Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 This article focus on CSCaCO3NP as porous nontoxic drug nanocarrier that could enhance the effectiveness of the drug. + 1567 word(s) 1567 2020-10-10 10:40:33 |
2 format correction -295 word(s) 1272 2020-11-23 08:11:42 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Muhammad Mailafiya, M.; Abubakar, K.; Danmaigoro, A.; Musa Chiroma, S.; Bin Abdul Rahim, E.; Aris Mohd Moklas, M.; Abu Bakar Zakaria, Z. Cockle Shell-Derived Calcium Carbonate Nanoparticles. Encyclopedia. Available online: (accessed on 05 December 2023).
Muhammad Mailafiya M, Abubakar K, Danmaigoro A, Musa Chiroma S, Bin Abdul Rahim E, Aris Mohd Moklas M, et al. Cockle Shell-Derived Calcium Carbonate Nanoparticles. Encyclopedia. Available at: Accessed December 05, 2023.
Muhammad Mailafiya, Maryam, Kabeer Abubakar, Abubakar Danmaigoro, Samaila Musa Chiroma, Ezamin Bin Abdul Rahim, Mohamad Aris Mohd Moklas, Zuki Abu Bakar Zakaria. "Cockle Shell-Derived Calcium Carbonate Nanoparticles" Encyclopedia, (accessed December 05, 2023).
Muhammad Mailafiya, M., Abubakar, K., Danmaigoro, A., Musa Chiroma, S., Bin Abdul Rahim, E., Aris Mohd Moklas, M., & Abu Bakar Zakaria, Z.(2020, November 19). Cockle Shell-Derived Calcium Carbonate Nanoparticles. In Encyclopedia.
Muhammad Mailafiya, Maryam, et al. "Cockle Shell-Derived Calcium Carbonate Nanoparticles." Encyclopedia. Web. 19 November, 2020.
Cockle Shell-Derived Calcium Carbonate Nanoparticles

This entry is terms to explain the importance of CSCaCO3NPs as drug nanocarrier with emphases on cytotoxicity, pharmacokinetics, slow biodegradation, pH sensitive, safety and efficacy in addition to the good biocompatibility and osteoconductivity as bone substitute. The synthesis of stimuli responsive nanocarrier with sustain release is a significant innovation in the field of nanomedicine in which biogenic biodegradable inorganic CSCaCO3NPs for the delivery of both hydrophilic and hydrophobic drugs could be employed.  

Cockleshell drug delivery calcium carbonate therapeutics

1. Introduction 

Recent developments in advanced active delivery systems for drugs, elicited by nanotechnology had led to their application in modern science [1][2][3]. Conventional free-drug delivery through subcutaneous, oral, intramuscular or intravenous routes, has led to drug biodistribution in the body via blood capillaries and accumulation to a certain concentration at the target site to exert therapeutic effects [2]. However, there is a paucity of the desirable effects of these free drugs due to poor bioavailability as a result of insolubility, hydrophobic nature, poor absorption and rapid metabolism [3]. In the quest to overcome some limitations associated with these therapeutic agents, the fast-growing field of nanotechnology focuses on diverse exploratory ways for researchers in the field of biomedical and pharmaceutical sciences. Advanced nanotechnology has paved ways for the use of convenient, affordable and noncomplex methods for synthesizing different nanoparticles from a range of abundant natural biomaterials and complex organic materials for industrial and medicinal purposes [4].

Nanoparticles are minute ultrafine particles with dimensions ranging between 1–1000 nm (usually 5–350 nm in diameter). They can be produced using different types of biocompatible materials [5][6]. The use of nanoparticle-based drug carrier systems in the field of nanotechnology has become an area with a novel attention in the past few decades due to their unique and superior properties that enable functionalisation at both molecular and cellular levels [7][8][9][10][11][12][13][14]. Advanced novel drug delivery systems help to boost the efficacy of therapeutic drugs as well as minimising the rate of a drug's off targeted effects thereby preventing cytotoxicity to normal cells [8]. This brought forth a useful enhanced therapeutic efficacy through suitable modifications of a drug's bioavailability, pharmacokinetics and serum stability [9] as well as specificity in drug release which is elicited by response to a particular stimulus such as ultrasound intensity, pH, magnetism and temperature [10].

Cockle (Anadara granosa) with a Malaysian native name "kerang" belongs to the family of Cardiidae, which is a small, salt water edible clam that is popularly referred to as marine bivalve mollusc [11]. It is native to coastal regions of South East Asia (Malaysia, Thailand and Indonesia). These important sea species mostly dwells in coastal area and it is a common important source of calcium carbonate (CaCO3) with abundant biomaterials for biomedical purposes [12]. It has tremendous striking properties, also it is cheap and readily available with abundant high quality and pure CaCO3 in aragonite polymorphic form, which is used in drug delivery [4].

