Pharmacosomes- An Immense Potential Vesicular Constructs

Selvaraju K.*, Vengadesh Prabhu K., Karthick K., Padma Preetha J. and Arul Kumaran K.S.G.

KMCH College of Pharmacy, Coimbatore-641048.Tamilnadu, India.

ABSTRACT:

Various Colloidal vesicular system employed in controlled and targeted delivery system are liposomes, Niosomes, Virosomes, Immuuoliposomes, Transferosomes and Pharmacosomes. Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids and may exist as ultrafine vesicular, micellar or hexagonal aggregates, depending on the chemical structure. Because the system is formed by linking a drug (pharmakon) to a carrier (soma) they are called pharmacosomes. They are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. They are bearing unique advantages over liposomes and niosomes vesicles that can pass through biomembranes efficiently. They potentially delivery the drugs directly to the site of infection, leading to reduction of drug toxicity with no adverse effect.

KEYWORDS: Pharmacosomes, amphiphilic, controlled and targeted drug delivery system.

INTRODUCTION:

In the past few decades, considerable attention has been focused on the development of new drug delivery system (NDDS). The NDDS should ideally fulfill two prerequisites. Firstly, it should deliver the drug at a rate directed by the needs of the body, over the period of treatment. Secondly, it should channel the active entity to the site of action. Conventional dosage forms including prolonged release dosage forms, are unable to meet none of these. At present, no available drug delivery system behaves ideally, but sincere attempts have been made to achieve them through various novel approaches in drug delivery¹. Different types of pharmaceutical carriers are present. They are - particulate, polymeric, macromolecular, and cellular carrier. Particulate type carrier also known as a colloidal carrier system, includes lipid particles (low and high density lipoprotein-LDL and HDL, respectively), microspheres, nanoparticles, polymeric micelles and vesicular like liposomes, niosomes pharmacosomes, virosomes^2,3,4,5.

In recent years, vesicles have become the vehicle of choice in drug delivery. Lipid vesicles were found to be of value in immunology, membrane biology, diagnostic techniques, and most recently, genetic engineering⁶^{, 7}.

They are defined as colloidal dispersion of drugs covalently bound to lipids and may exist as ultrafine vesicular, micellar or hexagonal aggregated, depending on the chemical structure of drug lipid complex. If the hydrophilic drug is conjugated with lipophilic promoiety the prodrug becomes amphiphilic. Any drug possessing free carboxyl group can be esterified to the hydroxyl group of the lipid, with or without spacer chain. Since the system is formed by linking of drug (pharma kon) to carrier word originally coined⁸.

The system was developed as alternative to liposomes, which show low entrapment efficiency and drug leakage during storage for hydrophilic drug .

Difference between Pharmacosomes, Niosomes and Transferosomes:

Niosomes a non-ionic surfactant based vesicles formed by the self assembly of non-ionic amiphiles in aqueous medium resulting in closed aqueous bilayer structure. To have spontaneous formtion of this bilayer structure; physical agitation (Sort of energy) should be applied. Pharmacosomes are colloidal dispersion of a drug covalently bound to a lipid result in ultrafine vesicular, micellar or hexagonal aggregates according to the nature of the drug-lipid complex.

Like liposomes, aqueous suspension of niosomes may exhibit aggregation, fusion, leaching or hydrolysis of entrapped drugs, thus limiting the shelf- life of niosomes dispersion. Niosome preparation is time-consuming, requires specialized equipment, and is inefficient, particularly if smaller quantities are required for particular application or dose.

Transfersomes are chemically unstable because of their predisposition to oxidative degradation, Lack of purity of the natural phospholipids comes in the way of adoption of transfersomes as drug delivery vehicles and Transfersomes formulations are expensive to prepare. To overcome this problem pharmacosomes have been evolved.

MERITS OF PHARMACOSOMES:

1. Suitable for both hydrophilic and liphophilic drugs.

2. High and predetermine entrapment efficiency

3. Due to their amphiphilic behavior, the system allowed, a multiple transfer through the lipophilic membrane system or tissue, through cellular walls piggy back endocytosis and exocytosis.

