Cockle Shell-derived Calcium Carbonate Research Articles

Efficient Delivery of Recombinant Human Bone Morphogenetic Protein (Rhbmp-2) With Cockle Shell Derived Calcium Carbonate Nanoparticles (CaCO3NPs)

Bone morphogenetic protein-2 (BMP-2) has a significant function in the formation of cartilage and bones. Notably, dosing of only BMP-2 protein intravenously is ineffective. Persistent transportation of the stabilized BMP-2 through a carrier has been seen to be essential for enhancing the osteogenesis im pact of BMP-2. The current research built a new system of drug delivery by utilising cockle shell derived calcium carbonate nanoparticles (CaCO3NPs) and studied the efficacy of the delivery system on the recombinant human bone morphogenetic protein (rhBMP-2). rhBMP-2-CaCO3NPs nanoparticles were synthesised by means of a modest precipitation procedure along with mechanical grinding. Fourier-tran sform infrared spectroscopy, UV–Vis spectrophotometer, scanning electron microscope, X-ray powder diffraction, transmission electron microscope, and zeta potential were u tilised for characterising the conjugated rhBMP-2-CaCO3NPs . Cytotoxicity of rhBMP-2, CaCO3NPs and rhBMP-2-CaCO 3NPs was studied by utilising methylthiazol tetrazolium assay against fibroblast (Rat-1) cells in comparison to rhBMP-2 and CaCO3NPs. The outcomes signified bio-stability of CaCO3NPs and lower toxicity for Rat-1 cells. In summary, CaCO3NPs were prepared by a simp le precipitation process. The ensuing nanoparticles could competently entrap rhBMP-2 and generated stable rhBMP-2-CaCO3NPs. A sustained discharge of rhBMP-2 from t he CaCO3NPs was seen. CaCO3NPs loaded with r hBMP-2 demonstrated reasonable bio-compatibility. The outcomes indicated that CaCO3NPs may have significant ability as carrier of therapeutic proteins within bone tissue en gineering.

Cytotoxicity Studies of Curcumin Loaded-cockle Shell-derived Calcium Carbonate Nanoparticles

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possesses a wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attention. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Method: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Result: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at a higher dose of 500 μg/ml and 40 μg/ml, respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone- related ailments.

Curcumin-loaded cockle shell-derived calcium carbonate nanoparticles: A novel strategy for the treatment of lead-induced hepato-renal toxicity in rats.

Lead (Pb) toxicity affects the hepatic and renal systems resulting to homeostasis imbalance. Curcumin is a strong antioxidant but has restrained clinical applications due to its poor bioavailability. Nanomedicine showed promising potentials in drug delivery and has brought forth the use of cockle shell-derived aragonite calcium carbonate nanoparticles (CSCaCO3NP) to enhance the effectiveness and targeted delivery of curcumin (Cur). Thus, this study aimed at evaluating the therapeutic effect of curcumin-loaded CSCaCO3NP (Cur- CSCaCO3NP) on lead-induced hepato-renal toxicity in rats. Thirty-six male adults Sprague-Dawley rats were randomly assigned into five groups. All groups contained six rats each except for group A, which contained 12 rats. All rats apart from the rats in group A (control) were orally administered a flat dose of 50mg/kg of lead for four weeks. Six rats from group A and B were euthanized after four weeks of lead induction. Oral administration of curcumin (100mg/kg) for group C and Cur-CSCaCO3NP (50 and 100mg/kg) for groups D and E respectively, commenced immediately after 4weeks of lead induction which lasted for 4weeks. All rats were euthanized at the 8th week of the experiment. Further, biochemical, histological and hematological analysis were performed. The findings revealed a biochemical, hematological and histological changes in lead-induced rats. However, treatments with the Cur-CSCaCO3NP and free curcumin reversed the aforementioned changes. Although, Cur-CSCaCO3NP presented better therapeutic effects on lead-induced toxicity in rats when compared to free curcumin as there was significant improvements in hematological, biochemical and histological changes which is parallel with attenuation of oxidative stress. The findings of the current study hold great prospects for Cur-CSCaCO3NP as a novel approach for effective oral treatment of lead-induced hepato-renal impairments.