CaCO3 is an inorganic calcium salt originated from varieties of shelled molluscs, limestone, coccolithophores, plant ashes, chalk and marble which is recently being studied in the field of nanotechnology as one of the potential porous biocompatible and pH sensitive material [6][11]. Further, its solubility has been stated to be exponentially and inversely proportional to its pH [10][13]. Its physicochemical properties are easily regulated as well as surface morphological chemistry and method of production [14][15]. CaCO3 is one of the emerging inorganic nanoparticles which exists in three different polymorphs such as vaterite, aragonite, and calcites [15]. It also possess a peculiar property of low thermodynamic stability thus, its size and shape are in concordance with the method and conditions of laboratory preparations [11]. In addition, numerous studies in recent years, were carried out on its toxicity to prove its wide safety margin both in vivo and in vitro [10][16][17][18][19][20].

2. Nanotechnology and Nanomedicine

Over the past few decades, nanotechnology has gained tremendous attention with good future prospects focusing more on nanoparticles, which is basically the bedrock of nanotechnology [1][13][17][21][22][23][24]. Nanotechnology is an important aspect of science that focuses on the continuous designing and manipulation of materials (atoms and molecules) to produce structures at the nanometre scale size ranging from smaller nanometre to 100 nm with unaltered initial unique features of the material used, with broad nanoscale schemes in clinical applications for therapeutic, protective as well as diagnostic purposes [8][25]. The entire application of nanotechnology from the synthesis processes, control release profiling, monitoring of biological processes and diagnosis is referred to as "Nano-medicine" [8]. This comprehensively means a process of transformation and encapsulation of a drug's molecules using nanostructures with or without the help of a carrier materials, masking some inherent drawbacks and limitations of free drugs such as poor bioavailability, hydrophobicity, high dosages, rapid assimilation, short half-life of photo degradation, poor selectivity as well as off targeted effects [26]. Conventional utilization of free drugs portrays poor bioavailability, low efficacy, non-selectivity and undesirable side effects [8][27]. For the past few years, a considerably large number of poorly soluble drug candidates has gradually increased as a result of the use of high-throughput screening and combinatory chemistry in drug discovery [28][29][30]. Approximately 70% of marketed drugs and many new chemical drug candidates, medicinal herbs as well as food supplements sometimes fails to be absorbed in the gastrointestinal tract (GIT) and often possess poor intravenous circulation and muscular tissue absorption after administration [31]. The low solubility nature of drugs limits their dissolution rate leading to a variety of issues which consequently results in low bioavailability as well as an erratic absorption pattern of drugs in biological systems [32]. However, an alternative way of overcoming such problems can be achieved by dose escalation although, this could result in undesirable effects associated with increased toxicity leading to patient's non-compliance [30]. Delivering therapeutic compound to the desirable localised site is quite challenging for the treatment of many ailments [27]. However, the application of nanomedicine have currently helped to overcome some of the problems of free dugs for therapeutic purpose [33]. This could be due to the uniqueness of the physicochemical properties presented by nanoparticles such as; (a) increased solubility; (b) increased drug pharmacokinetics; (c) co-delivery of multiple drugs to the same specific location at the same time (synergistic treatment); (d) enhanced bio distribution and bioavailability of drug to the targeted area; (e) improved drug permeability and retention effects; (f) increased specificity of drugs to targeted site of interest; (g) increased surface area to volume ratio and (h) decreased patient-to-patient variability [2][34].

3. Conclusions

Veteran CSCaCO3NP has recently been synthesized and developed by quite a number of scholars in the quest to overcome some biocompatibility issues associated with some therapeutic agents. The CSCaCO3NP among other nanoparticles, is one of the potential and toxic free nanoparticles due to its unique properties such as biodegradability, bioavailability, biocompatibility, large surface area and porosity nature. The top-down method adopted for the synthesis of CSCaCO3NP involves the use of simple suitable available and more cost-effective instruments in the presence of BS-12 surfactant, which is a biomineralization catalyst. CSCaCO3NP is applicable for the delivery of anticancer and antibiotics drugs with a remarkably effective role in bone remodelling and osteoporosis therapy. Nevertheless, the slow biodegradable nature of powdered cockle shells qualified its usage as an alternative construction material for artificial reef. Previous research literature highlighted some advantages of CSCaCO3NP as a nanocarrier for anti-cancer drugs and antibiotic focusing more on intravenous administration. Hence, the current review recommends more research on kinetic release mechanism of CSCaCO3NP in various different pH with emphasis on high acidic pH. Further improvement and modifications on the method of synthesising CSCaCO3NP to prevent problems of agglomerations is expected. Finally, research focus should be made on CSCaCO3NP as carrier system for various therapeutic agents such as anti-oxidants, anti-inflammatories using different routes of administration for effective applications at large.