4. Improves bioavailability especially with case of poorly water soluble drugs.

5. Reduction in adverse effects and toxicity

6. Reduced cost of therapy.

7. They can be given orally, topically, extra or intra vascularly

PREPARATION OF PHARMACOSOMES:

The following two methods have been employed for the preparation of pharmacosomes.

(i) Hand Shaking method (ii) Ether injection method

In hand shaking method, the dried film of the drug lipid complex deposited in a round bottom flask up on hydration with aqueous medium readily gives vesicular suspension. In ether injection method, organic solution of drug lipid complex was injected slowly into the hot aqueous medium, where in the vesicles’ were readily formed.

Characterization of Pharmacosomes:

The prepared prodrug are generally characterized for their structural conformation by IR, NMR, Spectrophotometry, thin layer chromatography (TLC), Melting point determination, partition coefficient, surface tension and prodrug hydrolysis. Link other vesicular systems, pharmacosomes are characterized for different attributes such as size and size distribution NMR, Spectroscopy, entrapment efficiency, in vitro release rate, stability study etc., The approach has successfully improved the therapeutic performance of various drugs ie. Pindolol maleate, bupranolol , taxol , acyclovir , diclofenac.

Pindolol was as synthesized from glycerol monostereate ester of weak bases, via succenic acid and isolated maleate salt as two isomer. This prodrug having structural similarity with lysolecithin reduced interfacial tension between benzene/ water and opalescent vesicular dispersion could be obtained by the film method and ether injection method.

Buprenolol hydrochloride was synthesized the prodrug consisting of beta blockers Buprenolol which is covalently linked to 1,3-dipalmitoryl-2-succinyl-glycerol.the resulting prodrug was amphipathic and dispersed readily in water above 30⁰ C forming a smectic lamellar phase. the dispersion similar to charged phospholipids showed continuous swelling with increasing water content and so in excess water region, the thermodynamically most stable structure was the unilamelllar vesicles while oligometric vesicles also formed¹². Compared the effect of diglyceride prodrug on interfacial tension, with the effect produced by a standard detergent dodecylamine hydrochloride, and observed similar effect on lowering of surface tension . Above the critical micelle concentration (CMC), the prodrug exhibits mesomorphic lyotropic behavior, and assembles in supramolecular structures. The prepared prodrugs are generally characterized for their structural conformation (by IR, NMR spectrophotometry, thin layer chromatography (TLC), melting point determination), partition coefficient, surface tension, and prodrug hydrolysis. Hand-shaking method and ether injection method, have been utilized for preparing vesicles. In hand-shaking method, the dried film of the drug-lipid complex (with or without egg lecithin) deposited in a round bottom flask upon hydration with aqueous medium, readily gives a vesicular suspension. In ether injection method, organic solution of the drug-lipid complex, was injected slowly into the hot aqueous medium, wherein the vesicles are readily formed¹⁰

Taxol Steve has synthesized and patented a drug conjugated covalently attached to a fatty acid chain of phospholipid, glyceride, ceramide or 1,2-diacyloxypropan-3-amine.the linkage between therapeutic agent and lipid is one which can be cleaved invivo¹¹.

Acyclovir: The lipid prodrug acyclovir diphosphate dimyristoyl glycerol forms liposomes and provides substancial activity against herpes simplex virus, acyclovir resistant strains of herpes simplex virus as compared to free acyclovir when tested in a rabbit model of herpes simplex virus -1 retinites¹².

Diclofenac is poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80%) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) and in vitro dissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity¹³.

Pharmacosomes bearing unique advantages over liposome and niosome vesicles, have come up as potential alternative to conventional vesicles. The system, yet requires greater efforts towards investigating the non-bilayer phases, and exploring the mechanism of action. Furthermore, the effect of covalent linkages and addition of spacer group on rate of in vivo hydrolysis and subsequent pharmacokinetics is to be exhaustively studied, in order to exploit more advantages of this system. Like other vesicular drug delivery systems, pharmacosomes, on storage, undergo fusion and aggregation, as well chemical hydrolysis¹⁴.