Evaluation of in vitro release kinetics and mechanisms of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles

Introduction: Curcumin has remarkable pharmacological activities but remains clinically constrained due to its poor bioavailability as a result of insolubility. This has necessitated the search for natural inorganic materials for curcumin delivery. Cockleshells are external hard materials of marine animals often treated as unwanted wastes, which are excellent sources of calcium carbonate. This study aimed to synthesize cockle shell-derived calcium carbonate (aragonite) nanoparticles (CSCaCO3NP) for delivery of curcumin and to evaluate its kinetic release in vitro. Methods: CSCaCO3NP was synthesized and conjugated with curcumin (Cur-CSCaCO3NP) using a simple top down approach and characterized for its physicochemical properties as a potential curcumin carrier. The in vitro release profile was assessed using the dialysis bag membrane method. The release data were fitted to Korsmeyer-Peppas, Zero order, and Higuchi models to evaluate the mechanism(s) of the release pattern. Results: A spherical shaped CSCaCO3NP with a surface area of 14.48+/-0.1 m2/g, with mean diameter size of 21.38+/-2.7 nm and zeta potential of -18.7 mV, was synthesized and found to have high loading content and encapsulation efficiency. The FT-IR and XRD revealed fewer observable changes on the peaks after conjugation. The profile of the in vitro kinetic release demonstrated a sustained release, and which was best fitted to the Higuchi equation model. Conclusion: The results of this study showed the capacity of the synthesized CSCaCO3NP to encapsulate curcumin efficiently with a stable release in vitro. This provides insight into and rationale for the potential of CSCaCO3NP for curcumin delivery. Therefore, CSCaCO3NP holds great prospects in the preclinical framework for enhancing curcumin efficacy in oral therapeutic applications.

Cockle Shell-Derived Calcium Carbonate (Aragonite) Nanoparticles: A Dynamite to Nanomedicine

Cockle shell is an external covering of small, salt water edible clams (Anadara granosa) that dwells in coastal area. This abundant biomaterial is hard, cheap and readily available with high content of calcium carbonate in aragonite polymorphic form. At present, cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NPs) with dual applications has remarkably drawn significant attention of researchers in nanotechnology as a nanocarrier for delivery of different categories of drugs and as bone scaffold due to its beneficial potentials such as biocompatibility, osteoconductivity, pH sensitivity, slow biodegradation, hydrophilic nature and a wide safety margin. In addition, CSCaCO3NP possesses structural porosity, a large surface area and functional group endings for electrostatic ion bonds with high loading capacity. Thus, it maintains great potential in the drug delivery system and a large number of biomedical utilisations. The pioneering researchers adopted a non-hazardous top-down method for the synthesis of CSCaCO3NP with subsequent improvements that led to the better spherical diameter size obtained recently which is suitable for drug delivery. The method is therefore a simple, low cost and environmentally friendly, which involves little procedural steps without stringent temperature management and expensive hazardous chemicals or any carbonation methods. This paper presents a review on a few different types of nanoparticles with emphasis on the versatile most recent advancements and achievements on the synthesis and developments of CSCaCO3NP aragonite with its applications as a nanocarrier for drug delivery in nanomedicine.