  1. Hasan, S.; Hasan, S. A Review on Nanoparticles: Their Synthesis and Types A Review on Nanoparticles: Their Synthesis and Types. Res. J. Recent Sci. 2015, 4, 7–10.
  2. Shen, S.; Wu, Y.; Liu, Y.; Wu, D. High drug-loading nanomedicines: Progress, current status, and prospects. Int. J. Nanomedicine 2017, 12, 4085–4109.
  3. Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of Curcumin: Problems and promises. Mol. Pharmacol. 2007, 4, 807–818.
  4. Mohd Abd Ghafar, S.L.; Hussein, M.Z.; Rukayadi, Y.; Abu Bakar Zakaria, M.Z. Surface-functionalized cockle shell – based calcium carbonate aragonite polymorph as a drug nanocarrier. Nanotechnol. Sci. Appl. 2017, 10, 79–94.
  5. Dizaj, S.M.; Jafari, S.; Khosroushahi, A.Y. A sight on the current nanoparticle-based gene delivery vectors. Nanoscale Res. Lett. 2014, 9, 1–9.
  6. Dizaj, S.M.; Barzegar-Jalali, M.; Zarrintan, M.H.; Adibkia, K.; Lotfipour, F. Calcium Carbonate Nanoparticles; Potential in Bone and Tooth Disorders. Pharm. Sci. 2015, 20, 175–182.
  7. Küther, J.; Seshadri, R.; Knoll, W.; Tremel, W. Templated growth of calcite, vaterite and aragonite crystals on self-assembled monolayers of substituted alkylthiols on gold. J. Mater. Chem. 1998, 8, 641–650.
  8. Moghimi, S.M. Nanomedicine: current status and future prospects. FASEB J. 2005, 19, 311–330.
  9. Maleki Dizaj, S.; Barzegar-Jalali, M.; Zarrintan, M.H.; Adibkia, K.; Lotfipour, F. Calcium carbonate nanoparticles as cancer drug delivery system. Expert Opin. Drug Deliv. 2015, 12, 1649–1660.
  10. Fu, W.; Mohd Noor, M.H.; Yusof, L.M.; Ibrahim, T.A.T.; Keong, Y.S.; Jaji, A.Z.; Zakaria, M.Z.A.B. In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma. J. Exp. Nanosci. 2017, 12, 166–187.
  11. Jaji, A.Z.; Bakar, M.Z.; Mahmud, R.; Loqman, M.Y.; Hezmee, M.N.; Isa, T.; Wenliang, F.; Hammadi, N.I. Synthesis, characterization, and cytocompatibility of potential cockle shell aragonite nanocrystals for osteoporosis therapy and hormonal delivery. Nanotechnol. Sci. Appl. 2017, 10, 23–33.
  12. Awang-Hazmi, A.J.; Zuki, A.B.Z.; Noordin, M.M.; Jalila, A.; Norimah, Y. Mineral composition of the cockle (Anadara granosa) shells of West Coast of Peninsular Malaysia and it’s potential as biomaterial for use in bone repair. j. Amin Vet. Adv.. 2007, 6, 591–594.
  13. Wang, L.; Sondi, I.; Matijević, E. Preparation of uniform needle-like aragonite particles by homogeneous precipitation. J. Colloid Interface Sci. 1999, 218, 545–553.
  14. Rodríguez-Ruiz, I.; Delgado-López, J.M.; Durán-Olivencia, M.A.; Iafisco, M.; Tampieri, A.; Colangelo, D.; Prat, M.; Gómez-Morales, J. PH-responsive delivery of doxorubicin from citrate-apatite nanocrystals with tailored carbonate content. Langmuir 2013, 29, 8213–8221.
  15. Islam, K.N.; Bakar, M.Z.B.A.; Ali, M.E.; Hussein, M.Z.B.; Noordin, M.M.; Loqman, M.Y.; Miah, G.; Wahid, H.; Hashim, U. A novel method for the synthesis of calcium carbonate (aragonite) nanoparticles from cockle shells. Powder Technol. 2013, 235, 70–75.
  16. Jaji, A.Z.; Zakaria, Z.A.B.; Mahmud, R.; Loqman, M.Y.; Hezmee, M.N.M.; Abba, Y.; Isa, T.; Mahmood, S.K. Safety assessments of subcutaneous doses of aragonite calcium carbonate nanocrystals in rats. J. Nanoparticle Res. 2017, 19, 175.
  17. Danmaigoro, A.; Selvarajah, G.T.; Noor, M.H.M.; Mahmud, R.; Zakaria, M.Z.A.B. Development of cockleshell (Anadara granosa) derived CaCO3 nanoparticle for doxorubicin delivery. J. Comput. Theor. Nanosci. 2017, 14, 5074–5086.