CONCLUSION:

Pharmacosomes, the novel drug carrier play an important role in the selective targeting and the controlled delivery of various drugs. Similar to other vesicular system pharmacosomes provide an efficient method for delivery of drug directly to the site of infection, leading to reduction of drug toxicity. Pharmacosomes may be developed for drugs with poor bioavailability and GI side effects, pharmacosomes of phyto constituents may also be developed for improving their aqueous solubility and lipophilicity and hence improved bioavailability.

ACKNOWLEDGMENT:

We express our sincere thanks to the Dr. Nalla G. Pallanisamy, Chairman and Dr. Thavamani D. Palaniswami, Managing trustee, of Kovai Medical Center Research and Educational Trust and Principal, KMCH College of pharmacy, Coimbatore, for giving the facilities and encouragement to carry out this work.

REFERENCE:

1. Li VHK, Robinson JR and Lee VHL, Fundamentals and Applications. Controlled Drug Delivery. 1987; 29: 7.

2. Goldberg EP, Eds., In: Targeted Drugs. 2nd Edn., Wiley, New York. 1983; 312.

3. Gregoriadis, G., Treatment of gaucher's disease with liposome-entrapped glucocerebroside: β-glucosidase. Nature. 1977; 265: 407.

4. Poste G, Kirsch R and Koestler T, In: Gregoriadis, G. Eds; Liposomes Technology. CRC Press Inc., Baco Raton. Fl, 1983; 13:29.

5. Poznansky MJ, Juliano RL, Biological approaches to the controlled delivery of drugs: a critical review. Pharmacol Rev. 1984; 36(4): 277–336.

6. Ogihara-Umeda I, Sasaki T, Toyama H, Oda K, Senda M and Nishigori H, Cancer Detect Prev. 1997; 21(6): 490 .

7. Park JW, Hong K, Kirpotin DB and Benz CC, Immunoliposomes for cancer treatment. Adv. Pharmacol. 1997; 40: 399.

8. Vaizoglu O and Speiser PP, Pharmacosomes – A novel drug delivery system. Acta Pharm. Suec. 1986; 23: 163-172.

9. Jain NK. Advances in controlled and novel drug delivery. CBS publishers, New Delhi, India. 2008; 273- 278.

10. Mantelli S, Speiser P and Hauser H, phase behavior of a diglyceride prodrug: spontaneous formation of unilamellar vesicles. Chem. phys. Lipids.1985; 37: 329-43.

11. Steve A, Lipophilic drug derivatives for use in liposomes. U.S.Patent USS, 534, 499 (c1 s14-24 A61 k31/70) 1996;11.

12. Taskintuna I, Banker AS, Flores-Aguilar, Lynn M, Freeman WR and Retina, Evaluation of novel lipid prodrug for intraocular drug delivery: effect of acyclovir diphosphate dimyristoyl glycerol in a rabbit model with herpes simplex virus 21 retinitis. Retina. 1997;17: 57-64.

13. Ajay semalty, Mona Semalty, Devendra sing, Development and physic chemical evaluation of pharmacosomes of diclofenac. Acta Pharma., 2009; 59: 335 – 344.

14. Biju SS, Sushama Talegaonkar, Mishra PR and Khar Rk, Vesicular systems: An overview. Ind. Jour. Pharm. Sci. 2006; 68(2): 141-153.

Received on 28.03.2011

Accepted on 14.04.2011

Research Journal of Pharmaceutical Dosage Forms and Technology. 3(3): May-June 2011, 84-86

S.NO	LIPOSOMES	PHARMACOSOMES
1.	Incorporation of drug in the aqueous or lipid phase of a mixture of lipid where the physicochemical properties of the carrier and release of drug will be function of different lipids used.	Covalent binding of a drug to a lipid where the resulting compound is the carrier and the active compound at the same time. The physicochemical properties depend on drug as well as lipid. Well as the lipid.
2.	Loss of drug through leaking	No leakage, loss of drug by hydrolysis is possible.
3.	Release of drug by diffusion mechanism	Release of drug by hydrolysis (Including enzymatic)
4.	Physical stability is relatively good	Depends on the pysico chemical properties of the drug lipid complex.