Targeted delivery of doxorubicin-loaded cockle shell-derived CaCO<SUB align="right">3 aragonite nanoparticles on dogs with solid tumours

The treatment of solid tumour remains a major challenge to oncologists. Even when chemotherapy is referred as the best treatment option thus associated with off targeted effect, with doxorubicin widely used but it application is impaired in its high concentration levels resulting in tissue injury, specifically, cardiotoxicity. However, advances in nanomedicine have paved the way for the search for an inorganic biomaterial with the potential to deliver doxorubicin (DOX) safely. Cockle shell-derived calcium carbonate (CaCO3) nanoparticle-loaded with DOX has shown a promising potential in the pre-clinical studies. Thus, this trial is aimed at exploring the effectiveness of DOX-loaded cockle shell-derived calcium carbonate aragonite nanoparticles (CS-CaCO3NP-DOX) on dogs with spontaneous tumours with aim of improving the overall survival rate and quality of life. A prospective single centre, non-blind open clinical trial of repeated doses of CS-CaCO3NP-DOX on dogs with solid tumours was performed. The primary and secondary endpoints were evaluated every three weeks for 15 weeks. There was no major adverse effect observed within the period on the vital parameters, haematological and biochemical profile associated with the formulation. Although, partial response and progressive cRECIST response were recorded in the two cases enrolled within the study period, however, production of osteoid matrix, inhibition of cell proliferation and induction of osteogenic cell death were observed 48 h after treatment. This preliminary finding shows that biogenic CS-CaCO3NP-DOX is potentially effective for treating bone cancer in dogs and improves the quality of life of dogs with solid tumours and further reveals the safety and anticancer efficiency of CS-CaCO3NP-DOX in dogs with solid tumours.

Evaluation of in vitro efficacy of docetaxel-loaded calcium carbonate aragonite nanoparticles (DTX-CaCO3NP) on 4T1 mouse breast cancer cell line.

Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5μg/mL and above had comparable cytotoxic effects with free DTX at 24h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72h. Fluorescence and apoptosis assay showed a higher (p<0.05) number of apoptotic cells in both free DTX and DTX-CaCO3NP groups. Cell cycle analysis showed cycle arrest at subG0 and G2/M phases in both treatment groups. SEM showed presence of cellular blebbing, while TEM showed nuclear fragmentation, apoptosis, and vacuolation in the treatment groups. Scratch assay showed lower (p<0.05) closure in both free DTX and DTX-CaCO3NP groups. The results from this study showed that DTX-CaCO3NP has similar anticancer effects on 4T1 cells as free DTX, and since it has a slow release rate, it is a more preferred substitute for free DTX.

Formulation of a Sustained Release Docetaxel Loaded Cockle Shell-Derived Calcium Carbonate Nanoparticles against Breast Cancer.

Here, we explored the formulation of a calcium carbonate nanoparticle delivery system aimed at enhancing docetaxel (DTX) release in breast cancer. The designed nano- anticancer formulation was characterized thorough X-ray diffraction (XRD), Fourier transformed infrared (FTIR), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) and Brunauer-Emmett-Teller (BET) methods. The nano- anticancer formulation (DTX- CaCO3NP) was evaluated for drug delivery properties thorough in vitro release study in human body simulated solution at pH7.4 and intracellular lysosomal pH4.8. Characterization revealed the successful synthesis of DTX- CaCO3NP, which had a sustained release at pH7.4. TEM showed uniformly distributed pleomorphic shaped pure aragonite particles. The highest entrapment efficiency (96%) and loading content (11.5%) were obtained at docetaxel to nanoparticles ratio of 1:4. The XRD patterns revealed strong crystallizations in all the nanoparticles formulation, while FTIR showed chemical interactions between the drug and nanoparticles with negligible positional shift in the peaks before and after DTX loading. BET analysis showed similar isotherms before and after DTX loading. The designed DTX- CaCO3NP had lower (p<0.05) cytotoxity against MCF-7 cells than DTX at 24h but comparable (p>0.05) effects at 48h and 72h. However, the DTX- CaCO3NP released less than 80% of bond DTX at 48 and 72h but showed comparable effects with free DTX. The results showed that the developed DTX- CaCO3NP released DTX slower at pH7.4 and had comparable cytotoxicity with free DTX at 48 and 72h in MCF-7 cells.