Pharmacosomes and Emulsomes: An Emerging Novel Vesicular Drug Delivery System

Novel drug delivery attempts to either sustain drug action at a predetermined rate, or by maintaining a relatively constant, effective drug level in the body with concomitant reduction of undesirable side effects. In vesicular drug delivery system drug binds covalently to the lipid molecule by which the drug release in a controlled manner and also drugs which are of hydrophilic or lipophilic nature can be delivered by using the vesicular drug delivery systems. The release of drug from the vesicles depends on the physicochemical characteristic of both the drug and carrier. Vesicular drug delivery system contains liposomes, niososmes, transferosomes, pharmacosomes, emulsomes, electrosomes, ethosomes etc. Pharmacosomes are amphiphilic phospholipids complexes of drugs bearing active hydrogen that bind to phospholipids. Like further vesicular systems pharmacosomes provide an effective method for delivery of drug directly to the site of infection, leading to minimization of drug toxicity with no adverse effects. They also decrease the cost of therapy by enhancing bioavailability of medication, particularly in case of poorly soluble drugs. Emulsomes is a novel lipoidal vesicular system with an inner solid fat core surrounded by a phospholipid bilayer. Emulsomal formulations composed of solid lipid core material and stimulated by cholesterol and soya lecithin. The drug is loaded accompanied by sonication to produce emulsomes of small size. This review discourse the concept of emulsome and pharmacosome drug delivery system, summarize the success of emulsomes and pharmacosomes for the delivery of small molecules, and special concentration has been paid to its formulation design, merits, biopharmaceutical aspects, stability aspects, and various different aspects associated to the drug delivery system including future aspects. Hence, pharmacosomes and emulsomes opens new challenges and opportunities for improved novel vesicular drug delivery system.


Introduction
In the past few decades, significant attention has been made on the development of novel drug delivery system (NDDS). The NDDS should ideally fulfil two conditions: Firstly, it should deliver the drug at a rate directed by the requirement of the body, over the period of treatment, secondly; it should channel the active system to the site of action. Conventional dosage forms as well as prolonged release dosage forms are unable to meet none of these. Novel drug delivery efforts to either sustain drug activity at a predetermined rate, or by maintaining a relatively constant, effective drug level in the body with concomitant reduction of undesirable side effects. spheroid structures consist of lipid molecules assembled into bilayers, Because of their capacity to carry a number of drugs, vesicular delivery systems have been widely investigated for their prospective application in pharmaceutics such as drug delivery for drug targeting, for controlled release, or for increasing solubility [5,10].

Pharmacosomes
Pharmacosomes are portion of the novel drug delivery system. They were first introduced by vaizoglu and Speriser in 1968.
Pharmacosomes are determined as the colloidal dispersions, drugs covalently bound to the lipids, and may exists as ultra-fine vesicular, micellar, or hexagonal aggregates, on the basis of the chemical structure of the drug-lipid complex. The system is composed by linking a drug (pharmakon) to a carrier (soma), so they termed as "Pharmacosomes" [6,5]. After absorption, their velocity of deterioration into active drug molecule depends to a great extent on the size and functional groups of drug molecule, the chain length of the lipids and the spacer [8,3] (Figure 1). f. The prodrug amalgamates have both hydrophilic and lipophilic properties, so they acquire amphiphilic nature and therefore found to decrease the interfacial tension, and mesomorphic behavior at elevated concentrations [7,9].

Advantages of Pharmacosomes [3,7,10]
Compared to other categories of lipid based delivery systems, pharmacosomes exhibit better results in many ways.
a. The drug-lipid complex depends upon the phase transition temperature but independent on rate of release as it is covalently bounded to the lipid.

Disadvantages of Pharmacosomes [7,11]
• Water insoluble drugs are encapsulated relatively in a less hydrophobic region within membrane bilayer rather than relatively large surface area.
• Synthesis of a compound depends on its amphiphilic nature.
• Preffered surface and bulk interaction of lipids with drugs.
• Required covalent bonding to protect the leakage of drugs.
• The storage of pharmacosomes undergoes fusion and aggregation and also chemical hydrolysis. The physicochemical characters of the drug-lipid complex affect the stability of pharmacosomes. (Figure 2).

Lipids:
• Phospholipids are the major components of biological membrane; majorly two types of phospholipids are used namely phosphoglycerides and sphingolipids.
• The most common kind of phospholipids is Phosphotidylecholine moiety.
• Phosphotidylecholine is an amphiphilic molecule in which a glycerol bridges joints a pair of hydrophobic acylhydrocarbon chains with hydrophilic polar head group phosphocholine [7].