  18. Hammadi, N.I.; Abba, Y.; Hezmee, M.N.M.; Razak, I.S.A.; Jaji, A.Z.; Isa, T.; Mahmood, S.K.; Zakaria, M.Z.A.B. Formulation of a Sustained Release Docetaxel Loaded Cockle Shell-Derived Calcium Carbonate Nanoparticles against Breast Cancer. Pharm. Res. 2017, 34, 1193–1203.
  19. Kamba, A.S.; Ismail, M.; Azmi Tengku Ibrahim, T.; Zakaria, Z.A.B. Biocompatibility of bio based calcium carbonate nanocrystals aragonite polymorph on nih 3T3 fibroblast cell line. African J. Tradit. Complement. Altern. Med. 2014, 11, 31–38.
  20. Hamidu, A.; Mokrish, A.; Mansor, R.; Shameha, I.; Razak, A.; Danmaigoro, A.; Jaji, A.Z.; Bakar, Z.A. Modi fi ed methods of nanoparticles synthesis in pH-sensitive nano-carriers production for doxorubicin delivery on MCF-7 breast cancer cell line. Int. J. Nanomed. 2019, 14, 3615–3627.
  21. Popović, Z.; Liu, W.; Chauhan, V.P.; Lee, J.; Wong, C.; Greytak, A.B.; Insin, N.; Nocera, D.G.; Fukumura, D.; Jain, R.K.; et al. A nanoparticle size series for invivo fluorescence imaging. Angew. Chemie Int. Ed. 2010, 49, 8649–8652.
  22. Alexis, F.; Pridgen, E.; Molnar, L.K.; Farokhzad, O.C. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 2008, 5, 505–515.
  23. Duan, J.; Mansour, H.M.; Zhang, Y.; Deng, X.; Chen, Y.; Wang, J.; Pan, Y.; Zhao, J. Reversion of multidrug resistance by co-encapsulation of doxorubicin and curcumin in chitosan/poly(butyl cyanoacrylate) nanoparticles. Int. J. Pharm. 2012, 426, 193–201.
  24. Zambrano, L.M.G.; Brandao, D.A.; Rocha, F.R.G.; Marsiglio, R.P.; Longo, I.B.; Primo, F.L.; Tedesco, A.C.; Guimaraes-Stabili, M.R.; Rossa, C. Local administration of curcumin-loaded nanoparticles effectively inhibits inflammation and bone resorption associated with experimental periodontal disease. Sci. Rep. 2018, 8, 1–11.
  25. Perret, P.; Bacot, S.; Gèze, A.; Gentil Dit Maurin, A.; Debiossat, M.; Soubies, A.; Blanc-Marquis, V.; Choisnard, L.; Boutonnat, J.; Ghezzi, C.; et al. Biodistribution and preliminary toxicity studies of nanoparticles made of Biotransesterified β–cyclodextrins and PEGylated phospholipids. Mater. Sci. Eng. C 2018, 85, 7–17.
  26. Zhao, P.; Wu, S.; Cheng, Y.; You, J.; Chen, Y.; Li, M.; He, C.; Zhang, X.; Yang, T.; Lu, Y.; et al. MiR-375 delivered by lipid-coated doxorubicin-calcium carbonate nanoparticles overcomes chemoresistance in hepatocellular carcinoma. Nanomedicine Nanotechnology, Biol. Med. 2017, 13, 2507–2516.
  27. Bhatia, S. Natural Polymer Drug Delivery Systems: Nanoparticles, Plants, and Algae; Spronger International Publishing: Basilea, Switzerland, 2016; pp. 1–225. ISBN 9783319411293.
  28. Christopher, A. lipinski Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 2000, 44, 235–249.
  29. Prashantha Kumar, B.R.; Soni, M.; Bharvi Bhikhalal, U.; Kakkot, I.R.; Jagadeesh, M.; Bommu, P.; Nanjan, M.J. Analysis of physicochemical properties for drugs from nature. Med. Chem. Res. 2010, 19, 984–992.
  30. Lu, Y.; Park, K. Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int. J. Pharm. 2013, 453, 198–214.
  31. Kawabata, Y.; Wada, K.; Nakatani, M.; Yamada, S.; Onoue, S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int. J. Pharm. 2011, 420, 1–10.
  32. Hörter, D.; Dressman, J. B Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv. Drug Deliv. Rev. 2002, 46, 75–87.
  33. Chen, Y.C.; Shie, M.Y.; Wu, Y.H.A.; Lee, K.X.A.; Wei, L.J.; Shen, Y.F. Anti-inflammation performance of curcumin-loaded mesoporous calcium silicate cement. J. Formos. Med. Assoc. 2017, 116, 679–688.
  34. Torchilin, V.P. Nanocarriers. Pharm. Res. 2007, 24, 2333–2334.
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , , , , ,
View Times: 390
Revisions: 2 times (View History)
Update Date: 23 Nov 2020