani, S; Rashidi, K; Hamelian, M; Jalalvand, AR; Tajehmiri, A; Korani, M Evaluation of antimicrobial and wound healing effects of gold nanoparticles containing Abelmoschus esculentus (L.) aqueous extract. Bioinorg. Chem. Appl., 2021.

[93]
Hashem, A.H.; Shehabeldine, A.M.; Ali, O.M.; Salem, S.S. Synthesis of chitosan-based gold nanoparticles: Antimicrobial and wound-healing activities. Polymers ,  2022, 14(11), 2293.
 [http://dx.doi.org/10.3390/polym14112293] [PMID: 35683965]

[94]
Vazquez, N.I.; Gonzalez, Z.; Ferrari, B.; Castro, Y. Synthesis of mesoporous silica nanoparticles by sol-gel as nanocontainer for future drug delivery applications. Bol. Soc. Esp. Ceram. Vidr.,  2017, 56(3), 139-145.
 [http://dx.doi.org/10.1016/j.bsecv.2017.03.002]

[95]
Fayez Hamam, A.N. Curcumin-loaded mesoporous silica particles as wound-healing agent: An in vivo study. Saudi J. Med. Med. Sci.,  2017, 260-267.

[96]
Jia, Y.; Zhang, H.; Yang, S.; Xi, Z.; Tang, T.; Yin, R.; Zhang, W. Electrospun PLGA membrane incorporated with andrographolide-loaded mesoporous silica nanoparticles for sustained antibacterial wound dressing. Nanomedicine,  2018, 13(22), 2881-2899.
 [http://dx.doi.org/10.2217/nnm-2018-0099] [PMID: 30427768]

[97]
Rastogi, V.; Yadav, P.; Bhattacharya, S.S.; Mishra, A.K.; Verma, N.; Verma, A.; Pandit, J.K. Carbon nanotubes: An emerging drug carrier for targeting cancer cells. J. Drug Deliv.,  2014, 2014, 1-23.
 [http://dx.doi.org/10.1155/2014/670815] [PMID: 24872894]

[98]
Yadav, P.; Rastogi, V.; Kumar Mishra, A.; Verma, A. Carbon nanotube: A versatile carrier for various biomedical applications. Drug Deliv. Lett.,  2014, 4(2), 156-169.
 [http://dx.doi.org/10.2174/2210303103666131220234222]

[99]
Rahman, M.A.; Barkat, H.A.; Harwansh, R.K.; Deshmukh, R. Carbon-based nanomaterials: Carbon nanotubes, graphene, fullerenes for the control of burn infections and wound healing. Curr. Pharm. Biotechnol.,  2022, 23(12), 1483-1496.

[100]
Salleh, A.; Fauzi, M.B. The in vivo, in vitro and in ovo evaluation of quantum dots in wound healing: A review. Polymers,  2021, 13(2), 191.
 [http://dx.doi.org/10.3390/polym13020191] [PMID: 33430272]

[101]
Xu, S.; Chang, L.; Hu, Y.; Zhao, X.; Huang, S.; Chen, Z.; Ren, X.; Mei, X. Tea polyphenol modified, photothermal responsive and ROS generative black phosphorus quantum dots as nanoplatforms for promoting MRSA infected wounds healing in diabetic rats. J. Nanobiotechnology,  2021, 19(1), 362.
 [http://dx.doi.org/10.1186/s12951-021-01106-w] [PMID: 34758829]

[102]
Donnelly, R.F.; Singh, T.R.R.; Woolfson, A.D. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety. Drug Deliv.,  2010, 17(4), 187-207.
 [http://dx.doi.org/10.3109/10717541003667798] [PMID: 20297904]

[103]
Larrañeta, E.; Lutton, R.E.M.; Woolfson, A.D.; Donnelly, R.F. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater. Sci. Eng. Rep.,  2016, 104, 1-32.
 [http://dx.doi.org/10.1016/j.mser.2016.03.001]

[104]
Yang, J.; Wang, X.; Wu, D.; Yi, K.; Zhao, Y. Yunnan Baiyao-loaded multifunctional microneedle patches for rapid hemostasis and cutaneous wound healing. J. Nanobiotechnology,  2023, 21(1), 178.
 [http://dx.doi.org/10.1186/s12951-023-01936-w] [PMID: 37280566]