Hand Shaking Method/Solvent Evaporation Method
Mixture of drug and lipid is dissolved in a volatile organic solvent. Thereafter solvent is evaporated using rotatory evaporator in round bottom flask which leaves a thin film of solid mixture deposited on the walls of flask. The dried film hydrates with aqueous medium and readily gives a vesicular suspension [3,14].

Ether Injection Method
The drug-lipid complex is dissolved in specified volume of ether. Then the above mixture is slowly injected into a heated buffer solution, resulting in the formation of the vesicles. The nature of vesicle especially the shape depends on the concentration. The variety of structures may be formed that are, round, cylindrical, disc, cubic, or hexagonal type depending on the amphiphilic state [7,15].

Anhydrous Co-Solvent Lyophilization Method
First of all drug and phospholipids are dissolved in solution of dimethyl sulfoxide containing glacial acetic acid. Then mixture is agitated to get clear liquid and then freeze-dried overnight at condenser temperature. The resultant complex is flushed with nitrogen and stored at 4°C [3,16].

Supercritical Fluid Process
Drug and lipid complex are dissolved in a supercritical fluid of CO 2 , then it is mix into nozzle mixing chamber [3,7].

Evaluation of Pharmacosomes
i.
Complex determination: Using correlation spectrum the formation of both conjugate and complex can be contingent upon inspecting with that of discrete constituents and with their mixture using FTIR spectrum [17].
ii. Surface morphology: The surface morphology can be shaking at a temperature of 37°C for 24hrs. Then both the layers will be separated and samples were analyzed using HPLC or UV spectrophotometer [7,18].
v. Differential scanning calorimetry (DSC): This thermal analytical technique is used to determine the drug-excipients compatibility or interactions. The interaction can be concluded by the elimination endothermic peaks, appearance of peaks and change in peak shape and its onset, peak temperature/melting point and relative peaks area or enthalpy [3] vi. X-ray power diffraction (XRPD): It is performed to detremine the degree of crystallinity by using the relative integrated intensity of reflection peaks . The itegrated intensity is specified by the area under curves of the XRPD patterns and it represents the specimen charetristics [19,3]. is the increased efficiency in terms of staffing as a consequence of reduction in number of steps [7,21].

Applications of Pharmacosomes [3,7]
 Pharmacosomes possess better stability and shelf life compared to other vesicular drug delivery systems.
 Absorption and permeation of the drug can be enhanced formulating in to pharmacosomes.


The transportation of drug across the biological membranes is due to the vesicular formation as they have the capacity to interact with the membranes, due to their transitions from vesicle to micelle by altering the transition temperature.

Advantages of Emulsomes [26,27]
• Emulsomes protect drug from harsh gastric environment of stomach before oral administration because the drug is surroundedby the triglyceride lipid core. This hypothesis could be supported by the fact that gastric pH and gastric enzymes are unable to hydrolyze triglycerides.

Mechanism of Emulsomes Absorption
Emulsomes have structural similarity with the chylomicrons (natural lipoprotein of the body) and therefore expected to mimic these lipoproteins in behavior. These diminutive lipids like particles are frequently taken through endogenous lipid absorption mechanism through enterocytes of GIT tract [28].
Intestinal absorption of long-chain triglyceride from enterocytes is a complex incident that includes the co-ordination of synthesis of apolipoproteins and lipids and their intracellular assembly into mature lipid-containing particles [26].  allows forming vesicles of larger size and hence large area exposed to the dissolution medium [26,27].

Materials Uses References
Triglycerides Used as hydrophobic lipid core, Lipids with low HLB value provides sustain released formulation.

35,36
Cholesterol Incorporation of cholesterol influence vesicles stability, excessive cholesterol leads to un-stability of the formulation. 37 Soya lecithin Bilayer sheets, micelles or lamellar structures and also increases the entrapment efficiency. 32 Sterylamine Impart positive charge for target delivery and raised the zeta potential of formulation. 37

Antioxidant
Protect the lipids from oxidation or rancidity. 31

Surfactants
Provide the highest entrapment for the drug. 38   Leishmaniasis:Leishmaniasis is a disease in which a parasite of the genus Leishmania invades the cells of the liver and spleen.

Applications of Emulsomes
Frequently prescribed drugs for the treatment are derivatives of antimony (antimonials), which in high concentrations can cause cardiac, liver, and kidney damage. Use of emulsome in tests conducted showed that it was possible to administer higher levels of the drug without triggering the side effects, and thus allowed greater efficacy in treatment [26,40].