[105]
Chi, J.; Sun, L.; Cai, L.; Fan, L.; Shao, C.; Shang, L.; Zhao, Y. Chinese herb microneedle patch for wound healing. Bioact. Mater.,  2021, 6(10), 3507-3514.
 [http://dx.doi.org/10.1016/j.bioactmat.2021.03.023] [PMID: 33817424]

[106]
Sharda, D.; Kaur, P.; Choudhury, D. Protein-modified nanomaterials: Emerging trends in skin wound healing. Discover Nano.,  2023, 18, 127.
 [http://dx.doi.org/10.1186/s11671-023-03903-8]

[107]
Agarwal, Y.; Rajinikanth, P.S.; Ranjan, S.; Tiwari, U.; Balasubramnaiam, J.; Pandey, P.; Arya, D.K.; Anand, S.; Deepak, P. Curcumin loaded polycaprolactone-/polyvinyl alcohol-silk fibroin based electrospun nanofibrous mat for rapid healing of diabetic wound: An in-vitro and in-vivo studies. Int. J. Biol. Macromol.,  2021, 176, 376-386.
 [http://dx.doi.org/10.1016/j.ijbiomac.2021.02.025] [PMID: 33561460]

[108]
Pathan, I.B.; Munde, S.J.; Shelke, S.; Ambekar, W.; Mallikarjuna Setty, C. Curcumin loaded fish scale collagen-HPMC nanogel for wound healing application: Ex-vivo and In-vivo evaluation. Int. J. Polym. Mater.,  2019, 68(4), 165-174.
 [http://dx.doi.org/10.1080/00914037.2018.1429437]

[109]
Magda Bayoumi, B-S.U. Evaluation of diabetic foot wound healing using hydrogel/nano silver-based dressing vs. Traditional dressing.  NCT04834245, 2021.

[110]
University, C. Effect of nano-bio fusion gel on palatal wound healing after free gingival graft harvest. NCT05442359, 2023.

[111]
Chen, M.; Kumar, S.; Anselmo, A.C.; Gupta, V.; Slee, D.H. Muraski, JA Topical delivery of Cyclosporine A into the skin using SPACE-peptide. J. Control. Release,  2015, 199, 190-197.

[112]
Zhang, Y.T.; Feng, N-P.; Shen, L-N.; Zhao, J-H. Evaluation of psoralen ethosomes for topical delivery in rats by using in vivo microdialysis. Int. J. Nanomedicine,  2014, 9, 669-678.
 [http://dx.doi.org/10.2147/IJN.S57314] [PMID: 24489470]

[113]
Wadhwa, S.; Singh, B.; Sharma, G.; Raza, K.; Katare, O.P. Liposomal fusidic acid as a potential delivery system: A new paradigm in the treatment of chronic plaque psoriasis. Drug Deliv.,  2016, 23(4), 1204-1213.
 [http://dx.doi.org/10.3109/10717544.2015.1110845] [PMID: 26592918]

[114]
Nagle, A.; Goyal, A.K.; Kesarla, R.; Murthy, R.R. Efficacy study of vesicular gel containing methotrexate and menthol combination on parakeratotic rat skin model. J. Liposome Res.,  2011, 21(2), 134-140.
 [http://dx.doi.org/10.3109/08982104.2010.492476] [PMID: 20557280]

[115]
Ourique, A.F.; Pohlmann, A.R.; Guterres, S.S.; Beck, R.C.R. Tretinoin-loaded nanocapsules: Preparation, physicochemical characterization, and photostability study. Int. J. Pharm.,  2008, 352(1-2), 1-4.
 [http://dx.doi.org/10.1016/j.ijpharm.2007.12.035] [PMID: 18249513]

[116]
Marchiori, M.L.; Lubini, G.; Dalla Nora, G.; Friedrich, R.B.; Fontana, M.C.; Ourique, A.F.; Bastos, M.O.; Rigo, L.A.; Silva, C.B.; Tedesco, S.B.; Beck, R.C.R. Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: Preparation, characterization, and in vitro drug release study. Drug Dev. Ind. Pharm.,  2010, 36(8), 962-971.
 [http://dx.doi.org/10.3109/03639041003598960] [PMID: 20590450]

[117]
Lapteva, M.; Mondon, K.; Möller, M.; Gurny, R.; Kalia, Y.N. Polymeric micelle nanocarriers for the cutaneous delivery of tacrolimus: A targeted approach for the treatment of psoriasis. Mol. Pharm.,  2014, 11(9), 2989-3001.
 [http://dx.doi.org/10.1021/mp400639e] [PMID: 25057896]

[118]
Knudsen, N.Ø.; Jorgensen, L.; Hansen, J.; Vermehren, C.; Frokjaer, S.; Foged, C. Targeting of liposome-associated calcipotriol to the skin: Effect of liposomal membrane fluidity and skin barrier integrity. Int. J. Pharm.,  2011, 416(2), 478-485.
 [http://dx.doi.org/10.1016/j.ijpharm.2011.03.014] [PMID: 21419203]

[119]
Pandi, P.; Jain, A.; Kommineni, N.; Ionov, M.; Bryszewska, M.; Khan, W. Dendrimer as a new potential carrier for topical delivery of siRNA: A comparative study of dendriplex vs. lipoplex for delivery of TNF-α siRNA. Int. J. Pharm.,  2018, 550(1-2), 240-250.
 [http://dx.doi.org/10.1016/j.ijpharm.2018.08.024] [PMID: 30165098]

[120]
Avasatthi, V.; Pawar, H.; Dora, C.P.; Bansod, P.; Gill, M.S.; Suresh, S. A novel nanogel formulation of methotrexate for topical treatment of psoriasis: optimization, in vitro and in vivo evaluation. Pharm. Dev. Technol.,  2016, 21(5), 554-562.
 [http://dx.doi.org/10.3109/10837450.2015.1026605] [PMID: 26024238]

[121]
Doktorovová, S.; Araújo, J.; Garcia, M.L.; Rakovský, E.; Souto, E.B. Formulating fluticasone propionate in novel PEG-containing nanostructured lipid carriers (PEG-NLC). Colloids Surf. B Biointerfaces,  2010, 75(2), 538-542.
 [http://dx.doi.org/10.1016/j.colsurfb.2009.09.033] [PMID: 19879736]

[122]
Pradhan, M.; Singh, D.; Singh, M.R. Development characterization and skin permeating potential of lipid based novel delivery system for topical treatment of psoriasis. Chem. Phys. Lipids,  2015, 186, 9-16.
 [http://dx.doi.org/10.1016/j.chemphyslip.2014.11.004] [PMID: 25447290]

[123]
Agrawal, U.; Gupta, M.; Vyas, S.P. Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of psoriasis. Artif. Cells Nanomed. Biotechnol.,  2015, 43(1), 33-39.
 [http://dx.doi.org/10.3109/21691401.2013.832683] [PMID: 24040836]

[124]
Sonawane, R.; Harde, H.; Katariya, M.; Agrawal, S.; Jain, S. Solid lipid nanoparticles-loaded topical gel containing combination drugs: An approach to offset psoriasis. Expert Opin. Drug Deliv.,  2014, 11(12), 1833-1847.
 [http://dx.doi.org/10.1517/17425247.2014.938634] [PMID: 25078031]

[125]
Ahn, S.; Chantre, C.; Gonzalez, G.M. Parker, KK Biomimetic pro - Regenerative scaffolds and methods of use thereof.  
          U.S. Patent 2020/0376170 A1, 2020.

[126]
Weller, K-A.C. A topical herbal healing formulation. W.O. Patent 2017060535A1, 2020.

[127]
Tomulewicz, M. Herbal preparation for accelerating wounds and skin inflammations healing, especially for treatment of herpes and acne, and its application., 2019.

[128]
Tomulewicz, M. HERBAL PREPARATION FOR ACCELERATING WOUNDS AND SKIN INFLAMMATIONS HEALING AND ITS APPLICATION. U.S. Patent 10213469B22018, 

[129]
Shraibom, N. Herbal combinations for wound healing in fibroblasts. U.S. Patent 20180185428A1, 2018.

[130]
Yates Kenneth, M. Antimicrobial silver and acemannan composition for the treatment of wounds or lesions or burns. Molecules,  2008, 13(8), 1599-1616.
 [PMID: 18794775]

[131]
 A nanobiocomposite formulation for wound healing and a process for the preparation thereof. W.O. Patent 2017122224A1, 2017.

[132]
Praveen, Walia A multifunctional natural wound healing matrix. W.O. Patent 2014147638A1, 2014.

[133]
Majidi, F; Mehdi, S  Electro spun nanofibrous wound dressing and amethod of synthesizing the same. U.S. Patnet 20130150763A1, 2015.

[134]
Tepzz, T; Permettant, C  Les, DET Cream for burns. 2015.
Cite As
The Natural Products Journal

A Review on Nanocarrier-based Polyherbal Drug Delivery Systems for Wound Healing

Abstract
